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2000
Volume 21, Issue 2
  • ISSN: 1573-403X
  • E-ISSN: 1875-6557

Abstract

The coexistence of cancer and heart disease, both prominent causes of illness and death, is further exacerbated by the detrimental impact of chemotherapy. Anthracycline-induced cardiotoxicity is an unfortunate side effect of highly effective therapy in treating different types of cancer; it presents a significant challenge for both clinicians and patients due to the considerable risk of cardiotoxicity. Despite significant progress in understanding these mechanisms, challenges persist in identifying effective preventive and therapeutic strategies, rendering it a subject of continued research even after three decades of intensive global investigation. The molecular targets and signaling pathways explored provide insights for developing targeted therapies, emphasizing the need for continued research to bridge the gap between preclinical understanding and clinical applications. This review provides a comprehensive exploration of the intricate mechanisms underlying anthracycline-induced cardiotoxicity, elucidating the interplay of various signaling pathways leading to adverse cellular events, including cardiotoxicity and death. It highlights the extensive involvement of pathways associated with oxidative stress, inflammation, apoptosis, and cellular stress responses, offering insights into potential and unexplored targets for therapeutic intervention in mitigating anthracycline-induced cardiac complications. A comprehensive understanding of the interplay between anthracyclines and these complexes signaling pathways is crucial for developing strategies to prevent or mitigate the associated cardiotoxicity. Further research is needed to outline the specific contributions of these pathways and identify potential therapeutic targets to improve the safety and efficacy of anthracycline-based cancer treatment. Ultimately, advancements in understanding anthracycline-induced cardiotoxicity mechanisms will facilitate the development of more efficacious preventive and treatment approaches, thereby improving outcomes for cancer patients undergoing anthracycline-based chemotherapy.

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References

  1. GhigoA. LiM. HirschE. New signal transduction paradigms in anthracycline-induced cardiotoxicity.Biochim. Biophys. Acta Mol. Cell Res.201618637)(7 Pt B1916192510.1016/j.bbamcr.2016.01.02126828775
    [Google Scholar]
  2. MorelliM.B. BongiovanniC. Da PraS. MianoC. SacchiF. LauriolaM. D’UvaG. Cardiotoxicity of anticancer drugs: Molecular mechanisms and strategies for cardioprotection.Front. Cardiovasc. Med.2022984701210.3389/fcvm.2022.84701235497981
    [Google Scholar]
  3. BrayF. LaversanneM. CaoB. VargheseC. MikkelsenB. WeiderpassE. SoerjomataramI. Comparing cancer and cardiovascular disease trends in 20 middle- or high-income countries 2000–19: A pointer to national trajectories towards achieving sustainable development goal target 3.4.Cancer Treat. Rev.202110010229010.1016/j.ctrv.2021.10229034536729
    [Google Scholar]
  4. BehlT. BungauS. KumarK. ZenginG. KhanF. KumarA. KaurR. VenkatachalamT. TitD.M. VesaC.M. BarsanG. MosteanuD.E. Pleotropic effects of polyphenols in cardiovascular system.Biomed. Pharmacother.202013011071410.1016/j.biopha.2020.11071434321158
    [Google Scholar]
  5. AdhikariA. AsdaqS.M.B. Al HawajM.A. ChakrabortyM. ThapaG. BhuyanN.R. ImranM. AlshammariM.K. AlshehriM.M. HarshanA.A. AlanaziA. AlhazmiB.D. SreeharshaN. Anticancer drug-induced cardiotoxicity: Insights and pharmacogenetics.Pharmaceuticals2021141097010.3390/ph1410097034681194
    [Google Scholar]
  6. GheorgheG. TothP.P. BungauS. BehlT. IlieM. Pantea StoianA. BratuO.G. BacalbasaN. RusM. DiaconuC.C. Cardiovascular risk and statin therapy considerations in women.Diagnostics.202010748310.3390/diagnostics1007048332708558
    [Google Scholar]
  7. JainD AronowW Cardiotoxicity of cancer chemotherapy in clinical practice.Hosp Pract20194716–15
    [Google Scholar]
  8. FlorescuM. CintezaM. VinereanuD. Chemotherapy-induced Cardiotoxicity.Maedica201381596724023601
    [Google Scholar]
  9. SishiB.J.N. Autophagy upregulation reduces doxorubicin-induced cardiotoxicity.Autophagy: Cancer, other pathologies, inflammation, immunity, infection, and aging.Chapter 10 HayatM.A. [Internet]AmsterdamAcademic Press2015157173https://www.sciencedirect.com/science/article/pii/B9780128010334000102
    [Google Scholar]
  10. ZamoranoJ.L. LancellottiP. Rodriguez MuñozD. AboyansV. AsteggianoR. GalderisiM. HabibG. LenihanD.J. LipG.Y.H. LyonA.R. Lopez FernandezT. MohtyD. PiepoliM.F. TamargoJ. TorbickiA. SuterT.M. ESC Scientific Document Group 2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines.Eur. Heart J.201637362768280110.1093/eurheartj/ehw21127567406
    [Google Scholar]
  11. DanesiR. FogliS. GennariA. ConteP. Del TaccaM. Pharmacokinetic-pharmacodynamic relationships of the anthracycline anticancer drugs.Clin. Pharmacokinet.200241643144410.2165/00003088‑200241060‑0000412074691
    [Google Scholar]
  12. YehE.T.H. BickfordC.L. Cardiovascular complications of cancer therapy: Incidence, pathogenesis, diagnosis, and management.J. Am. Coll. Cardiol.200953242231224710.1016/j.jacc.2009.02.05019520246
    [Google Scholar]
  13. NebigilC.G. DésaubryL. Updates in anthracycline-mediated cardiotoxicity.Front. Pharmacol.20189126210.3389/fphar.2018.0126230483123
    [Google Scholar]
  14. GianniL. HermanE.H. LipshultzS.E. MinottiG. SarvazyanN. SawyerD.B. Anthracycline cardiotoxicity: From bench to bedside.J. Clin. Oncol.200826223777378410.1200/JCO.2007.14.940118669466
    [Google Scholar]
  15. PackardR.R.S. YangE.H. Editorial: Novel mechanisms, imaging approaches, and management strategies for anthracycline-induced cardiotoxicity.Front. Cardiovasc. Med.20239110907810.3389/fcvm.2022.110907836684589
    [Google Scholar]
  16. FazioS. PalmieriE.A. FerravanteB. Bon ÈF. BiondiB. SaccàL. Doxorubicin‐induced cardiomyopathy treated with carvedilol.Clin. Cardiol.1998211077777910.1002/clc.49602110179789703
    [Google Scholar]
  17. CarrascoR. CastilloR.L. GormazJ.G. CarrilloM. ThavendiranathanP. Role of oxidative stress in the mechanisms of anthracycline‐induced cardiotoxicity: Effects of preventive strategies.Oxid. Med. Cell. Longev.202120211886378910.1155/2021/886378933574985
    [Google Scholar]
  18. VenkateshP. KasiA. Anthracyclines.In: StatPearls.2024Treasure Island, FLStatPearls Publishinghttp://www.ncbi.nlm.nih.gov/books/NBK538187/
    [Google Scholar]
  19. ShandilyaM. SharmaS. DasP.P. CharakS. ShandilyaM. SharmaS. DasP.P. CharakS. Molecular-level understanding of the anticancer action mechanism of anthracyclines.Adv Precis Med Oncol2020https://www.intechopen.com/chapters/73668
    [Google Scholar]
  20. Martins-TeixeiraM.B. CarvalhoI. Antitumour anthracyclines: Progress and perspectives.ChemMedChem2020151193394810.1002/cmdc.20200013132314528
    [Google Scholar]
  21. BoltonJ.L. DunlapT. Formation and biological targets of quinones: Cytotoxic versus cytoprotective effects.Chem. Res. Toxicol.2017301133710.1021/acs.chemrestox.6b0025627617882
    [Google Scholar]
  22. VisoneV. SzabóI. PeruginoG. HudeczF. BánócziZ. ValentiA. Topoisomerases inhibition and DNA binding mode of daunomycin–oligoarginine conjugateJ Enzyme Inhib Med Chem20243511363.1371
    [Google Scholar]
  23. MattioliR. IlariA. ColottiB. MoscaL. FaziF. ColottiG. Doxorubicin and other anthracyclines in cancers: Activity, chemoresistance and its overcoming.Mol. Aspects Med.202393101205https://www.sciencedirect.com/science/article/pii/S009829972300045610.1016/j.mam.2023.10120537515939
    [Google Scholar]
  24. QunT. ZhouT. HaoJ. WangC. ZhangK. XuJ. WangX. ZhouW. Antibacterial activities of anthraquinones: Structure–activity relationships and action mechanisms.RSC Med. Chem.202314814461471https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10429894/10.1039/D3MD00116D37593578
    [Google Scholar]
  25. KhasrawM. BellR. DangC. Epirubicin: Is it like doxorubicin in breast cancer? A clinical review.Breast201221214214910.1016/j.breast.2011.12.01222260846
    [Google Scholar]
  26. EdwardsonD. NarendrulaR. ChewchukS. Mispel-BeyerK. MapletoftJ. ParissentiA. Role of drug metabolism in the cytotoxicity and clinical efficacy of anthracyclines.Curr. Drug Metab.2015166412426https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5398089/10.2174/138920021688815091511203926321196
    [Google Scholar]
  27. AlossK. HamarP. Recent preclinical and clinical progress in liposomal doxorubicin.Pharmaceutics2023153893https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10054554/10.3390/pharmaceutics1503089336986754
    [Google Scholar]
  28. ThornC.F. OshiroC. MarshS. Hernandez-BoussardT. McLeodH. KleinT.E. AltmanR.B. Doxorubicin pathways.Pharmacogenet. Genomics2011217440446https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3116111/10.1097/FPC.0b013e32833ffb5621048526
    [Google Scholar]
  29. DouediS. CarsonM.P. Anthracycline medications (doxorubicin).In: StatPearls.InternetTreasure Island, FLStatPearls Publishing2024http://www.ncbi.nlm.nih.gov/books/NBK551633/
    [Google Scholar]
  30. ChatterjeeK. ZhangJ. HonboN. KarlinerJ.S. Doxorubicin cardiomyopathy.Cardiology20101152155162https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2848530/10.1159/00026516620016174
    [Google Scholar]
  31. SaleemT. KasiA. Daunorubicin.In: StatPearls.2024Treasure Island, FLStatPearls Publishinghttp://www.ncbi.nlm.nih.gov/books/NBK559073/
    [Google Scholar]
  32. PresantC.A. ScolaroM. KennedyP. BlayneyD.W. FlanaganB. LisakJ. PresantJ. Liposomal daunorubicin treatment of HIV-associated Kaposi’s sarcoma.Lancet199334188551242124310.1016/0140‑6736(93)91147‑E8098393
    [Google Scholar]
  33. SamuelsL.D. NewtonW.A.Jr HeynR. Daunorubicin therapy in advanced neuroblastoma.Cancer197127483183410.1002/1097‑0142(197104)27:4<831::AID‑CNCR2820270412>3.0.CO;2‑Z5574074
    [Google Scholar]
  34. KantarjianH.M. TalpazM. KontoyiannisD. GuttermanJ. KeatingM.J. EsteyE.H. O’BrienS. RiosM.B. BeranM. DeisserothA. Treatment of chronic myelogenous leukemia in accelerated and blastic phases with daunorubicin, high-dose cytarabine, and granulocyte-macrophage colony-stimulating factor.J. Clin. Oncol.199210339840510.1200/JCO.1992.10.3.3981740679
    [Google Scholar]
  35. PloskerG.L. FauldsD. Epirubicin.Drugs199345578885610.2165/00003495‑199345050‑000117686469
    [Google Scholar]
  36. AldersonD. CunninghamD. NankivellM. BlazebyJ.M. GriffinS.M. CrellinA. GrabschH.I. LangerR. PritchardS. OkinesA. KrysztopikR. CoxonF. ThompsonJ. FalkS. RobbC. StenningS. LangleyR.E. Neoadjuvant cisplatin and fluorouracil versus epirubicin, cisplatin, and capecitabine followed by resection in patients with oesophageal adenocarcinoma (UK MRC OE05): An open-label, randomised phase 3 trial.Lancet Oncol.201718912491260https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5585417/10.1016/S1470‑2045(17)30447‑328784312
    [Google Scholar]
  37. NeriB. CiniG. DoniL. FulignatiC. TurriniM. PantaloneD. MiniE. De Luca CardilloC. FiorettoL.M. RibeccoA.S. MorettiR. ScatizziM. ZocchiG. QuattroneA. Weekly gemcitabine plus Epirubicin as effective chemotherapy for advanced pancreatic cancer: A multicenter phase II study.Br. J. Cancer2002875497501https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2376146/10.1038/sj.bjc.660048212189543
    [Google Scholar]
  38. GanzinaF. Di PietroN. MagniO. Clinical toxicity of 4′-epi-doxorubicin (epirubicin).Tumori198571323324010.1177/0300891685071003043861022
    [Google Scholar]
  39. SurjusheA. VasaniR. MedhekarS. ThakreM. SapleD.G. Hand-foot syndrome due to capecitabine.Indian J. Dermatol.20085314344https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784591/10.4103/0019‑5154.3974719967024
    [Google Scholar]
  40. FukushimaT. UedaT. UchidaM. NakamuraT. Action mechanism of idarubicin (4-demethoxydaunorubicin) as compared with daunorubicin in leukemic cells.Int. J. Hematol.19935721211308494991
    [Google Scholar]
  41. OwattanapanichW. OwattanapanichN. KungwankiattichaiS. UngprasertP. RuchutrakoolT. Efficacy and toxicity of idarubicin versus high-dose daunorubicin for induction chemotherapy in adult acute myeloid leukemia: A systematic review and meta-analysis.Clin. Lymphoma Myeloma Leuk.20181812814821.e310.1016/j.clml.2018.08.00830241991
    [Google Scholar]
  42. PoglianiE.M. BaldicchiL. PioltelliP. MiccolisI.R. MangiagalliM. CorneoG.M. Idarubicin in combination with cytarabine and VP-16 in the treatment of post myelodysplastic syndrome acute myeloblastic leukemia (MDS-AML).Leuk. Lymphoma1995195-647347710.3109/104281995091122078590849
    [Google Scholar]
  43. SherifH.A. MagdyA. ElshesheniH.A. RamadanS.M. RashedR.A. Treatment outcome of doxorubicin versus idarubicin in adult acute myeloid leukemia.Leuk. Res. Rep.202116100272https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8517376/10.1016/j.lrr.2021.10027234692402
    [Google Scholar]
  44. FoxE.J. Mechanism of action of mitoxantrone.Neurology20046312)(Suppl. 6S15S1815623664
    [Google Scholar]
  45. AlbertsD.S. PengY.M. BowdenG.T. DaltonW.S. MackelC. Pharmacology of mitoxantrone: Mode of action and pharmacokinetics.Invest. New Drugs19853210110710.1007/BF001741564040505
    [Google Scholar]
  46. BerryW. DakhilS. ModianoM. GregurichM. AsmarL. Phase III study of mitoxantrone plus low dose prednisone versus low dose prednisone alone in patients with asymptomatic hormone refractory prostate cancer.J. Urol.200216862439244310.1016/S0022‑5347(05)64163‑812441935
    [Google Scholar]
  47. ArmitageJO The role of mitoxantrone in non-Hodgkin’s lymphomaOncology2002164490502
    [Google Scholar]
  48. JiaoD. YangB. ChenJ. WangC. JinL. ZhaoW. GaoX. WangH. LiJ. ZhaoH. WuD. FanZ. WangS. LiuZ. WangY. WuJ. Efficacy and safety of mitoxantrone hydrochloride injection for tracing axillary sentinel nodes in breast cancer: A self-controlled clinical trial.Front. Oncol.202212914057https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9217178/10.3389/fonc.2022.91405735756664
    [Google Scholar]
  49. ChangA. A case of mitoxantrone extravasation.J. Oncol. Pharm. Pract.20202651270127310.1177/107815521989373631902285
    [Google Scholar]
  50. GoldbergI.P. LichtbrounB. SingerE.A. GhodoussipourS. Pharmacologic therapies for non-muscle invasive bladder cancer: Current and future treatments.Arch. Pharmacol. Ther.2022411322https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9431226/[Internet].36051251
    [Google Scholar]
  51. OnrustS.V. LambH.M. Valrubicin.Drugs aging1999151697510.2165/00002512‑199915010‑0000610459733
    [Google Scholar]
  52. DinneyC.P.N. GreenbergR.E. SteinbergG.D. Intravesical valrubicin in patients with bladder carcinoma in situ and contraindication to or failure after bacillus Calmette-Guérin.Urol. Oncol.20133181635164210.1016/j.urolonc.2012.04.01022575238
    [Google Scholar]
  53. MurzynA. OrzełJ. ObajtekN. MrózA. MiodowskaD. BojdoP. GąsiorkiewiczB. Koczurkiewicz-AdamczykP. PiskaK. PękalaE. Aclarubicin: contemporary insights into its mechanism of action, toxicity, pharmacokinetics, and clinical standing.Cancer Chemother. Pharmacol.202410.1007/s00280‑024‑04693‑138965080
    [Google Scholar]
  54. ZhengS. ZhouS. QiaoG. YangQ. ZhangZ. LinF. MinD. TangL. LiH. SunY. ZhaoH. ShenZ. YaoY. Pirarubicin-based chemotherapy displayed better clinical outcomes and lower toxicity than did doxorubicin-based chemotherapy in the treatment of non-metastatic extremity osteosarcoma.Am. J. Cancer Res.201451411422https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4300710/[Internet].25628949
    [Google Scholar]
  55. El-KawyO.A. AbdelazizG. Preparation, characterization and evaluation of [125I]-pirarubicin: A new therapeutic agent for urinary bladder cancer with potential for use as theranostic agent.Appl. Radiat. Isot.2022179110007https://www.sciencedirect.com/science/article/pii/S096980432100402410.1016/j.apradiso.2021.11000734736111
    [Google Scholar]
  56. BaiM. PanT. ZhouC. LiM. ChenJ. ZengZ. ZhuD. WuC. JiangZ. LiZ. HuangM. Transarterial chemoembolization with pirarubicin-eluting microspheres in patients with unresectable hepatocellular carcinoma: Preliminary results.J. Interv. Med.2019226977https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8562294/10.1016/j.jimed.2019.09.00534805876
    [Google Scholar]
  57. SteinherzL.J. WexlerL.H. The prevention of anthracycline cardiomyopathy.Prog. Pediatr. Cardiol.19988397108https://www.sciencedirect.com/science/article/pii/S105898139800006X10.1016/S1058‑9813(98)00006‑X
    [Google Scholar]
  58. YanH. WangP. YangF. ChengW. ChenC. ZhaiB. ZhouY. Anticancer therapy-induced adverse drug reactions in children and preventive and control measures.Front. Pharmacol.2024151329220https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1329220/full10.3389/fphar.2024.132922038425652
    [Google Scholar]
  59. YamaokaT. HanadaM. IchiiS. MorisadaS. NoguchiT. YanagiY. Uptake and intracellular distribution of amrubicin, a novel 9-amino-anthracycline, and its active metabolite amrubicinol in P388 murine leukemia cells.Jpn. J. Cancer Res.1999906685690https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5926123/10.1111/j.1349‑7006.1999.tb00801.x10429662
    [Google Scholar]
  60. KurataT. OkamotoI. TamuraK. FukuokaM. Amrubicin for non-small-cell lung cancer and small-cell lung cancer.Invest. New Drugs200725549950410.1007/s10637‑007‑9069‑017628745
    [Google Scholar]
  61. IkedaT. TakemotoS. SenjuH. GyotokuH. TaniguchiH. ShimadaM. DotsuY. UmeyamaY. TomonoH. KitazakiT. FukudaM. SodaH. YamaguchiH. FukudaM. MukaeH. Amrubicin in previously treated patients with malignant pleural mesothelioma: A phase II study.Thorac. Cancer202011719721978https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7327919/10.1111/1759‑7714.1349032462731
    [Google Scholar]
  62. WangZ. WangM. LiuJ. YeJ. JiangH. XuY. YeD. WanJ. Inhibition of TRPA1 attenuates doxorubicin‐induced acute cardiotoxicity by suppressing oxidative stress, the inflammatory response, and endoplasmic reticulum stress.Oxid. Med. Cell. Longev.201820181517946810.1155/2018/517946829682158
    [Google Scholar]
  63. LiangX. WangS. WangL. CeylanA.F. RenJ. ZhangY. Mitophagy inhibitor liensinine suppresses doxorubicin-induced cardiotoxicity through inhibition of Drp1-mediated maladaptive mitochondrial fission.Pharmacol. Res.202015710484610.1016/j.phrs.2020.10484632339784
    [Google Scholar]
  64. LlachA. MazevetM. MateoP. VillejouvertO. RidouxA. Rucker-MartinC. RibeiroM. FischmeisterR. CrozatierB. BenitahJ.P. MorelE. GómezA.M. Progression of excitation-contraction coupling defects in doxorubicin cardiotoxicity.J. Mol. Cell. Cardiol.201912612913910.1016/j.yjmcc.2018.11.01930500377
    [Google Scholar]
  65. WangX. LiC. WangQ. LiW. GuoD. ZhangX. ShaoM. ChenX. MaL. ZhangQ. WangW. WangY. Tanshinone IIA restores dynamic balance of autophagosome/autolysosome in doxorubicin-induced cardiotoxicity via targeting Beclin1/LAMP1.Cancers201911791010.3390/cancers1107091031261758
    [Google Scholar]
  66. WangM. SunG. SunX. WangH. MengX. QinM. SunJ. LuoY. SunX. Cardioprotective effect of salvianolic acid B against arsenic trioxide-induced injury in cardiac H9c2 cells via the PI3K/Akt signal pathway.Toxicol. Lett.20132162-310010710.1016/j.toxlet.2012.11.02323201927
    [Google Scholar]
  67. AikawaR. NawanoM. GuY. KatagiriH. AsanoT. ZhuW. NagaiR. KomuroI. Insulin prevents cardiomyocytes from oxidative stress-induced apoptosis through activation of PI3 kinase/Akt.Circulation2000102232873287910.1161/01.CIR.102.23.287311104747
    [Google Scholar]
  68. SiR. TaoL. ZhangH.F. YuQ.J. ZhangR. LvA.L. ZhouN. CaoF. GuoW.Y. RenJ. WangH.C. GaoF. Survivin: A novel player in insulin cardioprotection against myocardial ischemia/reperfusion injury.J. Mol. Cell. Cardiol.2011501162410.1016/j.yjmcc.2010.08.01720801129
    [Google Scholar]
  69. ChenM. ZhangH. WuJ. XuL. XuD. SunJ. HeY. ZhouX. WangZ. WuL. XuS. WangJ. JiangS. ZhouX. HoffmanA.R. HuX. HuJ. LiT. Promotion of the induction of cell pluripotency through metabolic remodeling by thyroid hormone triiodothyronine-activated PI3K/Akt signal pathway.Biomaterials201233225514552310.1016/j.biomaterials.2012.04.00122575839
    [Google Scholar]
  70. MohanM. MannanA. SinghT.G. Therapeutic implication of Sonic Hedgehog as a potential modulator in ischemic injury.Pharmacol. Rep.202375483886010.1007/s43440‑023‑00505‑037347388
    [Google Scholar]
  71. BurgeringB.M.T. CofferP.J. Protein kinase B (c-Akt) in phosphatidylinositol-3-OH kinase signal transduction.Nature1995376654159960210.1038/376599a07637810
    [Google Scholar]
  72. FayardE. TintignacL.A. BaudryA. HemmingsB.A. Protein kinase B/Akt at a glance.J. Cell Sci.2005118245675567810.1242/jcs.0272416339964
    [Google Scholar]
  73. TestaJ.R. TsichlisP.N. Akt signaling in normal and malignant cells.Oncogene200524507391739310.1038/sj.onc.120910016288285
    [Google Scholar]
  74. VaraJ.Á.F. CasadoE. de CastroJ. CejasP. Belda-IniestaC. González-BarónM. PI3K/Akt signalling pathway and cancer.Cancer Treat. Rev.200430219320410.1016/j.ctrv.2003.07.00715023437
    [Google Scholar]
  75. AoyagiT. MatsuiT. Phosphoinositide-3 kinase signaling in cardiac hypertrophy and heart failure.Curr. Pharm. Des.201117181818182410.2174/13816121179639097621631421
    [Google Scholar]
  76. LiaoZ.Q. JiangY.N. SuZ.L. BiH.L. LiJ.T. LiC.L. YangX.L. ZhangY. XieX. Rutaecarpine inhibits doxorubicin-induced oxidative stress and apoptosis by activating AKT signaling pathway.Front. Cardiovasc. Med.2022880968910.3389/fcvm.2021.80968935071368
    [Google Scholar]
  77. McLeanB.A. PatelV.B. ZhabyeyevP. ChenX. BasuR. WangF. ShahS. VanhaesebroeckB. OuditG.Y. PI3Kα pathway inhibition with doxorubicin treatment results in distinct biventricular atrophy and remodeling with right ventricular dysfunction.J. Am. Heart Assoc.201989e01096110.1161/JAHA.118.01096131039672
    [Google Scholar]
  78. TaniyamaY. WalshK. Elevated myocardial Akt signaling ameliorates doxorubicin-induced congestive heart failure and promotes heart growth.J. Mol. Cell. Cardiol.200234101241124710.1006/jmcc.2002.206812392981
    [Google Scholar]
  79. YaoH. HanX. HanX. The cardioprotection of the insulin-mediated PI3K/Akt/mTOR signaling pathway.Am. J. Cardiovasc. Drugs201414643344210.1007/s40256‑014‑0089‑925160498
    [Google Scholar]
  80. SaxtonR.A. SabatiniD.M. mTOR signaling in growth, metabolism, and disease.Cell2017168696097610.1016/j.cell.2017.02.00428283069
    [Google Scholar]
  81. SinghS. SinghT.G. RehniA.K. An insight into molecular mechanisms and novel therapeutic approaches in epileptogenesis.CNS Neurol. Disord. Drug Targets2021191075077910.2174/187152731966620091015382732914725
    [Google Scholar]
  82. DowlingR.J.O. TopisirovicI. FonsecaB.D. SonenbergN. Dissecting the role of mTOR: Lessons from mTOR inhibitors.Biochim. Biophys. Acta. Proteins Proteomics20101804343343910.1016/j.bbapap.2009.12.00120005306
    [Google Scholar]
  83. XiaoB. HongL. CaiX. MeiS. ZhangP. ShaoL. The true colors of autophagy in doxorubicin‑induced cardiotoxicity (Review).Oncol. Lett.20191832165217210.3892/ol.2019.1057631452719
    [Google Scholar]
  84. ZouZ. TaoT. LiH. ZhuX. mTOR signaling pathway and mTOR inhibitors in cancer: Progress and challenges.Cell Biosci.20201013110.1186/s13578‑020‑00396‑132175074
    [Google Scholar]
  85. SciarrettaS. ForteM. FratiG. SadoshimaJ. New insights into the role of mTOR signaling in the cardiovascular system.Circ. Res.2018122348950510.1161/CIRCRESAHA.117.31114729420210
    [Google Scholar]
  86. ZhuY. PiresK.M.P. WhiteheadK.J. OlsenC.D. WaymentB. ZhangY.C. BuggerH. IlkunO. LitwinS.E. ThomasG. KozmaS.C. AbelE.D. Mechanistic target of rapamycin (mTOR) is essential for murine embryonic heart development and growth.PLoS One201381e5422110.1371/journal.pone.005422123342106
    [Google Scholar]
  87. GaoG. ChenW. YanM. LiuJ. LuoH. WangC. YangP. Rapamycin regulates the balance between cardiomyocyte apoptosis and autophagy in chronic heart failure by inhibiting mTOR signaling.Int. J. Mol. Med.202045119520931746373
    [Google Scholar]
  88. ChenM.B. WuX.Y. GuJ.H. GuoQ.T. ShenW.X. LuP.H. Activation of AMP-activated protein kinase contributes to doxorubicin-induced cell death and apoptosis in cultured myocardial H9c2 cells.Cell Biochem. Biophys.201160331132210.1007/s12013‑011‑9153‑021274754
    [Google Scholar]
  89. ChongZ.Z. ShangY.C. MaieseK. Cardiovascular disease and mTOR signaling.Trends Cardiovasc. Med.201121515115510.1016/j.tcm.2012.04.00522732551
    [Google Scholar]
  90. PizarroM. TroncosoR. MartínezG.J. ChiongM. CastroP.F. LavanderoS. Basal autophagy protects cardiomyocytes from doxorubicin-induced toxicity.Toxicology2016370414810.1016/j.tox.2016.09.01127666003
    [Google Scholar]
  91. XuZ.M. LiC.B. LiuQ.L. LiP. YangH. Ginsenoside Rg1 prevents doxorubicin-induced cardiotoxicity through the inhibition of autophagy and endoplasmic reticulum stress in mice.Int. J. Mol. Sci.20181911365810.3390/ijms1911365830463294
    [Google Scholar]
  92. AoyamaT. MatsuiT. NovikovM. ParkJ. HemmingsB. RosenzweigA. Serum and glucocorticoid-responsive kinase-1 regulates cardiomyocyte survival and hypertrophic response.Circulation2005111131652165910.1161/01.CIR.0000160352.58142.0615795328
    [Google Scholar]
  93. ShendeP. XuL. MorandiC. PentassugliaL. HeimP. LebboukhS. BerthonnecheC. PedrazziniT. KaufmannB.A. HallM.N. RüeggM.A. BrinkM. Cardiac mTOR complex 2 preserves ventricular function in pressure-overload hypertrophy.Cardiovasc. Res.2016109110311410.1093/cvr/cvv25226598511
    [Google Scholar]
  94. WuY. WangJ. YuX. LiD. HanX. FanL. Sevoflurane ameliorates doxorubicin-induced myocardial injury by affecting the phosphorylation states of proteins in PI3K/Akt/mTOR signaling pathway.Cardiol. J.201724440941810.5603/CJ.a2017.001828198521
    [Google Scholar]
  95. ChristidiE. BrunhamL.R. Regulated cell death pathways in doxorubicin-induced cardiotoxicity.Cell Death Dis.202112433910.1038/s41419‑021‑03614‑x33795647
    [Google Scholar]
  96. WangX. WangQ. LiW. ZhangQ. JiangY. GuoD. SunX. LuW. LiC. WangY. TFEB-NF-κB inflammatory signaling axis: A novel therapeutic pathway of Dihydrotanshinone I in doxorubicin-induced cardiotoxicity.J. Exp. Clin. Cancer Res.20203919310.1186/s13046‑020‑01595‑x32448281
    [Google Scholar]
  97. DeviS. ChauhanS. MannanA. SinghT.G. Targeting cardiovascular risk factors with eugenol: An anti-inflammatory perspective.Inflammopharmacology20243213071738085446
    [Google Scholar]
  98. QuagliarielloV De LaurentiisM ReaD BarbieriA MontiMG BottiG MaureaN SGLT2 inhibitor dapagliflozin against anthracycline and trastuzumab-induced cardiotoxicity: The role of MYD88, NLRP3, Leukotrienes/Interleukin 6 axis and mTORC1/Fox01/3a mediated apoptosis.Eur. Heart J.202041Supplement_2ehaa946.3253ehaa946.3253
    [Google Scholar]
  99. EganD. KimJ. ShawR.J. GuanK.L. The autophagy initiating kinase ULK1 is regulated via opposing phosphorylation by AMPK and mTOR.Autophagy20117664364410.4161/auto.7.6.1512321460621
    [Google Scholar]
  100. HongE.G. KimB.W. Young JungD. Hun KimJ. YuT. Seixas Da SilvaW. FriedlineR.H. BiancoS.D. SeslarS.P. WakimotoH. BerulC.I. RussellK.S. Won LeeK. LarsenP.R. BiancoA.C. KimJ.K. Cardiac expression of human type 2 iodothyronine deiodinase increases glucose metabolism and protects against doxorubicin-induced cardiac dysfunction in male mice.Endocrinology2013154103937394610.1210/en.2012‑226123861374
    [Google Scholar]
  101. NazarkoV.Y. ZhongQ. ULK1 targets Beclin-1 in autophagy.Nat. Cell Biol.201315772772810.1038/ncb279723817237
    [Google Scholar]
  102. HarrisM.P. ZhangQ.J. CochranC.T. PonceJ. AlexanderS. KronembergerA. FuquaJ.D. ZhangY. FattalR. HarperT. MurryM.L. GrueterC.E. AbelE.D. LiraV.A. Perinatal versus adult loss of ULK1 and ULK2 distinctly influences cardiac autophagy and function.Autophagy20221892161217710.1080/15548627.2021.202228935104184
    [Google Scholar]
  103. SangweniN.F. GabuzaK. HuisamenB. MabasaL. van VuurenD. JohnsonR. Molecular insights into the pathophysiology of doxorubicin-induced cardiotoxicity: A graphical representation.Arch. Toxicol.20229661541155010.1007/s00204‑022‑03262‑w35333943
    [Google Scholar]
  104. RussoM. BonoE. GhigoA. The interplay between autophagy and senescence in anthracycline cardiotoxicity.Curr. Heart Fail. Rep.202118418019010.1007/s11897‑021‑00519‑w34081265
    [Google Scholar]
  105. XuX. ChenK. KobayashiS. TimmD. LiangQ. Resveratrol attenuates doxorubicin-induced cardiomyocyte death via inhibition of p70 S6 kinase 1-mediated autophagy.J. Pharmacol. Exp. Ther.2012341118319510.1124/jpet.111.18958922209892
    [Google Scholar]
  106. YuX. YangY. ChenT. WangY. GuoT. LiuY. LiH. YangL. Cell death regulation in myocardial toxicity induced by antineoplastic drugs.Front. Cell Dev. Biol.202311107591710.3389/fcell.2023.107591736824370
    [Google Scholar]
  107. LiD.L. WangZ.V. DingG. TanW. LuoX. CriolloA. XieM. JiangN. MayH. KyrychenkoV. SchneiderJ.W. GilletteT.G. HillJ.A. Doxorubicin blocks cardiomyocyte autophagic flux by inhibiting lysosome acidification.Circulation2016133171668168710.1161/CIRCULATIONAHA.115.01744326984939
    [Google Scholar]
  108. LiM. RussoM. PirozziF. TocchettiC.G. GhigoA. Autophagy and cancer therapy cardiotoxicity: From molecular mechanisms to therapeutic opportunities.Biochim. Biophys. Acta Mol. Cell Res.20201867311849310.1016/j.bbamcr.2019.06.00731233802
    [Google Scholar]
  109. BartlettJ.J. TrivediP.C. YeungP. KienesbergerP.C. PulinilkunnilT. Doxorubicin impairs cardiomyocyte viability by suppressing transcription factor EB expression and disrupting autophagy.Biochem. J.2016473213769378910.1042/BCJ2016038527487838
    [Google Scholar]
  110. ChenC. JiangL. ZhangM. PanX. PengC. HuangW. JiangQ. Isodunnianol alleviates doxorubicin-induced myocardial injury by activating protective autophagy.Food Funct.20191052651265710.1039/C9FO00063A31025676
    [Google Scholar]
  111. FarhanM. WangH. GaurU. LittleP.J. XuJ. ZhengW. FoxO signaling pathways as therapeutic targets in cancer.Int. J. Biol. Sci.201713781582710.7150/ijbs.2005228808415
    [Google Scholar]
  112. ZhangY. GanB. LiuD. PaikJ. FoxO family members in cancer.Cancer Biol. Ther.201112425325910.4161/cbt.12.4.1595421613825
    [Google Scholar]
  113. MishraS. RaviV. SundaresanN.R. Role of FoxO transcription factors in aging-associated cardiovascular diseases.Vitam. Horm.202111544947510.1016/bs.vh.2020.12.01833706958
    [Google Scholar]
  114. HornsveldM. DansenT.B. DerksenP.W. BurgeringB.M.T. Re-evaluating the role of FOXOs in cancer.Semin. Cancer Biol.2018509010010.1016/j.semcancer.2017.11.01729175105
    [Google Scholar]
  115. XinZ. MaZ. JiangS. WangD. FanC. DiS. HuW. LiT. SheJ. YangY. FOXOs in the impaired heart: New therapeutic targets for cardiac diseases.Biochim. Biophys. Acta Mol. Basis Dis.20171863248649810.1016/j.bbadis.2016.11.02327890702
    [Google Scholar]
  116. SeokH.Y. ChenJ. KataokaM. HuangZ.P. DingJ. YanJ. HuX. WangD.Z. Loss of MicroRNA-155 protects the heart from pathological cardiac hypertrophy.Circ. Res.2014114101585159510.1161/CIRCRESAHA.114.30378424657879
    [Google Scholar]
  117. UcarA. GuptaS.K. FiedlerJ. ErikciE. KardasinskiM. BatkaiS. DangwalS. KumarswamyR. BangC. HolzmannA. RemkeJ. CaprioM. JentzschC. EngelhardtS. GeisendorfS. GlasC. HofmannT.G. NesslingM. RichterK. SchifferM. CarrierL. NappL.C. BauersachsJ. ChowdhuryK. ThumT. The miRNA-212/132 family regulates both cardiac hypertrophy and cardiomyocyte autophagy.Nat. Commun.201231107810.1038/ncomms209023011132
    [Google Scholar]
  118. SunZ. YanB. YuW.Y. YaoX. MaX. ShengG. MaQ. Vitexin attenuates acute doxorubicin cardiotoxicity in rats via the suppression of oxidative stress, inflammation and apoptosis and the activation of FOXO3a.Exp. Ther. Med.20161231879188410.3892/etm.2016.351827588105
    [Google Scholar]
  119. XiaP. ChenJ. LiuY. FletcherM. JensenB.C. ChengZ. Doxorubicin induces cardiomyocyte apoptosis and atrophy through cyclin-dependent kinase 2–mediated activation of forkhead box O1.J. Biol. Chem.2020295134265427610.1074/jbc.RA119.01157132075913
    [Google Scholar]
  120. HuiR.C.Y. FrancisR.E. GuestS.K. CostaJ.R. GomesA.R. MyattS.S. BrosensJ.J. LamE.W.F. Doxorubicin activates FOXO3a to induce the expression of multidrug resistance gene ABCB1 ( MDR1 ) in K562 leukemic cells.Mol. Cancer Ther.20087367067810.1158/1535‑7163.MCT‑07‑039718347152
    [Google Scholar]
  121. HuiR.C.Y. GomesA.R. ConstantinidouD. CostaJ.R. KaradedouC.T. Fernandez de MattosS. WymannM.P. BrosensJ.J. SchulzeA. LamE.W.F. The forkhead transcription factor FOXO3a increases phosphoinositide-3 kinase/Akt activity in drug-resistant leukemic cells through induction of PIK3CA expression.Mol. Cell. Biol.200828195886589810.1128/MCB.01265‑0718644865
    [Google Scholar]
  122. HoK.K. McGuireV.A. KooC.Y. MuirK.W. de OlanoN. MaifoshieE. KellyD.J. McGovernU.B. MonteiroL.J. GomesA.R. NebredaA.R. CampbellD.G. ArthurJ.S.C. LamE.W.F. Phosphorylation of FOXO3a on Ser-7 by p38 promotes its nuclear localization in response to doxorubicin.J. Biol. Chem.201228721545155510.1074/jbc.M111.28422422128155
    [Google Scholar]
  123. ZhouL. LiR. LiuC. SunT. Htet AungL.H. ChenC. GaoJ. ZhaoY. WangK. Foxo3a inhibits mitochondrial fission and protects against doxorubicin-induced cardiotoxicity by suppressing MIEF2.Free Radic. Biol. Med.201710436037010.1016/j.freeradbiomed.2017.01.03728137654
    [Google Scholar]
  124. LiuM.H. ZhangY. HeJ. TanT.P. WuS.J. GuoD.M. HeH. PengJ. TangZ.H. JiangZ.S. Hydrogen sulfide protects H9c2 cardiac cells against doxorubicin-induced cytotoxicity through the PI3K/Akt/FoxO3a pathway.Int. J. Mol. Med.20163761661166810.3892/ijmm.2016.256327081862
    [Google Scholar]
  125. ZhangC. FengY. QuS. WeiX. ZhuH. LuoQ. LiuM. ChenG. XiaoX. Resveratrol attenuates doxorubicin-induced cardiomyocyte apoptosis in mice through SIRT1-mediated deacetylation of p53.Cardiovasc. Res.201190353854510.1093/cvr/cvr02221278141
    [Google Scholar]
  126. TaoR. ColemanM.C. PenningtonJ.D. OzdenO. ParkS.H. JiangH. KimH.S. FlynnC.R. HillS. Hayes McDonaldW. OlivierA.K. SpitzD.R. GiusD. Sirt3-mediated deacetylation of evolutionarily conserved lysine 122 regulates MnSOD activity in response to stress.Mol. Cell201040689390410.1016/j.molcel.2010.12.01321172655
    [Google Scholar]
  127. ZhengY. ShiB. MaM. WuX. LinX. The novel relationship between Sirt3 and autophagy in myocardial ischemia–reperfusion.J. Cell. Physiol.201923455488549510.1002/jcp.2732930485429
    [Google Scholar]
  128. LiH. ZhangM. WangY. GongK. YanT. WangD. MengX. YangX. ChenY. HanJ. DuanY. ZhangS. Daidzein alleviates doxorubicin-induced heart failure via the SIRT3/FOXO3a signaling pathway.Food Funct.202213189576958810.1039/D2FO00772J36000402
    [Google Scholar]
  129. LochheadP.A. KinstrieR. SibbetG. RawjeeT. MorriceN. CleghonV. A chaperone-dependent GSK3beta transitional intermediate mediates activation-loop autophosphorylation.Mol. Cell200624462763310.1016/j.molcel.2006.10.00917188038
    [Google Scholar]
  130. SharmaV. KaurA. SinghT.G. Counteracting role of nuclear factor erythroid 2-related factor 2 pathway in Alzheimer’s disease.Biomed. Pharmacother.202012911037310.1016/j.biopha.2020.11037332603894
    [Google Scholar]
  131. GoyalS. SinghM. ThirumalD. SharmaP. MujwarS. MishraK.K. SinghT.G. SinghR. SinghV. SinghT. AhmadS.F. In silico approaches to developing novel glycogen synthase kinase 3β (GSK-3β) inhibitors.Biomedicines20231110278410.3390/biomedicines1110278437893156
    [Google Scholar]
  132. SutherlandC. CohenP. The α‐isoform of glycogen synthase kinase‐3 from rabbit skeletal muscle is inactivated by p70 S6 kinase or MAP kinase‐activated protein kinase‐1 in vitro.FEBS Lett.19943381374210.1016/0014‑5793(94)80112‑68307153
    [Google Scholar]
  133. DieL. YanP. Jun JiangZ. Min HuaT. CaiW. XingL. Glycogen synthase kinase-3 beta inhibitor suppresses Porphyromonas gingivalis lipopolysaccharide-induced CD40 expression by inhibiting nuclear factor-kappa B activation in mouse osteoblasts.Mol. Immunol.2012521384910.1016/j.molimm.2012.04.00522580404
    [Google Scholar]
  134. ZhouJ. AhmadF. ParikhS. HoffmanN.E. RajanS. VermaV.K. SongJ. YuanA. ShanmughapriyaS. GuoY. GaoE. KochW. WoodgettJ.R. MadeshM. KishoreR. LalH. ForceT. Loss of adult cardiac myocyte GSK-3 leads to mitotic catastrophe resulting in fatal dilated cardiomyopathy.Circ. Res.201611881208122210.1161/CIRCRESAHA.116.30854426976650
    [Google Scholar]
  135. MatsudaT. ZhaiP. MaejimaY. HongC. GaoS. TianB. GotoK. TakagiH. Tamamori-AdachiM. KitajimaS. SadoshimaJ. Distinct roles of GSK-3α and GSK-3β phosphorylation in the heart under pressure overload.Proc. Natl. Acad. Sci. USA200810552209002090510.1073/pnas.080831510619106302
    [Google Scholar]
  136. ChengH. WoodgettJ. MaamariM. ForceT. Targeting GSK-3 family members in the heart: A very sharp double-edged sword.J. Mol. Cell. Cardiol.201151460761310.1016/j.yjmcc.2010.11.02021163265
    [Google Scholar]
  137. Nagoor MeeranM.F. ArunachalamS. AzimullahS. SaraswathiammaD. AlbawardiA. AlmarzooqiS. JhaN.K. SubramanyaS. BeiramR. OjhaS. α-Bisabolol, a dietary sesquiterpene, attenuates doxorubicin-induced acute cardiotoxicity in rats by inhibiting cellular signaling pathways, Nrf2/Keap-1/HO-1, Akt/mTOR/GSK-3β, NF-κB/p38/MAPK, and NLRP3 inflammasomes regulating oxidative stress and inflammatory cascades.Int. J. Mol. Sci.202324181401310.3390/ijms24181401337762315
    [Google Scholar]
  138. WangF. ShuF. WangX.Q. ZhengL.L. WangH.L. LiL. LvH.G. Sevoflurane ameliorates adriamycin-induced myocardial injury in rats through the PI3K/Akt/GSK-3β pathway.Eur. Rev. Med. Pharmacol. Sci.202125296897533577052
    [Google Scholar]
  139. LiaoW. RaoZ. WuL. ChenY. LiC. Cariporide attenuates doxorubicin-induced cardiotoxicity in rats by inhibiting oxidative stress, inflammation, and apoptosis partly through regulation of Akt/GSK-3β and Sirt1 signaling pathways.Front. Pharmacol.20221385005310.3389/fphar.2022.85005335747748
    [Google Scholar]
  140. AhmadF. SinghA.P. TomarD. RahmaniM. ZhangQ. WoodgettJ.R. TilleyD.G. LalH. ForceT. Cardiomyocyte-GSK-3α promotes mPTP opening and heart failure in mice with chronic pressure overload.J. Mol. Cell. Cardiol.2019130657510.1016/j.yjmcc.2019.03.02030928428
    [Google Scholar]
  141. JuhaszovaM. ZorovD.B. KimS.H. PepeS. FuQ. FishbeinK.W. ZimanB.D. WangS. YtrehusK. AntosC.L. OlsonE.N. SollottS.J. Glycogen synthase kinase-3β mediates convergence of protection signaling to inhibit the mitochondrial permeability transition pore.J. Clin. Invest.2004113111535154910.1172/JCI1990615173880
    [Google Scholar]
  142. WangX. SunQ. JiangQ. JiangY. ZhangY. CaoJ. LuL. LiC. WeiP. WangQ. WangY. Cryptotanshinone ameliorates doxorubicin-induced cardiotoxicity by targeting Akt-GSK-3β-mPTP pathway in vitro.Molecules2021265146010.3390/molecules2605146033800264
    [Google Scholar]
  143. HeS.F. JinS.Y. WuH. WangB. WuY.X. ZhangS.J. IrwinM.G. WongT.M. ZhangY. Morphine preconditioning confers cardioprotection in doxorubicin-induced failing rat hearts via ERK/GSK-3β pathway independent of PI3K/Akt.Toxicol. Appl. Pharmacol.2015288334935810.1016/j.taap.2015.08.00726296503
    [Google Scholar]
  144. WangS. SunM. DingS. LiuC. WangJ. HanS. LinX. LiQ. Ticagrelor reduces doxorubicin-induced pyroptosis of rat cardiomyocytes by targeting GSK-3β/caspase-1.Front. Cardiovasc. Med.20239109060110.3389/fcvm.2022.109060136684601
    [Google Scholar]
  145. WuJ. SunC. WangR. LiJ. ZhouM. YanM. XueX. WangC. Cardioprotective effect of paeonol against epirubicin-induced heart injury via regulating miR-1 and PI3K/AKT pathway.Chem. Biol. Interact.2018286172510.1016/j.cbi.2018.02.03529505745
    [Google Scholar]
  146. ZhanL. WangX. ZhangY. ZhuG. DingY. ChenX. JiangW. WuS. Benazepril hydrochloride protects against doxorubicin cardiotoxicity by regulating the PI3K/Akt pathway.Exp. Ther. Med.2021224108210.3892/etm.2021.1051634447475
    [Google Scholar]
  147. ZhangX. WangX. LiuX. LuoW. ZhaoH. YinY. XuK. Myocardial protection of propofol on apoptosis induced by anthracycline by PI3K/AKT/Bcl-2 pathway in rats.Ann. Transl. Med.2022101055510.21037/atm‑22‑154935722399
    [Google Scholar]
  148. Kalantary-CharvadehA. SanajouD. Hemmati-DinarvandM. MarandiY. KhojastehfardM. HajipourH. Mesgari-AbbasiM. RoshangarL. Nazari Soltan AhmadS. Micheliolide protects against doxorubicin-induced cardiotoxicity in mice by regulating PI3K/Akt/NF-kB signaling pathway.Cardiovasc. Toxicol.201919429730510.1007/s12012‑019‑09511‑230835049
    [Google Scholar]
  149. CaoY. RuanY. ShenT. HuangX. LiM. YuW. ZhuY. ManY. WangS. LiJ. Astragalus polysaccharide suppresses doxorubicin-induced cardiotoxicity by regulating the PI3k/Akt and p38MAPK pathways.Oxid. Med. Cell. Longev.2014201411210.1155/2014/67421925386226
    [Google Scholar]
  150. YuW. SunH. ZhaW. CuiW. XuL. MinQ. WuJ. Apigenin attenuates adriamycin-induced cardiomyocyte apoptosis via the PI3K/AKT/mTOR pathway.Evid. Based Complement. Alternat. Med.201720171259067610.1155/2017/259067628684964
    [Google Scholar]
  151. WangF. WangL. JiaoY. WangZ. Qishen Huanwu capsule reduces pirarubicin-induced cardiotoxicity in rats by activating the PI3K/Akt/mTOR pathway.Ann. Palliat. Med.2020953453346110.21037/apm‑20‑174633065796
    [Google Scholar]
  152. SahuR. DuaT.K. DasS. De FeoV. DewanjeeS. Wheat phenolics suppress doxorubicin-induced cardiotoxicity via inhibition of oxidative stress, MAP kinase activation, NF-κB pathway, PI3K/Akt/mTOR impairment, and cardiac apoptosis.Food Chem. Toxicol.201912550351910.1016/j.fct.2019.01.03430735749
    [Google Scholar]
  153. ChenY.L. ZhuangX.D. XuZ.W. LuL.H. GuoH.L. WuW.K. LiaoX.X. Higenamine combined with [6]-gingerol suppresses doxorubicin-triggered oxidative stress and apoptosis in cardiomyocytes via upregulation of PI3K/Akt pathway.Evid. Based Complement. Alternat. Med.2013201311410.1155/2013/97049023861719
    [Google Scholar]
  154. HsiehP.L. ChuP.M. ChengH.C. HuangY.T. ChouW.C. TsaiK.L. ChanS.H. Dapagliflozin mitigates doxorubicin-caused myocardium damage by regulating AKT-mediated oxidative stress, cardiac remodeling, and inflammation.Int. J. Mol. Sci.202223171014610.3390/ijms23171014636077544
    [Google Scholar]
  155. LuY. MinQ. ZhaoX. LiL. ZhaoG. DongJ. Eupatilin attenuates doxorubicin-induced cardiotoxicity by activating the PI3K-AKT signaling pathway in mice.Mol. Cell. Biochem.202447948698037222879
    [Google Scholar]
  156. LiH. MaoY. ZhangQ. HanQ. ManZ. ZhangJ. WangX. HuR. ZhangX. IrwinD.M. NiuG. TanH. Xinmailong mitigated epirubicin-induced cardiotoxicity via inhibiting autophagy.J. Ethnopharmacol.201619245947010.1016/j.jep.2016.08.03127586823
    [Google Scholar]
  157. AlzahraniA.M. RajendranP. VeeraraghavanV.P. HaniehH. Cardiac protective effect of kirenol against doxorubicin-induced cardiac hypertrophy in H9c2 cells through Nrf2 signaling via PI3K/AKT pathways.Int. J. Mol. Sci.2021226326910.3390/ijms2206326933806909
    [Google Scholar]
  158. AbbasN.A.T. KabilS.L. Liraglutide ameliorates cardiotoxicity induced by doxorubicin in rats through the Akt/GSK-3β signaling pathway.Naunyn Schmiedebergs Arch. Pharmacol.2017390111145115310.1007/s00210‑017‑1414‑z28780599
    [Google Scholar]
  159. HuX. LiB. LiL. LiB. LuoJ. ShenB. Asiatic acid protects against doxorubicin-induced cardiotoxicity in mice.Oxid. Med. Cell. Longev.2020202011210.1155/2020/534720432509145
    [Google Scholar]
  160. HeY. YangZ. LiJ. LiE. Dexmedetomidine reduces the inflammation and apoptosis of doxorubicin-induced myocardial cells.Exp. Mol. Pathol.202011310437110.1016/j.yexmp.2020.10437131917290
    [Google Scholar]
  161. Soares-SilvaM. DinizF.F. GomesG.N. BahiaD. The mitogen-activated protein kinase (MAPK) pathway: Role in immune evasion by trypanosomatids.Front. Microbiol.2016718310.3389/fmicb.2016.0018326941717
    [Google Scholar]
  162. SinghS. SinghT.G. Emerging perspectives on mitochondrial dysfunctioning and inflammation in epileptogenesis.Inflamm. Res.20217010-121027104210.1007/s00011‑021‑01511‑934652489
    [Google Scholar]
  163. SharmaV. SinghT.G. mannanA. Therapeutic implications of glucose transporters (GLUT) in cerebral ischemia.Neurochem. Res.20224782173218610.1007/s11064‑022‑03620‑135596882
    [Google Scholar]
  164. WangY. Mitogen-activated protein kinases in heart development and diseases.Circulation2007116121413142310.1161/CIRCULATIONAHA.106.67958917875982
    [Google Scholar]
  165. DavisR.J. The mitogen-activated protein kinase signal transduction pathway.J. Biol. Chem.199326820145531455610.1016/S0021‑9258(18)82362‑68325833
    [Google Scholar]
  166. SatohT. NakafukuM. KaziroY. Function of Ras as a molecular switch in signal transduction.J. Biol. Chem.199226734241492415210.1016/S0021‑9258(18)35739‑91447166
    [Google Scholar]
  167. Rozakis-AdcockM. McGladeJ. MbamaluG. PelicciG. DalyR. LiW. BatzerA. ThomasS. BruggeJ. PelicciP.G. SchlessingerJ. PawsonT. Association of the Shc and Grb2/Sem5 SH2-containing proteins is implicated in activation of the Ras pathway by tyrosine kinases.Nature1992360640568969210.1038/360689a01465135
    [Google Scholar]
  168. YamazakiT. KomuroI. ZouY. KudohS. ShiojimaI. HiroiY. MizunoT. AikawaR. TakanoH. YazakiY. Norepinephrine induces the raf-1 kinase/mitogen-activated protein kinase cascade through both alpha 1- and beta-adrenoceptors.Circulation19979551260126810.1161/01.CIR.95.5.12609054858
    [Google Scholar]
  169. ZhuW. ZouY. AikawaR. HaradaK. KudohS. UozumiH. HayashiD. GuY. YamazakiT. NagaiR. YazakiY. KomuroI. MAPK superfamily plays an important role in daunomycin-induced apoptosis of cardiac myocytes.Circulation1999100202100210710.1161/01.CIR.100.20.210010562267
    [Google Scholar]
  170. LiuJ. MaoW. DingB. LiangC. ERKs/p53 signal transduction pathway is involved in doxorubicin-induced apoptosis in H9c2 cells and cardiomyocytes.Am. J. Physiol. Heart Circ. Physiol.20082955H1956H196510.1152/ajpheart.00407.200818775851
    [Google Scholar]
  171. GuoR.M. XuW.M. LinJ.C. MoL.Q. HuaX.X. ChenP.X. WuK. ZhengD.D. FengJ.Q. Activation of the p38 MAPK/NF-κB pathway contributes to doxorubicin-induced inflammation and cytotoxicity in H9c2 cardiac cells.Mol. Med. Rep.20138260360810.3892/mmr.2013.155423807148
    [Google Scholar]
  172. TorresJ. Enríquez-de-SalamancaA. FernándezI. Rodríguez-AresM.T. QuadradoM.J. MurtaJ. Benítez del CastilloJ.M. SternM.E. CalongeM. Activation of MAPK signaling pathway and NF-kappaB activation in pterygium and ipsilateral pterygium-free conjunctival specimens.Invest. Ophthalmol. Vis. Sci.20115285842585210.1167/iovs.10‑667321685342
    [Google Scholar]
  173. DongC. DavisR.J. FlavellR.A. MAP kinases in the immune response.Annu. Rev. Immunol.2002201557210.1146/annurev.immunol.20.091301.13113311861597
    [Google Scholar]
  174. ArthurJ.S.C. LeyS.C. Mitogen-activated protein kinases in innate immunity.Nat. Rev. Immunol.201313967969210.1038/nri349523954936
    [Google Scholar]
  175. El-AgamyD.S. El-HarbiK.M. KhoshhalS. AhmedN. ElkablawyM.A. ShaabanA.A. Abo-HadedH.M. Pristimerin protects against doxorubicin-induced cardiotoxicity and fibrosis through modulation of Nrf2 and MAPK/NF-kB signaling pathways.Cancer Manag. Res.201811476110.2147/CMAR.S18669630588110
    [Google Scholar]
  176. WenS.Y. TsaiC.Y. PaiP.Y. ChenY.W. YangY.C. AnejaR. HuangC.Y. KuoW.W. Diallyl trisulfide suppresses doxorubicin‐induced cardiomyocyte apoptosis by inhibiting MAPK/NF‐κB signaling through attenuation of ROS generation.Environ. Toxicol.20183319310310.1002/tox.2250029087013
    [Google Scholar]
  177. MenegonS. ColumbanoA. GiordanoS. The dual roles of NRF2 in cancer.Trends Mol. Med.201622757859310.1016/j.molmed.2016.05.00227263465
    [Google Scholar]
  178. FãoL. MotaS.I. RegoA.C. Shaping the Nrf2-ARE-related pathways in Alzheimer’s and Parkinson’s diseases.Ageing Res. Rev.20195410094210.1016/j.arr.2019.10094231415806
    [Google Scholar]
  179. YamamotoM. KenslerT.W. MotohashiH. The KEAP1-NRF2 system: A thiol-based sensor-effector apparatus for maintaining redox homeostasis.Physiol. Rev.20189831169120310.1152/physrev.00023.201729717933
    [Google Scholar]
  180. KeumY.S. ChoiB. Molecular and chemical regulation of the Keap1-Nrf2 signaling pathway.Molecules2014197100741008910.3390/molecules19071007425014534
    [Google Scholar]
  181. NordgrenK.K.S. WallaceK.B. Keap1 redox-dependent regulation of doxorubicin-induced oxidative stress response in cardiac myoblasts.Toxicol. Appl. Pharmacol.2014274110711610.1016/j.taap.2013.10.02324211725
    [Google Scholar]
  182. LuoL.F. GuanP. QinL.Y. WangJ.X. WangN. JiE.S. Astragaloside IV inhibits adriamycin-induced cardiac ferroptosis by enhancing Nrf2 signaling.Mol. Cell. Biochem.202147672603261110.1007/s11010‑021‑04112‑633656642
    [Google Scholar]
  183. NordgrenK.K.S. WallaceK.B. Disruption of the Keap1/Nrf2-antioxidant response system after chronic doxorubicin exposure in vivo.Cardiovasc. Toxicol.202020655757010.1007/s12012‑020‑09581‑732500386
    [Google Scholar]
  184. HuX. LiC. WangQ. WeiZ. ChenT. WangY. LiY. Dimethyl fumarate ameliorates doxorubicin-induced cardiotoxicity by activating the Nrf2 pathway.Front. Pharmacol.20221387205710.3389/fphar.2022.87205735559248
    [Google Scholar]
  185. WangY. YanS. LiuX. DengF. WangP. YangL. HuL. HuangK. HeJ. PRMT4 promotes ferroptosis to aggravate doxorubicin-induced cardiomyopathy via inhibition of the Nrf2/GPX4 pathway.Cell Death Differ.202229101982199510.1038/s41418‑022‑00990‑535383293
    [Google Scholar]
  186. LiuP. LiJ. LiuM. ZhangM. XueY. ZhangY. HanX. JingX. ChuL. Hesperetin modulates the Sirt1/Nrf2 signaling pathway in counteracting myocardial ischemia through suppression of oxidative stress, inflammation, and apoptosis.Biomed. Pharmacother.202113911155210.1016/j.biopha.2021.11155233839495
    [Google Scholar]
  187. WangW. ZhongX. FangZ. LiJ. LiH. LiuX. YuanX. HuangW. HuangZ. Cardiac sirtuin1 deficiency exacerbates ferroptosis in doxorubicin-induced cardiac injury through the Nrf2/Keap1 pathway.Chem. Biol. Interact.202337711046910.1016/j.cbi.2023.11046937030624
    [Google Scholar]
  188. DengJ. HuangM. WuH. Protective effect of limonin against doxorubicin-induced cardiotoxicity via activating nuclear factor - like 2 and sirtuin 2 signaling pathways.Bioengineered20211217975798410.1080/21655979.2021.198529934565300
    [Google Scholar]
  189. HouK. ShenJ. YanJ. ZhaiC. ZhangJ. PanJ.A. ZhangY. JiangY. WangY. LinR.Z. CongH. GaoS. ZongW.X. Loss of TRIM21 alleviates cardiotoxicity by suppressing ferroptosis induced by the chemotherapeutic agent doxorubicin.EBioMedicine20216910345610.1016/j.ebiom.2021.10345634233258
    [Google Scholar]
  190. HuX. LiuH. WangZ. HuZ. LiL. miR-200a attenuated doxorubicin-induced cardiotoxicity through upregulation of Nrf2 in mice.Oxid. Med. Cell. Longev.2019201911310.1155/2019/151232631781322
    [Google Scholar]
  191. ZhangW.B. LaiX. GuoX.F. Activation of Nrf2 by miR-152 inhibits doxorubicin-induced cardiotoxicity via attenuation of oxidative stress, inflammation, and apoptosis.Oxid. Med. Cell. Longev.202120211886088310.1155/2021/886088333574984
    [Google Scholar]
  192. ShiS. ChenY. LuoZ. NieG. DaiY. Role of oxidative stress and inflammation-related signaling pathways in doxorubicin-induced cardiomyopathy.Cell Commun. Signal.20232116110.1186/s12964‑023‑01077‑536918950
    [Google Scholar]
  193. QiW. BoliangW. XiaoxiT. GuoqiangF. JianboX. GangW. Cardamonin protects against doxorubicin-induced cardiotoxicity in mice by restraining oxidative stress and inflammation associated with Nrf2 signaling.Biomed. Pharmacother.202012210954710.1016/j.biopha.2019.10954731918264
    [Google Scholar]
  194. WangX. ChenL. WangT. JiangX. ZhangH. LiP. LvB. GaoX. Ginsenoside Rg3 antagonizes adriamycin-induced cardiotoxicity by improving endothelial dysfunction from oxidative stress via upregulating the Nrf2-ARE pathway through the activation of Akt.Phytomedicine2015221087588410.1016/j.phymed.2015.06.01026321736
    [Google Scholar]
  195. Al-KenanyS.A. Al-ShawiN.N. Protective effect of cafestol against doxorubicin-induced cardiotoxicity in rats by activating the Nrf2 pathway.Front. Pharmacol.202314120678210.3389/fphar.2023.120678237377932
    [Google Scholar]
  196. GuoZ. YanM. ChenL. FangP. LiZ. WanZ. CaoS. HouZ. WeiS. LiW. ZhangB. Nrf2‑dependent antioxidant response mediated the protective effect of tanshinone IIA on doxorubicin‑induced cardiotoxicity.Exp. Ther. Med.20181643333334410.3892/etm.2018.661430233680
    [Google Scholar]
  197. YuX. CuiL. ZhangZ. ZhaoQ. LiS. α-Linolenic acid attenuates doxorubicin-induced cardiotoxicity in rats through suppression of oxidative stress and apoptosis.Acta Biochim. Biophys. Sin.2013451081782610.1093/abbs/gmt08223896563
    [Google Scholar]
  198. KambleS.M. PatilC.R. Asiatic acid ameliorates doxorubicin-induced cardiac and hepato-renal toxicities with Nrf2 transcriptional factor activation in rats.Cardiovasc. Toxicol.201818213114110.1007/s12012‑017‑9424‑028856520
    [Google Scholar]
  199. ChengX. LiuD. XingR. SongH. TianX. YanC. HanY. Orosomucoid 1 attenuates doxorubicin-induced oxidative stress and apoptosis in cardiomyocytes via Nrf2 signaling.BioMed Res. Int.2020202011310.1155/2020/592357233134382
    [Google Scholar]
  200. SahuB.D. KumarJ.M. KunchaM. BorkarR.M. SrinivasR. SistlaR. Baicalein alleviates doxorubicin-induced cardiotoxicity via suppression of myocardial oxidative stress and apoptosis in mice.Life Sci.201614481810.1016/j.lfs.2015.11.01826606860
    [Google Scholar]
  201. ChenJ. ZhangS. PanG. LinL. LiuD. LiuZ. MeiS. ZhangL. HuZ. ChenJ. LuoH. WangY. XinY. YouZ. Modulatory effect of metformin on cardiotoxicity induced by doxorubicin via the MAPK and AMPK pathways.Life Sci.202024911749810.1016/j.lfs.2020.11749832142765
    [Google Scholar]
  202. ZhangY. AhmadK.A. KhanF.U. YanS. IhsanA.U. DingQ. Chitosan oligosaccharides prevent doxorubicin-induced oxidative stress and cardiac apoptosis through activating p38 and JNK MAPK mediated Nrf2/ARE pathway.Chem. Biol. Interact.2019305546510.1016/j.cbi.2019.03.02730928397
    [Google Scholar]
  203. ZhaoY.Q. ZhangL. ZhaoG.X. ChenY. SunK.L. WangB. Fucoxanthin attenuates doxorubicin-induced cardiotoxicity via anti-oxidant and anti-apoptotic mechanisms associated with p38, JNK and p53 pathways.J. Funct. Foods20196210354210.1016/j.jff.2019.103542
    [Google Scholar]
  204. GuoR. LinJ. XuW. ShenN. MoL. ZhangC. FengJ. Hydrogen sulfide attenuates doxorubicin-induced cardiotoxicity by inhibition of the p38 MAPK pathway in H9c2 cells.Int. J. Mol. Med.201331364465010.3892/ijmm.2013.124623338126
    [Google Scholar]
  205. WangX. WangX.L. ChenH.L. WuD. ChenJ.X. WangX.X. LiR.L. HeJ.H. MoL. CenX. WeiY.Q. JiangW. Ghrelin inhibits doxorubicin cardiotoxicity by inhibiting excessive autophagy through AMPK and p38-MAPK.Biochem. Pharmacol.201488333435010.1016/j.bcp.2014.01.04024522112
    [Google Scholar]
  206. SunJ. SunG. CuiX. MengX. QinM. SunX. Myricitrin protects against doxorubicin-induced cardiotoxicity by counteracting oxidative stress and inhibiting mitochondrial apoptosis via ERK/p53 pathway.Evid. Based Complement. Alternat. Med.201620161609378310.1155/2016/609378327703489
    [Google Scholar]
  207. MantawyE.M. EsmatA. El-BaklyW.M. Salah ElDinR.A. El-DemerdashE. Mechanistic clues to the protective effect of chrysin against doxorubicin-induced cardiomyopathy: Plausible roles of p53, MAPK and AKT pathways.Sci. Rep.201771479510.1038/s41598‑017‑05005‑928684738
    [Google Scholar]
  208. YaoH. ShangZ. WangP. LiS. ZhangQ. TianH. RenD. HanX. Protection of luteolin-7-O-glucoside against doxorubicin-induced injury through PTEN/Akt and ERK pathway in H9c2 cells.Cardiovasc. Toxicol.201616210111010.1007/s12012‑015‑9317‑z25724325
    [Google Scholar]
  209. KimD.S. KimH.R. WooE.R. HongS.T. ChaeH.J. ChaeS.W. Inhibitory effects of rosmarinic acid on adriamycin-induced apoptosis in H9c2 cardiac muscle cells by inhibiting reactive oxygen species and the activations of c-Jun N-terminal kinase and extracellular signal-regulated kinase.Biochem. Pharmacol.20057071066107810.1016/j.bcp.2005.06.02616102732
    [Google Scholar]
  210. LiuM.H. LinX.L. ZhangY. HeJ. TanT.P. WuS.J. LiuJ. TianW. ChenL. YuS. LiJ. YuanC. Hydrogen sulfide attenuates doxorubicin-induced cardiotoxicity by inhibiting reactive oxygen species-activated extracellular signal-regulated kinase 1/2 in H9c2 cardiac myocytes.Mol. Med. Rep.20151256841684810.3892/mmr.2015.423426299281
    [Google Scholar]
  211. XiaoJ. SunG.B. SunB. WuY. HeL. WangX. ChenR.C. CaoL. RenX.Y. SunX.B. Kaempferol protects against doxorubicin-induced cardiotoxicity in vivo and in vitro.Toxicology20122921536210.1016/j.tox.2011.11.01822155320
    [Google Scholar]
  212. ChenY.L. LohS.H. ChenJ.J. TsaiC.S. Urotensin II prevents cardiomyocyte apoptosis induced by doxorubicin via Akt and ERK.Eur. J. Pharmacol.20126801-3889410.1016/j.ejphar.2012.01.03422329895
    [Google Scholar]
  213. ArunachalamS. KimS.Y. LeeS.H. LeeY.H. KimM.S. YunB.S. YiH.K. HwangP.H. Davallialactone protects against adriamycin-induced cardiotoxicity in vitro and in vivo.J. Nat. Med.201266114915710.1007/s11418‑011‑0567‑121858697
    [Google Scholar]
  214. ShenW. HuangJ. WangY. Biological significance of NOTCH signaling strength.Front. Cell Dev. Biol.2021965227310.3389/fcell.2021.65227333842479
    [Google Scholar]
  215. MannanA. DhiamnS. GargN. SinghT.G. Pharmacological modulation of Sonic Hedgehog signaling pathways in Angiogenesis: A mechanistic perspective.Dev. Biol.2023504587410.1016/j.ydbio.2023.09.00937739118
    [Google Scholar]
  216. KopanR. Notch signaling.Cold Spring Harb. Perspect. Biol.2012410a01121310.1101/cshperspect.a01121323028119
    [Google Scholar]
  217. ZhouB. LinW. LongY. YangY. ZhangH. WuK. ChuQ. Notch signaling pathway: Architecture, disease, and therapeutics.Signal Transduct. Target. Ther.2022719510.1038/s41392‑022‑00934‑y35332121
    [Google Scholar]
  218. BrayS.J. Notch signalling: A simple pathway becomes complex.Nat. Rev. Mol. Cell Biol.20067967868910.1038/nrm200916921404
    [Google Scholar]
  219. MarracinoL. FortiniF. BouhamidaE. CamponogaraF. SeveriP. MazzoniE. PatergnaniS. D’AnielloE. CampanaR. PintonP. MartiniF. TognonM. CampoG. FerrariR. Vieceli Dalla SegaF. RizzoP. Adding a “Notch” to cardiovascular disease therapeutics: A microRNA-based approach.Front. Cell Dev. Biol.2021969511410.3389/fcell.2021.69511434527667
    [Google Scholar]
  220. BadrA.M. MahranY.F. Notch pathway and its role in the cardiovascular system.Syst. Rev. Pharm.20201110342349
    [Google Scholar]
  221. TimmermanL.A. Grego-BessaJ. RayaA. BertránE. Pérez-PomaresJ.M. DíezJ. ArandaS. PalomoS. McCormickF. Izpisúa-BelmonteJ.C. de la PompaJ.L. Notch promotes epithelial-mesenchymal transition during cardiac development and oncogenic transformation.Genes Dev.20041819911510.1101/gad.27630414701881
    [Google Scholar]
  222. ChenH. ShiS. AcostaL. LiW. LuJ. BaoS. ChenZ. YangZ. SchneiderM.D. ChienK.R. ConwayS.J. YoderM.C. HanelineL.S. FrancoD. ShouW. BMP10 is essential for maintaining cardiac growth during murine cardiogenesis.Development200413192219223110.1242/dev.0109415073151
    [Google Scholar]
  223. Grego-BessaJ. Luna-ZuritaL. del MonteG. BolósV. MelgarP. ArandillaA. GarrattA.N. ZangH. MukouyamaY. ChenH. ShouW. BallestarE. EstellerM. RojasA. Pérez-PomaresJ.M. de la PompaJ.L. Notch signaling is essential for ventricular chamber development.Dev. Cell200712341542910.1016/j.devcel.2006.12.01117336907
    [Google Scholar]
  224. ChenL. XiaW. HouM. Mesenchymal stem cells attenuate doxorubicin‑induced cellular senescence through the VEGF/Notch/TGF‑β signaling pathway in H9c2 cardiomyocytes.Int. J. Mol. Med.201842167468410.3892/ijmm.2018.363529693137
    [Google Scholar]
  225. CastañaresC. Redondo-HorcajoM. Magán-MarchalN. ten DijkeP. LamasS. Rodríguez-PascualF. Signaling by ALK5 mediates TGF-β-induced ET-1 expression in endothelial cells: A role for migration and proliferation.J. Cell Sci.200712071256126610.1242/jcs.0341917376964
    [Google Scholar]
  226. PackardR.R.S. BaekK.I. BeebeT. JenN. DingY. ShiF. FeiP. KangB.J. ChenP.H. GauJ. ChenM. TangJ.Y. ShihY.H. DingY. LiD. XuX. HsiaiT.K. Automated segmentation of light-sheet fluorescent imaging to characterize experimental doxorubicin-induced cardiac injury and repair.Sci. Rep.201771860310.1038/s41598‑017‑09152‑x28819303
    [Google Scholar]
  227. Thabassum Akhtar IqbalS. Tirupathi PichiahP.B. RajaS. ArunachalamS. Paeonol reverses adriamycin-induced cardiac pathological remodeling through Notch1 signaling reactivation in H9c2 cells and adult zebrafish heart.Chem. Res. Toxicol.202033231232310.1021/acs.chemrestox.9b0009331307187
    [Google Scholar]
  228. MacDonaldB.T. TamaiK. HeX. Wnt/beta-catenin signaling: Components, mechanisms, and diseases.Dev. Cell200917192610.1016/j.devcel.2009.06.01619619488
    [Google Scholar]
  229. SharmaV. SharmaP. SinghT.G. Wnt signalling pathways as mediators of neuroprotective mechanisms: Therapeutic implications in stroke.Mol. Biol. Rep.202451124710.1007/s11033‑023‑09202‑w38300425
    [Google Scholar]
  230. AkiyamaT. Wnt/β-catenin signaling.Cytokine Growth Factor Rev.200011427328210.1016/S1359‑6101(00)00011‑310959075
    [Google Scholar]
  231. NusseR. CleversH. Wnt/β-catenin signaling, disease, and emerging therapeutic modalities.Cell2017169698599910.1016/j.cell.2017.05.01628575679
    [Google Scholar]
  232. ZhangY. WangX. Targeting the Wnt/β-catenin signaling pathway in cancer.J. Hematol. Oncol.202013116510.1186/s13045‑020‑00990‑333276800
    [Google Scholar]
  233. CleversH. Wnt/beta-catenin signaling in development and disease.Cell2006127346948010.1016/j.cell.2006.10.01817081971
    [Google Scholar]
  234. HuangH. HeX. Wnt/β-catenin signaling: New (and old) players and new insights.Curr. Opin. Cell Biol.200820211912510.1016/j.ceb.2008.01.00918339531
    [Google Scholar]
  235. ChengW. CuiC. LiuG. YeC. ShaoF. BagchiA.K. MehtaJ.L. WangX. Nf-κb, a potential therapeutic target in cardiovascular diseases.Cardiovasc. Drugs Ther.202337357158410.1007/s10557‑022‑07362‑835796905
    [Google Scholar]
  236. RenD. LiF. CaoQ. GaoA. AiY. ZhangJ. Yangxin granules alleviate doxorubicin-induced cardiotoxicity by suppressing oxidative stress and apoptosis mediated by AKT/GSK3 β /β-catenin signaling.J. Int. Med. Res.202048810.1177/030006052094516132780664
    [Google Scholar]
  237. LiangL. TuY. LuJ. WangP. GuoZ. WangQ. GuoK. LanR. LiH. LiuP. Dkk1 exacerbates doxorubicin-induced cardiotoxicity by inhibiting the Wnt/β-catenin signaling pathway.J. Cell Sci.201913210jcs22847810.1242/jcs.22847831028181
    [Google Scholar]
  238. CaoY.J. LiJ.Y. WangP.X. LinZ.R. YuW.J. ZhangJ.G. LuJ. LiuP.Q. PKC-ζ aggravates doxorubicin-induced cardiotoxicity by inhibiting Wnt/β-catenin signaling.Front. Pharmacol.20221379843610.3389/fphar.2022.79843635237161
    [Google Scholar]
  239. XieZ. XiaW. HouM. Long intergenic non‑coding RNA‑p21 mediates cardiac senescence via the Wnt/β‑catenin signaling pathway in doxorubicin-induced cardiotoxicity.Mol. Med. Rep.20181722695270429207090
    [Google Scholar]
  240. FengD. LiJ. GuoL. LiuJ. WangS. MaX. SongY. LiuJ. HaoE. DDX3X alleviates doxorubicin‐induced cardiotoxicity by regulating Wnt/β‐catenin signaling pathway in an in vitro model.J. Biochem. Mol. Toxicol.2022368e2307710.1002/jbt.2307735467791
    [Google Scholar]
  241. YinC. RehmanS. KukrejaR.C. XiL. Abstract 12237: Upregulation of cardiac microRNA 34a, sirt1, and notch1 following oral ingestion of beetroot juice and doxorubicin treatment: A novel protective signaling against cardiotoxicity.Circulation2014130Suppl. 2A12237A12237
    [Google Scholar]
  242. El-ElaS.R.A. ZaghloulR.A. EissaL.A. Promising cardioprotective effect of baicalin in doxorubicin-induced cardiotoxicity through targeting toll-like receptor 4/nuclear factor-κB and Wnt/β-catenin pathways.Nutrition202210211173210.1016/j.nut.2022.11173235816809
    [Google Scholar]
  243. SadikN.A.H. ShakerO.G. GhanemH.Z. HassanH.A. Abdel-HamidA.H.Z. Single-nucleotide polymorphism of Toll-like receptor 4 and interleukin-10 in response to interferon-based therapy in Egyptian chronic hepatitis C patients.Arch. Virol.201516092181219510.1007/s00705‑015‑2493‑026095186
    [Google Scholar]
  244. XinyongC. ZhiyiZ. LangH. PengY. XiaochengW. PingZ. LiangS. The role of toll-like receptors in myocardial toxicity induced by doxorubicin.Immunol. Lett.2020217566410.1016/j.imlet.2019.11.00131707054
    [Google Scholar]
  245. DelnesteY. BeauvillainC. JeanninP. [Innate immunity: Structure and function of TLRs].Med. Sci. (Paris)2007231677310.1051/medsci/20072316717212934
    [Google Scholar]
  246. El-ZayatS.R. SibaiiH. MannaaF.A. Toll-like receptors activation, signaling, and targeting: An overview.Bull. Natl. Res. Cent.201943118710.1186/s42269‑019‑0227‑2
    [Google Scholar]
  247. BehlT. KumarK. BriscC. RusM. Nistor-CseppentoD.C. BusteaC. AronR.A.C. PantisC. ZenginG. SehgalA. KaurR. KumarA. AroraS. SetiaD. ChandelD. BungauS. Exploring the multifocal role of phytochemicals as immunomodulators.Biomed. Pharmacother.202113311095910.1016/j.biopha.2020.11095933197758
    [Google Scholar]
  248. ZhangY. WuJ. DongE. WangZ. XiaoH. Toll-like receptors in cardiac hypertrophy.Front. Cardiovasc. Med.202310114358310.3389/fcvm.2023.114358337113698
    [Google Scholar]
  249. FrantzS. KellyR.A. BourcierT. Role of TLR-2 in the activation of nuclear factor kappaB by oxidative stress in cardiac myocytes.J. Biol. Chem.200127675197520310.1074/jbc.M00916020011083876
    [Google Scholar]
  250. LiangS. XinyongC. HongminZ. JingW. LangH. PingZ. TLR2 and TLR3 expression as a biomarker for the risk of doxorubicin-induced heart failure.Toxicol. Lett.201829520521110.1016/j.toxlet.2018.06.121929959987
    [Google Scholar]
  251. NozakiN. ShishidoT. TakeishiY. KubotaI. Modulation of doxorubicin-induced cardiac dysfunction in toll-like receptor-2-knockout mice.Circulation2004110182869287410.1161/01.CIR.0000146889.46519.2715505089
    [Google Scholar]
  252. RiadA. BienS. GratzM. EscherF. HeimesaatM.M. BereswillS. KriegT. FelixS.B. SchultheissH.P. KroemerH.K. TschöpeC. TschöpeC. Toll‐like receptor‐4 deficiency attenuates doxorubicin‐induced cardiomyopathy in mice.Eur. J. Heart Fail.200810323324310.1016/j.ejheart.2008.01.00418321777
    [Google Scholar]
  253. SumneangN. TanajakP. OoT.T. Toll-like receptor 4 inflammatory perspective on doxorubicin-induced cardiotoxicity.Molecules20232811429410.3390/molecules2811429437298770
    [Google Scholar]
  254. MaZ.G. KongC.Y. WuH.M. SongP. ZhangX. YuanY.P. DengW. TangQ.Z. Toll-like receptor 5 deficiency diminishes doxorubicin-induced acute cardiotoxicity in mice.Theranostics20201024110131102510.7150/thno.4751633042267
    [Google Scholar]
  255. GuoZ. TangN. LiuF.Y. YangZ. MaS.Q. AnP. WuH.M. FanD. TangQ.Z. TLR9 deficiency alleviates doxorubicin‐induced cardiotoxicity via the regulation of autophagy.J. Cell. Mol. Med.20202418109131092310.1111/jcmm.1571933140921
    [Google Scholar]
  256. KumarP. KumarM. BediO. GuptaM. KumarS. JaiswalG. RahiV. YedkeN.G. BijalwanA. SharmaS. JamwalS. Role of vitamins and minerals as immunity boosters in COVID-19.Inflammopharmacology20212941001101610.1007/s10787‑021‑00826‑734110533
    [Google Scholar]
  257. RehniA.K. BhatejaP. SinghT.G. SinghN. Nuclear factor-κ-B inhibitor modulates the development of opioid dependence in a mouse model of naloxone-induced opioid withdrawal syndrome.Behav. Pharmacol.2008193265269https://journals.lww.com/behaviouralpharm/abstract/2008/05000/nuclear_factor___b_inhibitor_modulates_the.11.aspx10.1097/FBP.0b013e3282febcd918469544
    [Google Scholar]
  258. LiuT. ZhangL. JooD. SunS.C. NF-κB signaling in inflammation.Signal Transduct. Target. Ther.2017211702310.1038/sigtrans.2017.2329158945
    [Google Scholar]
  259. AlbensiB.C. What is nuclear factor kappa B (NF-κB) doing in and to the mitochondrion?Front. Cell Dev. Biol.2019715410.3389/fcell.2019.0015431448275
    [Google Scholar]
  260. SolimanN.A. Abo El GheitR.E. Abdel GhafarM.T. AbuoHashishN.A. IbrahimM.A.A. Abo SafiaH.S. El-SakaM.H. ElshamyA.M. Unraveling the biomechanistic role of Rac1/TWEAK/Fn14/NF‐κB intricate network in experimentally doxorubicin‐induced cardiotoxicity in rats: The role of curcumin.J. Biochem. Mol. Toxicol.2021358e2282910.1002/jbt.2282934047412
    [Google Scholar]
  261. El-BaklyW.M. LoukaM.L. El-HalawanyA.M. SchaalanM.F. 6-gingerol ameliorated doxorubicin-induced cardiotoxicity: Role of nuclear factor kappa B and protein glycation.Cancer Chemother. Pharmacol.201270683384110.1007/s00280‑012‑1975‑y23014738
    [Google Scholar]
  262. Bin JardanY.A. AnsariM.A. RaishM. AlkharfyK.M. AhadA. Al-JenoobiF.I. HaqN. KhanM.R. AhmadA. Sinapic acid ameliorates oxidative stress, inflammation, and apoptosis in acute doxorubicin-induced cardiotoxicity via the NF-κB-mediated pathway.BioMed Res. Int.2020202011010.1155/2020/392179632258120
    [Google Scholar]
  263. HafezH.M. HassaneinH. Montelukast ameliorates doxorubicin-induced cardiotoxicity via modulation of p-glycoprotein and inhibition of ROS-mediated TNF-α/NF-κB pathways.Drug Chem. Toxicol.202245254855910.1080/01480545.2020.173088532106718
    [Google Scholar]
  264. ImamF. Al-HarbiN.O. Al-HarbiM.M. AnsariM.A. Al-AsmariA.F. AnsariM.N. Al-AnaziW.A. BahashwanS. AlmutairiM.M. AlshammariM. KhanM.R. AlsaadA.M. AlotaibiM.R. Apremilast prevent doxorubicin-induced apoptosis and inflammation in heart through inhibition of oxidative stress mediated activation of NF-κB signaling pathways.Pharmacol. Rep.2018705993100010.1016/j.pharep.2018.03.00930118964
    [Google Scholar]
  265. AlzokakyA.A. Al-KarmalawyA.A. SalehM.A. AbdoW. FarageA.E. BelalA. AbourehabM.A.S. AntarS.A. Metformin ameliorates doxorubicin-induced cardiotoxicity targeting HMGB1/TLR4/NLRP3 signaling pathway in mice.Life Sci.202331612139010.1016/j.lfs.2023.12139036649752
    [Google Scholar]
  266. SafaeianL. BaniahmadB. VaseghiG. RabbaniM. MohammadiB. Cardioprotective effect of vanillic acid against doxorubicin-induced cardiotoxicity in rat.Res. Pharm. Sci.2020151879610.4103/1735‑5362.27871832180820
    [Google Scholar]
  267. MaS. LiX. DongL. ZhuJ. ZhangH. JiaY. Protective effect of Sheng-Mai Yin, a traditional Chinese preparation, against doxorubicin-induced cardiac toxicity in rats.BMC Complement. Altern. Med.20161616110.1186/s12906‑016‑1037‑926865364
    [Google Scholar]
  268. RefaieM.M.M. ShehataS. IbrahimR.A. BayoumiA.M.A. Abdel-GaberS.A. Dose-dependent cardioprotective effect of hemin in doxorubicin-induced cardiotoxicity via Nrf2/HO-1 and TLR-5/NF-κB/TNF-α signaling pathways.Cardiovasc. Toxicol.202121121033104410.1007/s12012‑021‑09694‑734510376
    [Google Scholar]
  269. AlanaziA.M. FaddaL. AlhusainiA. AhmadR. HasanI.H. MahmoudA.M. Liposomal resveratrol and/or carvedilol attenuate doxorubicin-induced cardiotoxicity by modulating inflammation, oxidative stress, and S100A1 in rats.Antioxidants20209215910.3390/antiox902015932079097
    [Google Scholar]
  270. ZhangZ. PengJ. HuY. ZengG. DuW. ShenC. CTRP5 attenuates doxorubicin-induced cardiotoxicity via inhibiting TLR4/NLRP3 signaling.Cardiovasc. Drugs Ther.202311010.1007/s10557‑023‑07464‑x37256416
    [Google Scholar]
  271. KohJ.S. YiC. HeoR.W. AhnJ.W. ParkJ.R. LeeJ.E. KimJ.H. HwangJ.Y. RohG.S. Protective effect of cilostazol against doxorubicin-induced cardiomyopathy in mice.Free Radic. Biol. Med.201589546110.1016/j.freeradbiomed.2015.07.01626191652
    [Google Scholar]
  272. YeS. SuL. ShanP. YeB. WuS. LiangG. HuangW. LCZ696 attenuates doxorubicin-induced chronic cardiomyopathy through the TLR2-MyD88 complex formation.Front. Cell Dev. Biol.2021965405110.3389/fcell.2021.65405133928085
    [Google Scholar]
  273. FengP. YangY. LiuN. WangS. Baicalin regulates TLR4/IκBα/NFκB signaling pathway to alleviate inflammation in Doxorubicin related cardiotoxicity.Biochem. Biophys. Res. Commun.20226371810.1016/j.bbrc.2022.10.06136375245
    [Google Scholar]
  274. ChuX. ZhangY. XueY. LiZ. ShiJ. WangH. ChuL. Crocin protects against cardiotoxicity induced by doxorubicin through TLR-2/NF-κB signal pathway in vivo and in vitro.Int. Immunopharmacol.20208410654810.1016/j.intimp.2020.10654832388215
    [Google Scholar]
  275. EzzatS.M. El GaafaryM. El SayedA.M. SabryO.M. AliZ.Y. HafnerS. SchmiechM. JinL. SyrovetsT. SimmetT. The cardenolide glycoside acovenoside A affords protective activity in doxorubicin-induced cardiotoxicity in mice.J. Pharmacol. Exp. Ther.2016358226227010.1124/jpet.116.23265227247000
    [Google Scholar]
  276. Ibrahim FouadG. AhmedK.A. Curcumin ameliorates doxorubicin-induced cardiotoxicity and hepatotoxicity via suppressing oxidative stress and modulating iNOS, NF-κB, and TNF-α in rats.Cardiovasc. Toxicol.202222215216610.1007/s12012‑021‑09710‑w34837640
    [Google Scholar]
  277. LinM. YinM. Preventive effects of ellagic acid against doxorubicin-induced cardio-toxicity in mice.Cardiovasc. Toxicol.201313318519310.1007/s12012‑013‑9197‑z23322372
    [Google Scholar]
  278. ZhangJ. CuiL. HanX. ZhangY. ZhangX. ChuX. ZhangF. ZhangY. ChuL. Protective effects of tannic acid on acute doxorubicin-induced cardiotoxicity: Involvement of suppression in oxidative stress, inflammation, and apoptosis.Biomed. Pharmacother.2017931253126010.1016/j.biopha.2017.07.05128738542
    [Google Scholar]
  279. ChenC.T. WangZ.H. HsuC.C. LinH.H. ChenJ.H. In vivo protective effects of diosgenin against doxorubicin-induced cardiotoxicity.Nutrients2015764938495410.3390/nu706493826091236
    [Google Scholar]
  280. El-SaidN.T. MohamedE.A. TahaR.A. Irbesartan suppresses cardiac toxicity induced by doxorubicin via regulating the p38-MAPK/NF-κB and TGF-β1 pathways.Naunyn Schmiedebergs Arch. Pharmacol.2019392664765810.1007/s00210‑019‑01624‑330734091
    [Google Scholar]
  281. El-AgamyD.S. IbrahimS.R.M. AhmedN. KhoshhalS. Abo-HadedH.M. ElkablawyM.A. AljuhaniN. MohamedG.A. Aspernolide F, as a new cardioprotective butyrolactone against doxorubicin-induced cardiotoxicity.Int. Immunopharmacol.20197242943610.1016/j.intimp.2019.04.04531030099
    [Google Scholar]
  282. ZhangX.J. JiangD.S. LiH. The interferon regulatory factors as novel potential targets in the treatment of cardiovascular diseases.Br. J. Pharmacol.2015172235457547610.1111/bph.1288125131895
    [Google Scholar]
  283. JefferiesC.A. Regulating IRFs in IFN driven disease.Front. Immunol.20191032510.3389/fimmu.2019.0032530984161
    [Google Scholar]
  284. ZhangX.J. ZhangP. LiH. Interferon regulatory factor signalings in cardiometabolic diseases.Hypertension201566222224710.1161/HYPERTENSIONAHA.115.0489826077571
    [Google Scholar]
  285. DecoutA. KatzJ.D. VenkatramanS. AblasserA. The cGAS–STING pathway as a therapeutic target in inflammatory diseases.Nat. Rev. Immunol.202121954856910.1038/s41577‑021‑00524‑z33833439
    [Google Scholar]
  286. LuoW. ZouX. WangY. DongZ. WengX. PeiZ. SongS. ZhaoY. WeiZ. GaoR. ZhangB. LiuL. BaiP. LiuJ. WangX. GaoT. ZhangY. SunX. ChenH. HuK. DuS. SunA. GeJ. Critical role of the cGAS-STING pathway in doxorubicin-induced cardiotoxicity.Circ. Res.202313211e223e24210.1161/CIRCRESAHA.122.32158737154056
    [Google Scholar]
  287. NiC. MaP. WangR. LouX. LiuX. QinY. XueR. BlasigI. ErbenU. QinZ. Doxorubicin‐induced cardiotoxicity involves IFNγ‐mediated metabolic reprogramming in cardiomyocytes.J. Pathol.2019247332033210.1002/path.519230426505
    [Google Scholar]
  288. MaP. QinY. CaoH. ErbenU. NiC. QinZ. Temporary blockade of interferon-γ ameliorates doxorubicin-induced cardiotoxicity without influencing the anti-tumor effect.Biomed. Pharmacother.202013011058710.1016/j.biopha.2020.11058732763819
    [Google Scholar]
  289. TsuchiyaY. NakabayashiO. NakanoH. Flip the switch: Regulation of apoptosis and necroptosis by cFLIP.Int. J. Mol. Sci.20151612303213034110.3390/ijms16122623226694384
    [Google Scholar]
  290. WangN. GuanP. ZhangJ.P. ChangY.Z. GuL.J. HaoF. ShiZ.H. WangF.Y. ChuL. Preventive effects of fasudil on adriamycin-induced cardiomyopathy: Possible involvement of inhibition of RhoA/ROCK pathway.Food Chem. Toxicol.201149112975298210.1016/j.fct.2011.06.08021803115
    [Google Scholar]
  291. KruegerA. BaumannS. KrammerP.H. KirchhoffS. FLICE-inhibitory proteins: Regulators of death receptor-mediated apoptosis.Mol. Cell. Biol.200121248247825410.1128/MCB.21.24.8247‑8254.200111713262
    [Google Scholar]
  292. MizushimaN. LevineB. Autophagy in mammalian development and differentiation.Nat. Cell Biol.201012982383010.1038/ncb0910‑82320811354
    [Google Scholar]
  293. SafaA.R Roles of c-FLIP in apoptosis, necroptosis, and autophagy.J. Carcinog. Mutagen2013Suppl 6003003
    [Google Scholar]
  294. LiY.Z. WuH. LiuD. YangJ. YangJ. DingJ.W. ZhouG. ZhangJ. ZhangD. cFLIP-L alleviates myocardial ischemia-reperfusion injury by inhibiting endoplasmic reticulum stress.Cardiovasc. Drugs Ther.202337222523810.1007/s10557‑021‑07280‑134767133
    [Google Scholar]
  295. RasperD.M. VaillancourtJ.P. HadanoS. HoutzagerV.M. SeidenI. KeenS.L.C. TawaP. XanthoudakisS. NasirJ. MartindaleD. KoopB.F. PetersonE.P. ThornberryN.A. HuangJ. MacPhersonD.P. BlackS.C. HornungF. LenardoM.J. HaydenM.R. RoyS. NicholsonD.W. Cell death attenuation by ‘Usurpin’, a mammalian DED-caspase homologue that precludes caspase-8 recruitment and activation by the CD-95 (Fas, APO-1) receptor complex.Cell Death Differ.19985427128810.1038/sj.cdd.440037010200473
    [Google Scholar]
  296. MicheauO. Cellular FLICE-inhibitory protein: An attractive therapeutic target?Expert Opin. Ther. Targets20037455957310.1517/14728222.7.4.55912885274
    [Google Scholar]
  297. NitobeJ. YamaguchiS. OkuyamaM. NozakiN. SataM. MiyamotoT. TakeishiY. KubotaI. TomoikeH. Reactive oxygen species regulate FLICE inhibitory protein (FLIP) and susceptibility to Fas-mediated apoptosis in cardiac myocytes.Cardiovasc. Res.200357111912810.1016/S0008‑6363(02)00646‑612504821
    [Google Scholar]
  298. JangY.M. KendaiahS. DrewB. PhillipsT. SelmanC. JulianD. LeeuwenburghC. Doxorubicin treatment in vivo activates caspase‐12 mediated cardiac apoptosis in both male and female rats.FEBS Lett.2004577348349010.1016/j.febslet.2004.10.05315556633
    [Google Scholar]
  299. ReeveJ.L.V. SzegezdiE. LogueS.E. ChonghaileT.N. O’BrienT. RitterT. SamaliA. Distinct mechanisms of cardiomyocyte apoptosis induced by doxorubicin and hypoxia converge on mitochondria and are inhibited by Bcl‐xL.J. Cell. Mol. Med.200711350952010.1111/j.1582‑4934.2007.00042.x17635642
    [Google Scholar]
  300. SmythP. SesslerT. ScottC.J. LongleyD.B. FLIP(L): The pseudo‐caspase.FEBS J.2020287194246426010.1111/febs.1526032096279
    [Google Scholar]
  301. NakanoH. PiaoX. ShindoR. Komazawa-SakonS. Cellular FLICE-inhibitory protein regulates tissue homeostasis.Curr. Top. Microbiol. Immunol.201540311914110.1007/82_2015_44826160013
    [Google Scholar]
  302. DhanasekaranA. GruenlohS.K. BuonaccorsiJ.N. ZhangR. GrossG.J. FalckJ.R. PatelP.K. JacobsE.R. MedhoraM. Multiple antiapoptotic targets of the PI3K/Akt survival pathway are activated by epoxyeicosatrienoic acids to protect cardiomyocytes from hypoxia/anoxia.Am. J. Physiol. Heart Circ. Physiol.20082942H724H73510.1152/ajpheart.00979.200718055514
    [Google Scholar]
  303. PiacentinoV.III MilanoC.A. BolanosM. SchroderJ. MessinaE. CockrellA.S. JonesE. KrolA. BursacN. MaoL. DeviG.R. SamulskiR.J. BowlesD.E. X-linked inhibitor of apoptosis protein-mediated attenuation of apoptosis, using a novel cardiac-enhanced adeno-associated viral vector.Hum. Gene Ther.201223663564610.1089/hum.2011.18622339372
    [Google Scholar]
  304. WangJ. DongG. ChiW. NieY. MiR-96 promotes myocardial infarction-induced apoptosis by targeting XIAP.Biomed. Pharmacother.202113811120810.1016/j.biopha.2020.11120833752931
    [Google Scholar]
  305. SongZ. AnL. YeY. WuJ. ZouY. HeL. ZhuH. Essential role for UVRAG in autophagy and maintenance of cardiac function.Cardiovasc. Res.20141011485610.1093/cvr/cvt22324081163
    [Google Scholar]
  306. AnL. HuX. ZhangS. HuX. SongZ. NazA. ZiZ. WuJ. LiC. ZouY. HeL. ZhuH. UVRAG deficiency exacerbates doxorubicin-induced cardiotoxicity.Sci. Rep.2017714325110.1038/srep4325128225086
    [Google Scholar]
  307. LahalleA. LacroixM. De BlasioC. CisséM.Y. LinaresL.K. Le CamL. The p53 pathway and metabolism: The tree that hides the forest.Cancers202113113310.3390/cancers1301013333406607
    [Google Scholar]
  308. TasdemirE. MaiuriM.C. GalluzziL. VitaleI. Djavaheri-MergnyM. D’AmelioM. CriolloA. MorselliE. ZhuC. HarperF. NannmarkU. SamaraC. PintonP. VicencioJ.M. CarnuccioR. MollU.M. MadeoF. Paterlini-BrechotP. RizzutoR. SzabadkaiG. PierronG. BlomgrenK. TavernarakisN. CodognoP. CecconiF. KroemerG. Regulation of autophagy by cytoplasmic p53.Nat. Cell Biol.200810667668710.1038/ncb173018454141
    [Google Scholar]
  309. MaiuriM.C. GalluzziL. MorselliE. KeppO. MalikS.A. KroemerG. Autophagy regulation by p53.Curr. Opin. Cell Biol.201022218118510.1016/j.ceb.2009.12.00120044243
    [Google Scholar]
  310. LevineB. AbramsJ. p53: The Janus of autophagy?Nat. Cell Biol.200810663763910.1038/ncb0608‑63718521069
    [Google Scholar]
  311. GuoY. TangY. LuG. GuJ. p53 at the crossroads between doxorubicin-induced cardiotoxicity and resistance: A nutritional balancing act.Nutrients20231510225910.3390/nu1510225937242146
    [Google Scholar]
  312. FengX. LiuX. ZhangW. XiaoW. p53 directly suppresses BNIP3 expression to protect against hypoxia-induced cell death.EMBO J.201130163397341510.1038/emboj.2011.24821792176
    [Google Scholar]
  313. ShizukudaY. MatobaS. MianO.Y. NguyenT. HwangP.M. Targeted disruption of p53 attenuates doxorubicin-induced cardiac toxicity in mice.Mol. Cell. Biochem.20052731-2253210.1007/s11010‑005‑5905‑816013437
    [Google Scholar]
  314. McSweeneyK.M. BozzaW.P. AlterovitzW.L. ZhangB. Transcriptomic profiling reveals p53 as a key regulator of doxorubicin-induced cardiotoxicity.Cell Death Discov.20195110210.1038/s41420‑019‑0182‑631231550
    [Google Scholar]
  315. SardãoV.A. OliveiraP.J. HolyJ. OliveiraC.R. WallaceK.B. Doxorubicin-induced mitochondrial dysfunction is secondary to nuclear p53 activation in H9c2 cardiomyoblasts.Cancer Chemother. Pharmacol.200964481182710.1007/s00280‑009‑0932‑x19184017
    [Google Scholar]
  316. GhoshJ. DasJ. MannaP. SilP.C. The protective role of arjunolic acid against doxorubicin induced intracellular ROS dependent JNK-p38 and p53-mediated cardiac apoptosis.Biomaterials201132214857486610.1016/j.biomaterials.2011.03.04821486680
    [Google Scholar]
  317. KhafagaA.F. El-SayedY.S. All-trans-retinoic acid ameliorates doxorubicin-induced cardiotoxicity: in vivo potential involvement of oxidative stress, inflammation, and apoptosis via caspase-3 and p53 down-expression.Naunyn Schmiedebergs Arch. Pharmacol.20183911597010.1007/s00210‑017‑1437‑529085977
    [Google Scholar]
  318. RawlingsJ.S. RoslerK.M. HarrisonD.A. The JAK/STAT signaling pathway.J. Cell Sci.200411781281128310.1242/jcs.0096315020666
    [Google Scholar]
  319. MurrayP.J. The JAK-STAT signaling pathway: Input and output integration.J. Immunol.200717852623262910.4049/jimmunol.178.5.262317312100
    [Google Scholar]
  320. HuX. liJ. FuM. ZhaoX. WangW. The JAK/STAT signaling pathway: From bench to clinic.Signal Transduct. Target. Ther.20216140210.1038/s41392‑021‑00791‑134824210
    [Google Scholar]
  321. XinP. XuX. DengC. LiuS. WangY. ZhouX. MaH. WeiD. SunS. The role of JAK/STAT signaling pathway and its inhibitors in diseases.Int. Immunopharmacol.20208010621010.1016/j.intimp.2020.10621031972425
    [Google Scholar]
  322. MalemudC. PearlmanE. Targeting JAK/STAT signaling pathway in inflammatory diseases.Curr. Signal Transduct. Ther.20094320122110.2174/157436209789057467
    [Google Scholar]
  323. SeifF. KhoshmirsafaM. AazamiH. MohsenzadeganM. SedighiG. BaharM. The role of JAK-STAT signaling pathway and its regulators in the fate of T helper cells.Cell Commun. Signal.20171512310.1186/s12964‑017‑0177‑y28637459
    [Google Scholar]
  324. MalemudC.J. The role of the JAK/STAT signal pathway in rheumatoid arthritis.Ther. Adv. Musculoskelet. Dis.2018105-611712710.1177/1759720X1877622429942363
    [Google Scholar]
  325. BarryS.P. TownsendP.A. LatchmanD.S. StephanouA. Role of the JAK–STAT pathway in myocardial injury.Trends Mol. Med.2007132828910.1016/j.molmed.2006.12.00217194625
    [Google Scholar]
  326. LiW. QuX. KangX. ZhangH. ZhangX. HuH. YaoL. ZhangL. ZhengJ. ZhengY. ZhangJ. XuY. Silibinin eliminates mitochondrial ROS and restores autophagy through IL6ST/JAK2/STAT3 signaling pathway to protect cardiomyocytes from doxorubicin-induced injury.Eur. J. Pharmacol.202292917515310.1016/j.ejphar.2022.17515335839932
    [Google Scholar]
  327. OkparaE.S. AdedaraI.A. GuoX. KlosM.L. FarombiE.O. HanS. Molecular mechanisms associated with the chemoprotective role of protocatechuic acid and its potential benefits in the amelioration of doxorubicin-induced cardiotoxicity: A review.Toxicol. Rep.202291713172410.1016/j.toxrep.2022.09.00136561952
    [Google Scholar]
  328. ZhangJ. SunZ. LinN. LuW. HuangX. WengJ. SunS. ZhangC. YangQ. ZhouG. GuoH. ChiJ. Fucoidan from Fucus vesiculosus attenuates doxorubicin-induced acute cardiotoxicity by regulating JAK2/STAT3-mediated apoptosis and autophagy.Biomed. Pharmacother.202013011053410.1016/j.biopha.2020.11053432711244
    [Google Scholar]
  329. MascarenoE. El-ShafeiM. MaulikN. SatoM. GuoY. DasD.K. SiddiquiM.A.Q. JAK/STAT signaling is associated with cardiac dysfunction during ischemia and reperfusion.Circulation2001104332532910.1161/01.CIR.104.3.32511457752
    [Google Scholar]
  330. PangQ. YouL. MengX. LiY. DengT. LiD. ZhuB. Regulation of the JAK/STAT signaling pathway: The promising targets for cardiovascular disease.Biochem. Pharmacol.202321311558710.1016/j.bcp.2023.11558737187275
    [Google Scholar]
  331. FranchiL. EigenbrodT. Muñoz-PlanilloR. NuñezG. The inflammasome: A caspase-1-activation platform that regulates immune responses and disease pathogenesis.Nat. Immunol.200910324124710.1038/ni.170319221555
    [Google Scholar]
  332. ButtsB. GaryR.A. DunbarS.B. ButlerJ. The importance of NLRP3 inflammasome in heart failure.J. Card. Fail.201521758659310.1016/j.cardfail.2015.04.01425982825
    [Google Scholar]
  333. MaayahZ.H. TakaharaS. DyckJ.R.B. The beneficial effects of reducing NLRP3 inflammasome activation in the cardiotoxicity and the anti-cancer effects of doxorubicin.Arch. Toxicol.20219511910.1007/s00204‑020‑02876‑232852568
    [Google Scholar]
  334. SunZ. LuW. LinN. LinH. ZhangJ. NiT. MengL. ZhangC. GuoH. Dihydromyricetin alleviates doxorubicin-induced cardiotoxicity by inhibiting NLRP3 inflammasome through activation of SIRT1.Biochem. Pharmacol.202017511388810.1016/j.bcp.2020.11388832112883
    [Google Scholar]
  335. HuangP.P. FuJ. LiuL.H. WuK.F. LiuH.X. QiB.M. LiuY. QiB.L. Honokiol antagonizes doxorubicin‑induced cardiomyocyte senescence by inhibiting TXNIP‑mediated NLRP3 inflammasome activation.Int. J. Mol. Med.202045118619431746354
    [Google Scholar]
  336. YangH.B. LuZ.Y. YuanW. LiW.D. MaoS. Selenium attenuates doxorubicin-induced cardiotoxicity through Nrf2-NLRP3 pathway.Biol. Trace Elem. Res.202220062848285610.1007/s12011‑021‑02891‑z34462843
    [Google Scholar]
  337. KobayashiM. UsuiF. KarasawaT. KawashimaA. KimuraH. MizushinaY. ShirasunaK. MizukamiH. KasaharaT. HasebeN. TakahashiM. NLRP3 deficiency reduces macrophage interleukin-10 production and enhances the susceptibility to doxorubicin-induced cardiotoxicity.Sci. Rep.2016612648910.1038/srep2648927225830
    [Google Scholar]
  338. ZhangL. JiangY.H. FanC. ZhangQ. JiangY.H. LiY. XueY.T. MCC950 attenuates doxorubicin-induced myocardial injury in vivo and in vitro by inhibiting NLRP3-mediated pyroptosis.Biomed. Pharmacother.202114311213310.1016/j.biopha.2021.11213334474337
    [Google Scholar]
  339. WeiS. MaW. LiX. JiangC. SunT. LiY. ZhangB. LiW. Involvement of ROS/NLRP3 inflammasome signaling pathway in doxorubicin-induced cardiotoxicity.Cardiovasc. Toxicol.202020550751910.1007/s12012‑020‑09576‑432607760
    [Google Scholar]
  340. SunZ. FangC. XuS. WangB. LiD. LiuX. MiY. GuoH. JiangJ. SIRT3 attenuates doxorubicin-induced cardiotoxicity by inhibiting NLRP3 inflammasome via autophagy.Biochem. Pharmacol.202320711535410.1016/j.bcp.2022.11535436435202
    [Google Scholar]
  341. ParkS. ShinJ. BaeJ. HanD. ParkS.R. ShinJ. LeeS.K. ParkH.W. SIRT1 alleviates LPS-induced IL-1β production by suppressing NLRP3 inflammasome activation and ROS production in trophoblasts.Cells20209372810.3390/cells903072832188057
    [Google Scholar]
  342. LiuJ. JinY. WangB. WangY. ZuoS. ZhangJ. Dopamine D1 receptor alleviates doxorubicin-induced cardiac injury by inhibiting NLRP3 inflammasome.Biochem. Biophys. Res. Commun.202156171310.1016/j.bbrc.2021.04.09833992835
    [Google Scholar]
  343. YoshidaM. ShiojimaI. IkedaH. KomuroI. Chronic doxorubicin cardiotoxicity is mediated by oxidative DNA damage-ATM-p53-apoptosis pathway and attenuated by pitavastatin through the inhibition of Rac1 activity.J. Mol. Cell. Cardiol.200947569870510.1016/j.yjmcc.2009.07.02419660469
    [Google Scholar]
  344. JohnsonR. ShabalalaS. LouwJ. KappoA. MullerC. Aspalathin reverts doxorubicin-induced cardiotoxicity through increased autophagy and decreased expression of p53/mTOR/p62 signaling.Molecules20172210158910.3390/molecules2210158928937626
    [Google Scholar]
  345. ThandavarayanR.A. GiridharanV.V. ArumugamS. SuzukiK. KoK.M. KrishnamurthyP. WatanabeK. KonishiT. Schisandrin B prevents doxorubicin induced cardiac dysfunction by modulation of DNA damage, oxidative stress and inflammation through inhibition of MAPK/p53 signaling.PLoS One2015103e011921410.1371/journal.pone.011921425742619
    [Google Scholar]
  346. PanJ.A. TangY. YuJ.Y. ZhangH. ZhangJ.F. WangC.Q. GuJ. miR-146a attenuates apoptosis and modulates autophagy by targeting TAF9b/P53 pathway in doxorubicin-induced cardiotoxicity.Cell Death Dis.201910966810.1038/s41419‑019‑1901‑x31511497
    [Google Scholar]
  347. MaayahZ.H. AlamA.S. TakaharaS. SoniS. FerdaoussiM. MatsumuraN. ZordokyB.N. EisenstatD.D. DyckJ.R.B. Resveratrol reduces cardiac NLRP3‐inflammasome activation and systemic inflammation to lessen doxorubicin‐induced cardiotoxicity in juvenile mice.FEBS Lett.2021595121681169510.1002/1873‑3468.1409133876420
    [Google Scholar]
  348. ZhangL. FanC. JiaoH.C. ZhangQ. JiangY.H. CuiJ. LiuY. JiangY.H. ZhangJ. YangM.Q. LiY. XueY.T. Calycosin alleviates doxorubicin-induced cardiotoxicity and pyroptosis by inhibiting NLRP3 inflammasome activation.Oxid. Med. Cell. Longev.2022202211510.1155/2022/173383435035656
    [Google Scholar]
  349. KabelA.M. SalamaS.A. AdwasA.A. EstfanousR.S. Targeting oxidative stress, NLRP3 inflammasome, and autophagy by fraxetin to combat doxorubicin-induced cardiotoxicity.Pharmaceuticals.20211411118810.3390/ph1411118834832970
    [Google Scholar]
  350. ShamoonL. Espitia-CorredorJ.A. DongilP. Menéndez-RibesM. RomeroA. ValenciaI. Díaz-ArayaG. Sánchez-FerrerC.F. PeiróC. Resolvin E1 attenuates doxorubicin-induced endothelial senescence by modulating NLRP3 inflammasome activation.Biochem. Pharmacol.202220111507810.1016/j.bcp.2022.11507835551917
    [Google Scholar]
  351. ZhangE. ShangC. MaM. ZhangX. LiuY. SongS. LiX. Polyguluronic acid alleviates doxorubicin-induced cardiotoxicity by suppressing Peli1-NLRP3 inflammasome-mediated pyroptosis.Carbohydr. Polym.202332112133410.1016/j.carbpol.2023.12133437739547
    [Google Scholar]
  352. WanY. HeB. ZhuD. WangL. HuangR. ZhuJ. WangC. GaoF. Nicotinamide mononucleotide attenuates doxorubicin-induced cardiotoxicity by reducing oxidative stress, inflammation and apoptosis in rats.Arch. Biochem. Biophys.202171210905010.1016/j.abb.2021.10905034610336
    [Google Scholar]
  353. ChenX. TianC. ZhangZ. QinY. MengR. DaiX. ZhongY. WeiX. ZhangJ. ShenC. AstragalosideI.V. Astragaloside IV inhibits NLRP3 inflammasome-mediated pyroptosis via activation of Nrf2/HO-1 signaling pathway and protects against doxorubicin-induced cardiac dysfunction.Front. Biosci. 20232834510.31083/j.fbl280304537005753
    [Google Scholar]
  354. ChenH. ZhuJ. LeY. PanJ. LiuY. LiuZ. WangC. DouX. LuD. Salidroside inhibits doxorubicin-induced cardiomyopathy by modulating a ferroptosis-dependent pathway.Phytomedicine202299153964https://www.sciencedirect.com/science/article/pii/S094471132200042310.1016/j.phymed.2022.15396435180677
    [Google Scholar]
  355. WangY. YingX. WangY. ZouZ. YuanA. XiaoZ. GengN. QiaoZ. LiW. LuX. PuJ. Hydrogen sulfide alleviates mitochondrial damage and ferroptosis by regulating OPA3–NFS1 axis in doxorubicin-induced cardiotoxicity.Cell. Signal.2023107110655https://www.sciencedirect.com/science/article/pii/S089865682300069410.1016/j.cellsig.2023.11065536924813
    [Google Scholar]
  356. ZhangG. YuanC. SuX. ZhangJ. GokulnathP. VulugundamG. LiG. YangX. AnN. LiuC. SunW. ChenH. WuM. SunS. XingY. Relevance of ferroptosis to cardiotoxicity caused by anthracyclines: Mechanisms to target treatments.Front. Cardiovasc. Med.20229896792https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9234116/10.3389/fcvm.2022.89679235770215
    [Google Scholar]
  357. WangY. HanJ. ZhanS. GuoC. YinS. ZhanL. ZhouQ. LiuR. YanH. WangX. YanD. Fucoidan alleviates doxorubicin-induced cardiotoxicity by inhibiting ferroptosis via Nrf2/GPX4 pathway.Int. J. Biol. Macromol.2024276Pt 1133792https://www.sciencedirect.com/science/article/pii/S014181302404597510.1016/j.ijbiomac.2024.13379238992539
    [Google Scholar]
  358. LiaoH.H. DingW. ZhangN. ZhouZ.Y. LingZ. LiW.J. ChenS. TangQ.Z. Activation of AMPKα2 attenuated doxorubicin-induced cardiotoxicity via inhibiting lipid peroxidation associated ferroptosis.Free Radic. Biol. Med.2023205275290https://www.sciencedirect.com/science/article/pii/S089158492300486010.1016/j.freeradbiomed.2023.06.00437331642
    [Google Scholar]
  359. ZhangM. WuX. WenY. LiZ. ChenF. ZouY. DongX. LiuX. WangJ. Epirubicin induces cardiotoxicity through disrupting ATP6V0A2-dependent lysosomal acidification and triggering ferroptosis in cardiomyocytes.Cell Death Discov.2024101337https://www.nature.com/articles/s41420-024-02095-z10.1038/s41420‑024‑02095‑z39048556
    [Google Scholar]
  360. TaiP. ChenX. JiaG. ChenG. GongL. ChengY. LiZ. WangH. ChenA. ZhangG. ZhuY. XiaoM. WangZ. LiuY. ShanD. HeD. LiM. ZhanT. KhanA. LiX. ZengX. LiC. OuyangD. AiK. ChenX. LiuD. LiuZ. WeiD. CaoK. WGX50 mitigates doxorubicin-induced cardiotoxicity through inhibition of mitochondrial ROS and ferroptosis.J. Transl. Med.202321182310.1186/s12967‑023‑04715‑137978379
    [Google Scholar]
  361. FangX. WangH. HanD. XieE. YangX. WeiJ. GuS. GaoF. ZhuN. YinX. ChengQ. ZhangP. DaiW. ChenJ. YangF. YangH.T. LinkermannA. GuW. MinJ. WangF. Ferroptosis as a target for protection against cardiomyopathy.Proc. Natl. Acad. Sci. USA2019116726722680https://www.pnas.org/doi/full/10.1073/pnas.182102211610.1073/pnas.182102211630692261
    [Google Scholar]
  362. HannaM. SeddiekH. AboulhodaB.E. MorcosG.N.B. AkabawyA.M.A. ElbasetM.A. IbrahimA.A. KhalifaM.M. KhalifahI.M. FadelM.S. ShoukryT. Synergistic cardioprotective effects of melatonin and deferoxamine through the improvement of ferritinophagy in doxorubicin-induced acute cardiotoxicity.Front. Physiol.2022131050598https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2022.1050598/full10.3389/fphys.2022.105059836531171
    [Google Scholar]
  363. KitakataH. EndoJ. MatsushimaH. YamamotoS. IkuraH. HiraiA. KohS. IchiharaG. HiraideT. MoriyamaH. ShirakawaK. GotoS. KatsumataY. AnzaiA. KataokaM. TokuyamaT. IshidoS. YanagiS. FukudaK. SanoM. MITOL/MARCH5 determines the susceptibility of cardiomyocytes to doxorubicin-induced ferroptosis by regulating GSH homeostasis.J. Mol. Cell. Cardiol.2021161116129https://www.sciencedirect.com/science/article/pii/S002228282100159010.1016/j.yjmcc.2021.08.00634390730
    [Google Scholar]
  364. HeY. XiJ. FangJ. ZhangB. CaiW. Aloe-emodin alleviates doxorubicin-induced cardiotoxicity via inhibition of ferroptosis.Free Radic. Biol. Med.20232061321https://www.sciencedirect.com/science/article/pii/S089158492300512910.1016/j.freeradbiomed.2023.06.02537364691
    [Google Scholar]
  365. ChenT. QinY. LiY. LiY. LuoJ. FanL. FengM. WangZ. ZhaoY. Chiral polymer micelles alleviate adriamycin cardiotoxicity via iron chelation and ferroptosis inhibition.Adv. Funct. Mater.202333302300689https://onlinelibrary.wiley.com/doi/abs/10.1002/adfm.202300689[Internet].10.1002/adfm.202300689
    [Google Scholar]
  366. TadokoroT. IkedaM. AbeK. IdeT. MiyamotoH.D. FurusawaS. IshimaruK. WatanabeM. IshikitaA. MatsushimaS. KoumuraT. YamadaK. ImaiH. TsutsuiH. Ethoxyquin is a competent radical-trapping antioxidant for preventing ferroptosis in doxorubicin cardiotoxicity.J. Cardiovasc. Pharmacol.2022805690699https://journals.lww.com/cardiovascularpharm/abstract/2022/11000/ethoxyquin_is_a_competent_radical_trapping.9.aspx10.1097/FJC.000000000000132835881422
    [Google Scholar]
  367. ChenL. SunX. WangZ. ChenM. HeY. ZhangH. HanD. ZhengL. Resveratrol protects against doxorubicin-induced cardiotoxicity by attenuating ferroptosis through modulating the MAPK signaling pathway.Toxicol. Appl. Pharmacol.2024482116794https://www.sciencedirect.com/science/article/pii/S0041008X2300433710.1016/j.taap.2023.11679438142782
    [Google Scholar]
  368. ZhangH. WangZ. LiuZ. DuK. LuX. Protective effects of dexazoxane on rat ferroptosis in doxorubicin-induced cardiomyopathy through regulating HMGB1.Front. Cardiovasc. Med.20218685434https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2021.685434/full10.3389/fcvm.2021.68543434336950
    [Google Scholar]
  369. CuriglianoG. LenihanD. FradleyM. GanatraS. BaracA. BlaesA. HerrmannJ. PorterC. LyonA.R. LancellottiP. PatelA. DeCaraJ. MitchellJ. HarrisonE. MoslehiJ. WittelesR. CalabroM.G. OrecchiaR. de AzambujaE. ZamoranoJ.L. KroneR. IakobishviliZ. CarverJ. ArmenianS. KyB. CardinaleD. CipollaC.M. DentS. JordanK. ESMO Guidelines Committee. Electronic address: Clinicalguidelines@esmo.org Management of cardiac disease in cancer patients throughout oncological treatment: ESMO consensus recommendations.Ann. Oncol.202031217119010.1016/j.annonc.2019.10.02331959335
    [Google Scholar]
  370. CardinaleD. ColomboA. BacchianiG. TedeschiI. MeroniC.A. VegliaF. CivelliM. LamantiaG. ColomboN. CuriglianoG. FiorentiniC. CipollaC.M. Early detection of anthracycline cardiotoxicity and improvement with heart failure therapy.Circulation2015131221981198810.1161/CIRCULATIONAHA.114.01377725948538
    [Google Scholar]
  371. VejpongsaP. YehE.T.H. Prevention of anthracycline-induced cardiotoxicity: Challenges and opportunities.J. Am. Coll. Cardiol.201464993894510.1016/j.jacc.2014.06.116725169180
    [Google Scholar]
  372. DengS. YanT. JendrnyC. NemecekA. VinceticM. Gödtel-ArmbrustU. WojnowskiL. Dexrazoxane may prevent doxorubicin-induced DNA damage via depleting both Topoisomerase II isoforms.BMC Cancer201414184210.1186/1471‑2407‑14‑84225406834
    [Google Scholar]
  373. YuX. RuanY. ShenT. QiuQ. YanM. SunS. DouL. HuangX. WangQ. ZhangX. ManY. TangW. JinZ. LiJ. Dexrazoxane protects cardiomyocytes from doxorubicin-induced apoptosis by modulating miR-17-5p.BioMed Res. Int.2020202011110.1155/2020/510719332190669
    [Google Scholar]
  374. YuX. RuanY. HuangX. DouL. LanM. CuiJ. ChenB. GongH. WangQ. YanM. SunS. QiuQ. ZhangX. ManY. TangW. LiJ. ShenT. Dexrazoxane ameliorates doxorubicin-induced cardiotoxicity by inhibiting both apoptosis and necroptosis in cardiomyocytes.Biochem. Biophys. Res. Commun.2020523114014610.1016/j.bbrc.2019.12.02731837803
    [Google Scholar]
  375. LiJ. ChangH.M. BanchsJ. AraujoD.M. HassanS.A. WagarE.A. YehE.T.H. MengQ.H. Detection of subclinical cardiotoxicity in sarcoma patients receiving continuous doxorubicin infusion or pre-treatment with dexrazoxane before bolus doxorubicin.Cardiooncology202061110.1186/s40959‑019‑0056‑332154027
    [Google Scholar]
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  • Article Type:
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Keyword(s): apoptosis; cardiomyocytes; Cardiotoxicity; doxorubicin; inflammation; oxidative stress
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