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Volume 17, Issue 1
  • ISSN: 1874-4672
  • E-ISSN: 1874-4702
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Abstract

Background

Ischemia/reperfusion injury (IRI) is a leading cause of acute kidney injury (AKI) that induces inflammation and oxidative stress. The main goal of the current study was to assess the impact of fingolimod on kidney IRI in rats.

Methods

For this purpose, 18 male Wistar rats (220–250g) were divided into three groups including (i) Sham, (ii) I/R, and (iii) fingolimod+I/R. The last group was pretreated with a single dose of fingolimod (1mg/kg) (intraperitoneal injection) before induction of the I/R injury. Kidney function, oxidative stress marker (malondialdehyde), and antioxidant markers (catalase, superoxide dismutase, glutathione, glutathione peroxidase, and total antioxidant capacity) were determined in the kidney tissue of the rats. Moreover, kidney samples were taken for histological analysis.

Results

Fingolimod pre-treatment could significantly improve the glutathione peroxidase (p<0.01) and glutathione (p<0.001) activities along with the total antioxidant capacity levels (p<0.001) when compared to the I/R group. Moreover, significant recovery of kidney function and histology was seen in the fingolimod+ I/R group compared to the I/R group (p<0.01).

Conclusion

Fingolimod pretreatment could improve renal function, antioxidant capacity, and histological alterations after I/R injury. Hence, it might protect the kidney against IRI-related kidney damage including AKI and transplantation.

© 2024 The Author(s). Published by Bentham Science Publisher.
This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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2024-01-01
2024-11-26

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References

  1. YangT. ZhangX.M. TarnawskiL. PeleliM. ZhugeZ. TerrandoN. HarrisR.A. OlofssonP.S. LarssonE. PerssonA.E.G. LundbergJ.O. WeitzbergE. CarlstromM. Dietary nitrate attenuates renal ischemia-reperfusion injuries by modulation of immune responses and reduction of oxidative stress.Redox Biol.20171332033010.1016/j.redox.2017.06.00228623824
     [Google Scholar]
  2. KellyK.J. WilliamsW.W.Jr ColvinR.B. BonventreJ.V. Antibody to intercellular adhesion molecule 1 protects the kidney against ischemic injury.Proc. Natl. Acad. Sci.199491281281610.1073/pnas.91.2.8127904759
     [Google Scholar]
  3. YsebaertD.K. De GreefK.E. De BeufA. Van RompayA.R. VercauterenS. PersyV.P. De brOEM.E. T cells as mediators in renal ischemia/reperfusion injury.Kidney Int.200466249149610.1111/j.1523‑1755.2004.761_4.x15253695
     [Google Scholar]
  4. BurneM.J. DanielsF. El GhandourA. MauiyyediS. ColvinR.B. O’DonnellM.P. RabbH. Identification of the CD4+ T cell as a major pathogenic factor in ischemic acute renal failure.J. Clin. Invest.200110891283129010.1172/JCI20011208011696572
     [Google Scholar]
  5. SicaF. CentonzeD. ButtariF. Fingolimod immune effects beyond its sequestration ability.Neurol. Ther.20198223124010.1007/s40120‑019‑00162‑731696392
     [Google Scholar]
  6. KimuraT. HasegawaT. NakaiH. AzumaT. UsuiN. SasakiT. OkadaA. FTY720 reduces T-cell recruitment into murine intestinal allograft and prevents activation of graft-infiltrating cells.Transplantation20037591469147410.1097/01.TP.0000058816.13525.9212792499
     [Google Scholar]
  7. HwangM.W. MatsumoriA. FurukawaY. OnoK. OkadaM. IwasakiA. HaraM. SasayamaS. FTY720, a new immunosuppressant, promotes long-term graft survival and inhibits the progression of graft coronary artery disease in a murine model of cardiac transplantation.Circulation1999100121322132910.1161/01.CIR.100.12.132210491378
     [Google Scholar]
  8. SegoloniG.P. QuagliaM. New immunosuppressive drugs for prevention and treatment of rejection in renal transplant.J. Nephrol.200619557858617136684
     [Google Scholar]
  9. ZwackaR.M. ZhangY. HalldorsonJ. SchlossbergH. DudusL. EngelhardtJ.F. CD4(+) T-lymphocytes mediate ischemia/reperfusion-induced inflammatory responses in mouse liver.J. Clin. Invest.1997100227928910.1172/JCI1195339218504
     [Google Scholar]
  10. HlaT. LeeM.J. AncellinN. PaikJ.H. KlukM.J. Lysophospholipids--receptor revelations.Science200129455481875187810.1126/science.106532311729304
     [Google Scholar]
  11. SpiegelS. MilstienS. Sphingosine-1-phosphate: An enigmatic signalling lipid.Nat. Rev. Mol. Cell Biol.20034539740710.1038/nrm110312728273
     [Google Scholar]
  12. BrinkmannV. LynchK.R. FTY720: targeting G-protein-coupled receptors for sphingosine 1-phosphate in transplantation and autoimmunity.Curr. Opin. Immunol.200214556957510.1016/S0952‑7915(02)00374‑612183155
     [Google Scholar]
  13. MandalaS. HajduR. BergstromJ. QuackenbushE. XieJ. MilliganJ. ThorntonR. SheiG.J. CardD. KeohaneC. RosenbachM. HaleJ. LynchC.L. RupprechtK. ParsonsW. RosenH. Alteration of lymphocyte trafficking by sphingosine-1-phosphate receptor agonists.Science2002296556634634910.1126/science.107023811923495
     [Google Scholar]
  14. ShawB. DoolenS. IannittiT. DonahueR. TaylorB. (184) Fingolimod behaves as an agonist at sphingosine-1-phosphate receptor 1 to inhibit pain in an experimental autoimmune encephalomyelitis model of multiple sclerosis.J. Pain2017184S2210.1016/j.jpain.2017.02.091
     [Google Scholar]
  15. QianY. GaoC. ZhaoX. SongY. LuoH. AnS. HuangJ. ZhangJ. JiangR. Fingolimod attenuates lung injury and cardiac dysfunction after traumatic brain injury.J. Neurotrauma202037192131214010.1089/neu.2019.695132434456
     [Google Scholar]
  16. LiuG. BiY. WangR. YangH. ZhangY. WangX. LiuH. LuY. ZhangZ. ChenW. ChuY. YangR. Targeting S1P1 receptor protects against murine immunological hepatic injury through myeloid-derived suppressor cells.J. Immunol.201419273068307910.4049/jimmunol.130119324567529
     [Google Scholar]
  17. RungatscherA. LinardiD. NaseerA. ManiR. HoxhaS. LucianiG.B. FaggianG. Sphingosine-1-phosphate receptor agonist fingolimod reduces myocardial ischemia-reperfusion injury and apoptosis increasing long-term left ventricular function after heart transplantation.J. Heart Lung Transplant.2019384S22310.1016/j.healun.2019.01.546
     [Google Scholar]
  18. ZhangL. SuiR. ZhangL. Fingolimod protects against cerebral ischemia reperfusion injury in rats by reducing inflammatory cytokines and inhibiting the activation of p38 MAPK and NF-κB signaling pathways.Neurosci. Lett.202277113641310.1016/j.neulet.2021.13641334942319
     [Google Scholar]
  19. TroncosoP. OrtízM. MartínezL. KahanB.D. FTY 720 prevents ischemic reperfusion damage in rat kidneys.Transplant. Proc.2001331-285785910.1016/S0041‑1345(00)02349‑611267102
     [Google Scholar]
  20. ShiZ. LiT. KangD. SuH. TuF. Fingolimod attenuates renal ischemia/reperfusion-induced acute lung injury by inhibiting inflammation and apoptosis and modulating S1P metabolism.J. Int. Med. Res.202149810.1177/0300060521103280634340580
     [Google Scholar]
  21. MelnikovV.Y. FaubelS. SiegmundB. LuciaM.S. LjubanovicD. EdelsteinC.L. Neutrophil-independent mechanisms of caspase-1– and IL-18–mediated ischemic acute tubular necrosis in mice.J. Clin. Invest.200211081083109110.1172/JCI021562312393844
     [Google Scholar]
  22. ManK. NgK.T. LeeT.K. ChungM.L. SunC.K. XianL.L. ZhaoY. HoJ.W. SheungT.F. FTY720 attenuates hepatic ischemia-reperfusion injury in normal and cirrhotic livers.Am. J. Transplant.200551404910.1111/j.1600‑6143.2004.00642.x15636610
     [Google Scholar]
  23. BuddeK. SchützM. GlanderP. PetersH. WaiserJ. LiefeldtL. NeumayerH.H. BöhlerT. FTY720 (fingolimod) in renal transplantation.Clin. Transplant.200620s17Suppl. 17172410.1111/j.1399‑0012.2006.00596.x17100697
     [Google Scholar]
  24. MüllerH. HoferS. KaneiderN. NeuwirtH. MosheimerB. MayerG. KonwalinkaG. HeuflerC. TiefenthalerM. The immunomodulator FTY720 interferes with effector functions of human monocyte-derived dendritic cells.Eur. J. Immunol.200535253354510.1002/eji.20042555615657952
     [Google Scholar]
  25. YevgiR. DemirR. Oxidative stress activity of fingolimod in multiple sclerosis.Clin. Neurol. Neurosurg.202120210650010.1016/j.clineuro.2021.10650033508648
     [Google Scholar]
  26. Morales-RuizM. LeeM.J. ZöllnerS. GrattonJ.P. ScotlandR. ShiojimaI. WalshK. HlaT. SessaW.C. Sphingosine 1-phosphate activates Akt, nitric oxide production, and chemotaxis through a Gi protein/phosphoinositide 3-kinase pathway in endothelial cells.J. Biol. Chem.200127622196721967710.1074/jbc.M00999320011278592
     [Google Scholar]
  27. FerreroM.E. In Vivo vascular leakage assay.Tumor Necrosis Factor: Methods and Protocols. CortiA. GhezziP. Totowa, NJHumana Press200419119810.1385/1‑59259‑771‑8:191
     [Google Scholar]
  28. AwadA.S. YeH. HuangL. LiL. FossF.W.Jr MacdonaldT.L. LynchK.R. OkusaM.D. Selective sphingosine 1-phosphate 1 receptor activation reduces ischemia-reperfusion injury in mouse kidney.Am. J. Physiol. Renal Physiol.20062906F1516F152410.1152/ajprenal.00311.200516403835
     [Google Scholar]
  29. ThangadaS. ShapiroL.H. SilvaC. YamaseH. HlaT. FerrerF.A. Treatment with the immunomodulator FTY720 (fingolimod) significantly reduces renal inflammation in murine unilateral ureteral obstruction.J. Urol.20141915S1508151610.1016/j.juro.2013.10.07224679864
     [Google Scholar]
  30. HuangQ. LiangQ. ChenH. WangM. HuangQ. ZhengD. LinP. Protective effect of fingolimod on renal ischemia reperfusion injury model mice and its mechanism study.J China Pharmacy2018125457
     [Google Scholar]
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The Effect of Fingolimod on Renal Ischemia/Reperfusion Injury in a Rat Model
Curr Mol Pharmacol 17, e250823220363 (2024); https://doi.org/10.2174/1874467217666230825113406
/content/journals/cmp/10.2174/1874467217666230825113406
/content/journals/cmp/10.2174/1874467217666230825113406
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  • Article Type:     Research Article
Keyword(s): Acute kidney injury; Antioxidant; Fingolimod; Ischemia-reperfusion; Oxidative stress; S1P1-5

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