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Volume 21, Issue 17
  • ISSN: 1570-1808
  • E-ISSN: 1875-628X

Abstract

Background

Oxidative stress plays a key role in the development of a wide range of diseases, including diabetes and cancer. Recent studies reported that the derivatives of triazole compounds have a potent antioxidant activity. Therefore, this study was designed to investigate the hepatoprotective effect of a novel newly synthesized 5-mercapto-1,2,4-triazole based on nalidixic acid [1-ethyl-3-(5-mercapto-4-(-tolyl)-4-1,2,4-triazol-3-yl)-7-methyl-1,8-naphthyridin] (MTTN) 3 compound against CCl induced oxidative stress in mice.

Materials and Methods

The MTTN compound was synthesized through the interaction and then cyclization of p-tolylisothiocyanate with nalidixic acid hydrazide. By using 1H-NMR, 13C-NMR, IR, and elemental analyses, the structure of the newly synthesized MTTN compound was identified. To investigate the hepatoprotective effect of this compound, forty BALB/c mice were divided into four groups (n=10) as follows: the control group, the oxidative stress-induced group, which was intraperitoneally injected with 10% CCl (2 mL/kg), one pre-treatment group, which was treated orally with 200 mg/kg of MTTN compound for 8 days before being treated with CCl at day 8, and one post-treatment group, which was treated orally with 200 mg/kg of MTTN compound for 8 days simultaneously with CCl co-administration at days 3 and 5. At day 9, animals were scarified and serum and liver samples were collected.

Results

CCl administration caused significant hepatotoxicity as evidenced by marked elevation in the serum activity of the liver enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and high blood cholesterol levels. Furthermore, the hepatic malondialdehyde (MDA) level, a marker of lipid peroxidation, was increased with CCl administration that was associated with a decrease in the hepatic superoxide dismutase (SOD) and catalase (CAT) activities ( < 0.05). However, pre and post-treatment with the newly synthesized MTTN compound significantly reduced the serum levels of AST, ALT, and cholesterol and reduced hepatic oxidative stress as indicated by the decrease in the hepatic MDA level and the increases in the SOD and CAT activities ( < 0.05).

Conclusion

This study suggests that the newly synthesized MTTN compound has a potent antioxidant property and can protect against CCl-induced liver injury. Thus, with more clinical studies, this compound may be used as effective therapeutic agents against oxidative stress related diseases.

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2024-06-24
2025-06-27

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References

  1. OzcanA. OgunM. Biochemistry of reactive oxygen and nitrogen species; intechopen, 20153375810.5772/61193
     [Google Scholar]
  2. SiesH. Oxidative stress: Concept and some practical aspects.Antioxidants20209985210.3390/antiox9090852 32927924
     [Google Scholar]
  3. CheesemanK.H. Mechanisms and effects of lipid peroxidation.Mol. Aspects Med.199314319119710.1016/0098‑2997(93)90005‑X 8264333
     [Google Scholar]
  4. NandiA. Role of catalase in oxidative stress-and age-associated degenerative diseases.Oxid. Med. Cell. Longev.20192019961309010.1155/2019/9613090
     [Google Scholar]
  5. ShaikhM.H. SubhedarD.D. KhanF.A.K. SangshettiJ.N. ShingateB.B. 1,2,3-Triazole incorporated coumarin derivatives as potential antifungal and antioxidant agents.Chin. Chem. Lett.201627229530110.1016/j.cclet.2015.11.003
     [Google Scholar]
  6. KrystonT.B. GeorgievA.B. PissisP. GeorgakilasA.G. Role of oxidative stress and DNA damage in human carcinogenesis.Mutat. Res.20117111-219320110.1016/j.mrfmmm.2010.12.016 21216256
     [Google Scholar]
  7. LiuZ. RenZ. ZhangJ. ChuangC.C. KandaswamyE. ZhouT. ZuoL. Role of ROS and nutritional antioxidants in human diseases.Front. Physiol.2018947710.3389/fphys.2018.00477 29867535
     [Google Scholar]
  8. RosiniM. SimoniE. MilelliA. MinariniA. MelchiorreC. Oxidative stress in Alzheimer’s disease: Are we connecting the dots?J. Med. Chem.20145772821283110.1021/jm400970m 24131448
     [Google Scholar]
  9. SunF. HamagawaE. TsutsuiC. OnoY. OgiriY. KojoS. Evaluation of oxidative stress during apoptosis and necrosis caused by carbon tetrachloride in rat liver.Biochim. Biophys. Acta Mol. Basis Dis.20011535218619110.1016/S0925‑4439(00)00098‑3 11342007
     [Google Scholar]
  10. ManonmaniP. Hepatoprotective activity of aqueous extract of Phyllanthusniruri in CCl4 induced liver toxicity-in vivo study.Res. J. Biotechnol.20151091117
     [Google Scholar]
  11. Sotelo-FélixJ.I. Martinez-FongD. Muriel De la TorreP. Protective effect of carnosol on CCl4-induced acute liver damage in rats.Eur. J. Gastroenterol. Hepatol.20021491001100610.1097/00042737‑200209000‑00011 12352220
     [Google Scholar]
  12. AhmadS. Novel flurbiprofen clubbed oxadiazole derivatives as potential urease inhibitors and their molecular docking study.RSC Adv.20231337257172572810.1039/D3RA03841F
     [Google Scholar]
  13. RaniP. 1, 2, 3-Triazole and its applications in various fields.Int Refereed J. Rev. Res.20142623482001
     [Google Scholar]
  14. StrzeleckaM. ŚwiątekP. 1,2,4-triazoles as important antibacterial agents.Pharmaceuticals202114322410.3390/ph14030224 33799936
     [Google Scholar]
  15. UpmanyuN. KumarS. KharyaM.D. ShahK. MishraP. Synthesis and anti-microbial evaluation of some novel 1,2,4-triazole derivatives.Acta Pol. Pharm.2011682213221 21485294
     [Google Scholar]
  16. PeytonL.R. GallagherS. HashemzadehM. Triazole antifungals: A review.Drugs Today 2015511270571810.1358/dot.2015.51.12.2421058 26798851
     [Google Scholar]
  17. ZafarW. SumrraS.H. ChohanZ.H. A review: Pharmacological aspects of metal based 1,2,4-triazole derived Schiff bases.Eur. J. Med. Chem.202122211360210.1016/j.ejmech.2021.113602 34139626
     [Google Scholar]
  18. AbdelmotyS.G. HetaH.F. Synthesis of new 1, 2, 4-triazole derivatives of nalidixic acid as potential antibacterial and antifungal agents.Bullet. Pharmac. Sci.Assiut2009321125140
     [Google Scholar]
  19. BourguignonG.J. LevittM. SternglanzR. Studies on the mechanism of action of nalidixic acid.Antimicrob. Agents Chemother.19734447948610.1128/AAC.4.4.479 4208771
     [Google Scholar]
  20. CrumplinG.C. SmithJ.T. Nalidixic acid: an antibacterial paradox.Antimicrob. Agents Chemother.19758325126110.1128/AAC.8.3.251 1101818
     [Google Scholar]
  21. TohmaH. Gülçinİ. BursalE. GörenA.C. AlwaselS.H. KöksalE. Antioxidant activity and phenolic compounds of ginger (Zingiber officinale Rosc.) determined by HPLC-MS/MS.J. Food Meas. Charact.201711255656610.1007/s11694‑016‑9423‑z
     [Google Scholar]
  22. MichalakM. Plant-derived antioxidants: Significance in skin health and the ageing process.Int. J. Mol. Sci.2022232585
     [Google Scholar]
  23. BrunoM.R. Variability and chemical composition of the extractive content of woody residues from three European orchard species: apricot (Prunus Armeniaca L.), olive (Olea Europea L.), and orange trees (Citrus Sinensis L.).JSFA Rep.202332829710.1002/jsf2.99
     [Google Scholar]
  24. CeylanS. BayrakH. Basoglu OzdemirS. UygunY. MermerA. DemirbasN. UlkerS. Microwave-assisted and conventional synthesis of novel antimicrobial 1,2,4-triazole derivatives containing nalidixic acid skeleton.Heterocycl. Commun.201622422923710.1515/hc‑2016‑0019
     [Google Scholar]
  25. ShkoorM. TashtoushH. Al-TalibM. MhaidatI. Al-HiariY. KasabriV. AlalawiS. Synthesis and antiproliferative and antilipolytic activities of a series of 1,3- and 1,4-bis[5-(R-sulfanyl)-1,2,4-triazol-3-yl)benzenes.Russ. J. Org. Chem.20215771141115110.1134/S1070428021070149
     [Google Scholar]
  26. WedianF. A corrosion inhibitor for aluminum by novel synthesized triazole compounds in basic medium.Int J Corros Scale Inhib202211364381
     [Google Scholar]
  27. BuegeJ.A. AustS.D. Microsomal lipid peroxidation.Methods in enzymologyElsevier1978302310
     [Google Scholar]
  28. RiteshK.R. SuganyaA. DileepkumarH.V. RajashekarY. ShivanandappaT. A single acute hepatotoxic dose of CCl 4 causes oxidative stress in the rat brain.Toxicol. Rep.2015289189510.1016/j.toxrep.2015.05.012 28962426
     [Google Scholar]
  29. ValkoM. RhodesC.J. MoncolJ. IzakovicM. MazurM. Free radicals, metals and antioxidants in oxidative stress-induced cancer.Chem. Biol. Interact.2006160114010.1016/j.cbi.2005.12.009 16430879
     [Google Scholar]
  30. AhmadG. ChamiB. El KazziM. WangX. MoreiraM.T.S. HamiltonN. MawA.M. HamblyT.W. WittingP.K. Antioxidant activity.Antioxidants201989e202302338 31540488
     [Google Scholar]
  31. HalliwellB. Drug antioxidant effects. A basis for drug selection?Drugs199142456960510.2165/00003495‑199142040‑00003 1723362
     [Google Scholar]
  32. ChenS. GuoX. YuS. ZhouY. LiZ. SunY. Metabolic syndrome and serum liver enzymes in the general Chinese population.Int. J. Environ. Res. Public Health201613222310.3390/ijerph13020223 26901209
     [Google Scholar]
  33. SadeghiH. Hepatoprotective effect of Cichorium intybus on CCl4-induced liver damage in rats.Afr. J. Biochem. Res.200826141144
     [Google Scholar]
  34. KolodziejczykL. SiemieniukE. SkrzydlewskaE. Antioxidant potential of rat liver in experimental infection with Fasciola hepatica.Parasitol. Res.200596636737210.1007/s00436‑005‑1377‑8 15928904
     [Google Scholar]
  35. BollM. LutzW.D. BeckerE. StampflA. Mechanism of carbon tetrachloride-induced hepatotoxicity. Hepatocellular damage by reactive carbon tetrachloride metabolites.Z. Naturforsch. C J. Biosci.2001567-864965910.1515/znc‑2001‑7‑826 11531102
     [Google Scholar]
  36. BollM. WeberL.W.D. BeckerE. StampflA. Pathogenesis of carbon tetrachloride-induced hepatocyte injury bioactivation of CCI4 by cytochrome P450 and effects on lipid homeostasis.Z. Naturforsch. C J. Biosci.2001561-211112110.1515/znc‑2001‑1‑218 11302200
     [Google Scholar]
  37. Di PaolaR. ModafferiS. SiracusaR. CordaroM. D’AmicoR. OntarioM.L. InterdonatoL. SalinaroA.T. FuscoR. ImpellizzeriD. CalabreseV. CuzzocreaS. S-acetyl-glutathione attenuates carbon tetrachloride-induced liver injury by modulating oxidative imbalance and inflammation.Int. J. Mol. Sci.2022238442910.3390/ijms23084429 35457246
     [Google Scholar]
  38. PalR. MohantaP.K. BhutiaY. GhoshA. SherpaM.L. Serum malondialdehyde level: Surrogate stress marker in the Sikkimese diabetics.J. Nat. Sci. Biol. Med.20112110711210.4103/0976‑9668.82309 22470243
     [Google Scholar]
  39. MoselhyS.S. AliH.K.H. Hepatoprotective effect of Cinnamon extracts against carbon tetrachloride induced oxidative stress and liver injury in rats.Biol. Res.2009421939810.4067/S0716‑97602009000100009 19621136
     [Google Scholar]
  40. MaoG.D. ThomasP.D. LopaschukG.D. PoznanskyM.J. Superoxide dismutase (SOD)-catalase conjugates. Role of hydrogen peroxide and the Fenton reaction in SOD toxicity.J. Biol. Chem.1993268141642010.1016/S0021‑9258(18)54167‑3 8380162
     [Google Scholar]
  41. Al-MansuryS. AboktifaM.A. JassimA.M. BalakitA.A. AlkazazzF.F. Evaluation the antioxidant enzymes activity in adults male rats treated with some new 3-mercapto1,2,4-triazole derivatives.Res. J. Pharm. Technol.202215122422810.52711/0974‑360X.2022.00037
     [Google Scholar]
  42. MhaidatI. BanidomiS. WedianF. BadarnehR. TashtoushH. AlmomaniW. Al-MazaidehG.M. AlharbiN.S. ThiruvengadamM. Antioxidant and antibacterial activities of 5-mercapto(substitutedthio)-4-substituted-1,2,4-triazol based on nalidixic acid: A comprehensive study on its synthesis, characterization, and In silico evaluation.Heliyon2024107e2820410.1016/j.heliyon.2024.e28204 38571635
     [Google Scholar]
  43. ZykovaS. Antioxidant activity and acute toxicity of new n 4-substituted5-(1, 2, 4-triazole-1-ylmethyl)-1, 2, 4-triazole-3-thiones and s-derivatives.Int. J. Pharmac. Res.2021113
     [Google Scholar]
  44. ChenY. Synthesis and antioxidant activity of cationic 1,2,3-triazole functionalized starch derivatives.Polymers 2020121112
     [Google Scholar]
  45. UlrichK. JakobU. The role of thiols in antioxidant systems.Free Radic. Biol. Med.2019140142710.1016/j.freeradbiomed.2019.05.035 31201851
     [Google Scholar]
  46. de OliveiraJ. HortM.A. MoreiraE.L.G. GlaserV. Ribeiro-do-ValleR.M. PredigerR.D. FarinaM. LatiniA. de BemA.F. Positive correlation between elevated plasma cholesterol levels and cognitive impairments in LDL receptor knockout mice: relevance of cortico-cerebral mitochondrial dysfunction and oxidative stress.Neuroscience20111979910610.1016/j.neuroscience.2011.09.009 21945034
     [Google Scholar]
  47. MarimuthuS. AdluriR.S. RajagopalanR. MenonV.P. Protective role of ferulic acid on carbon tetrachloride-induced hyperlipidemia and histological alterations in experimental rats. jbcpp, 2013241596610.1515/jbcpp‑2012‑005323241587
     [Google Scholar]
  48. RajanS. PuriS. KumarD. BabuM.H. ShankarK. VarshneyS. SrivastavaA. GuptaA. ReddyM.S. GaikwadA.N. Novel indole and triazole based hybrid molecules exhibit potent anti-adipogenic and antidyslipidemic activity by activating Wnt3a/β-catenin pathway.Eur. J. Med. Chem.20181431345136010.1016/j.ejmech.2017.10.034 29153558
     [Google Scholar]
/content/journals/lddd/10.2174/0115701808294306240613104855
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The Hepatoprotective Effect of a Newly Synthesized 5-mercapto-1,2,4-triazole Derivative based on Nalidixic Acid against CCl4 induced Oxidative Stress in Mice
Letters in Drug Design & Discovery 21, 3823 (2024); https://doi.org/10.2174/0115701808294306240613104855
/content/journals/lddd/10.2174/0115701808294306240613104855
/content/journals/lddd/10.2174/0115701808294306240613104855
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  • Article Type:     Research Article
Keyword(s): CCl4; Liver; mice; nalidixic acid; oxidative stress; triazole derivative

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