Skip to content
2000
Volume 25, Issue 9
  • ISSN: 1568-0266
  • E-ISSN: 1873-4294

Abstract

Background

Drug-induced hepatotoxicity is a major concern and is caused by all classes of medications, indicating a key area of research. Antitubercular drugs have a beneficial effect but cause hepatotoxicity on prolonged use.

Aim

The present work aimed to investigate the role of rifampicin-induced hepatic damage and the effect of Cliv-92 on rifampicin-induced alteration in rats.

Methods

Rats were administered with rifampicin, Cliv-92, and silymarin (standard) orally in 0.5% carboxymethyl cellulose (CMC) suspension, in doses of 100 mg/kg, once daily for fourteen days, one hour before the administration of rifampicin. Control animals were treated with 0.5% CMC. On the 14th day, 1hr after the last drug administration, tissue was collected, homogenized, and various parameters, viz. SOD, CAT, GPX, and cytochromes, were estimated from rat liver supernatant and compared with the control group. Blood serum parameters were also measured. Simultaneously, antioxidant activity and studies were performed. The constituent isoforms of Cliv-92 and silymarin and their metabolites were analyzed for different pharmacokinetic characteristics. Silymarin was used as a standard drug.

Results

The result of the study suggests that the hepatoprotective potential of Cliv-92 is due to its antioxidant property and inhibitory effect on hepatoproteins, cytochromes (CPY450). An finding validates the safety profile of Cliv-92, its metabolites, and the standard drug silymarin and also explains that the drug is non-mutagenic.

Conclusion

The result of this study indicated that both Cliv-92 and silymarin could be used to avoid drug-induced overload and hepatic damage.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/ctmc/10.2174/0115680266329609241223114551
2025-04-01
2025-10-30

  • From This Site

    /content/journals/ctmc/10.2174/0115680266329609241223114551
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. PanditA. SachdevaT. BafnaP. Drug-induced hepatotoxicity: A review.J. Appl. Pharm. Sci.201225233243
     [Google Scholar]
  2. BjörnssonE.S. BergmannO.M. BjörnssonH.K. KvaranR.B. OlafssonS. Incidence, presentation, and outcomes in patients with drug-induced liver injury in the general population of Iceland.Gastroenterology2013144714191425.e310.1053/j.gastro.2013.02.006
     [Google Scholar]
  3. BiourM. BenC.S. ChazouillèresO. GrangéJ. SerfatyL. PouponR. Drug-induced liver injury; fourteenth updated edition of the bibliographic database of liver injuries and related drugs.Gastroenterol. Clin. Biol.2004288-972075910.1016/s0399‑8320(04)95062‑2
     [Google Scholar]
  4. PorcedduM. BuronN. RousselC. LabbeG. FromentyB. Borgne-SanchezA. Prediction of liver injury induced by chemicals in human with a multiparametric assay on isolated mouse liver mitochondria.Toxicol. Sci.2012129233234510.1093/toxsci/KFS19722987451
     [Google Scholar]
  5. UpadhyayG. KumarA. SinghM.P. Effect of silymarin on pyrogallol- and rifampicin-induced hepatotoxicity in mouse.Eur. J. Pharmacol.20075651-319020110.1016/j.ejphar.2007.03.00417434476
     [Google Scholar]
  6. UpadhyayG. SinghA.K. KumarA. PrakashO. SinghM.P. Resveratrol modulates pyrogallol-induced changes in hepatic toxicity markers, xenobiotic metabolizing enzymes and oxidative stress.Eur. J. Pharmacol.20085961-314615210.1016/j.ejphar.2008.08.01918789925
     [Google Scholar]
  7. RanaS.V. AttriS. VaipheiK. PalR. AttriA. SinghK. Role of N-acetylcysteine in rifampicin-induced hepatic injury of young rats.World J. Gastroenterol.200612228729110.3748/wjg.v12.i2.28716482631
     [Google Scholar]
  8. ChowdhuryA. SantraA. BhattacharjeeK. GhatakS. SahaD.R. DhaliG.K. Mitochondrial oxidative stress and permeability transition in Isoniazid and Rifampicin induced liver injury in mice.J. Hepatol.200645111712610.1016/j.jhep.2006.01.02716545483
     [Google Scholar]
  9. GuptaY.K. SharmaM. ChaudharyG. Pyrogallol-induced hepatotoxicity in rats: A model to evaluate antioxidant hepatoprotective agents.Methods Find. Exp. Clin. Pharmacol.200224849750010.1358/mf.2002.24.8.70507012500429
     [Google Scholar]
  10. TasduqS. PeerzadaK. KoulS. BhatR. JohriR. Biochemical manifestations of anti-tuberculosis drugs induced hepatotoxicity and the effect of silymarin.Hepatol. Res.200531313213510.1016/j.hepres.2005.01.00515777701
     [Google Scholar]
  11. AhmedS. SultanaM. HasanM.M.U. AzharI. Analgesic and antiemetic activity of Cleome viscosa L.Pak. J. Bot.201143Special issue119122
     [Google Scholar]
  12. ChatterjeeA. PakrashiS.C. The Treatise on Indian Medicinal PlantsPublications & Information DirectorateNew Delhi1991
     [Google Scholar]
  13. TandonS. ChatterjeeA. ChattopadhyayS.K. KaurR. GuptaA.K. Pilot scale processing technology for extraction of Cliv-92: A combination of three coumarinolignoids cleomiscosins A, B and C from Cleome viscosa.Ind. Crops Prod.201031233534310.1016/j.indcrop.2009.11.014
     [Google Scholar]
  14. YadavN.P. ChattopadhyayS.K. PalA. ChandaD. GuptaA.K. Hepatoprotective effects and safety evaluation of coumarinolignoids isolated from Cleome viscosa seeds.Indian J. Pharm. Sci.201072675976510.4103/0250‑474X.8458921969749
     [Google Scholar]
  15. BawankuleD.U. ChattopadhyayS.K. PalA. SaxenaK. YadavS. YadavN.P. ManiD. TripathiA.K. BegS.U. SrivastavaA. GuptaA.K. KhanujaS.P.S. An in-vivo study of the immunomodulatory activity of coumarinolignoids from Cleome viscosa.Nat. Prod. Commun.20072910.1177/1934578X0700200911
     [Google Scholar]
  16. BondetV. Brand-WilliamsW. BersetC. Kinetics and mechanisms of antioxidant activity using the DPPH. free radical method.Lebensm. Wiss. Technol.199730660961510.1006/fstl.1997.0240
     [Google Scholar]
  17. MarcocciL. MaguireJ.J. DroylefaixM.T. PackerL. The nitric oxide-scavenging properties of Ginkgo biloba extract EGb 761.Biochem. Biophys. Res. Commun.1994201274875510.1006/bbrc.1994.17648003011
     [Google Scholar]
  18. BenzieI.F.F. StrainJ.J. The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: The FRAP assay.Anal. Biochem.19962391707610.1006/abio.1996.02928660627
     [Google Scholar]
  19. McDonaldS. PrenzlerP.D. AntolovichM. RobardsK. Phenolic content and antioxidant activity of olive extracts.Food Chem.2001731738410.1016/S0308‑8146(00)00288‑0
     [Google Scholar]
  20. PrietoP. PinedaM. AguilarM. Spectrophotometric quantitation of antioxidant capacity through the formation of a phosphomolybdenum complex: Specific application to the determination of vitamin E.Anal. Biochem.1999269233734110.1006/abio.1999.401910222007
     [Google Scholar]
  21. UbohF. OkonI.E. EkongM.B. Effect of aqueous extract of Psidium guajava leaves on liver enzymes, histological integrity and hematological indices in rats.Gastroenterol. Res.201031323810.4021/gr2010.02.174w27956982
     [Google Scholar]
  22. WheelerC.R. SalzmanJ.A. ElsayedN.M. OmayeS.T. KorteD.W. Automated assays for superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase activity.Anal. Biochem.1990184219319910.1016/0003‑2697(90)90668‑Y2327564
     [Google Scholar]
  23. MaierC.M. ChanP.H. Role of superoxide dismutases in oxidative damage and neurodegenerative disorders.Neuroscientist20028432333410.1177/10738584020080040812194501
     [Google Scholar]
  24. UrsiniF. MaiorinoM. GregolinC. The selenoenzyme phospholipid hydroperoxide glutathione peroxidase.Biochim. Biophys. Acta, Gen. Subj.19858391627010.1016/0304‑4165(85)90182‑53978121
     [Google Scholar]
  25. AlamS. KhanF. QSAR, docking, ADMET, and system pharmacology studies on tormentic acid derivatives for anticancer activity.J. Biomol. Struct. Dyn.20183692373239010.1080/07391102.2017.135584628705120
     [Google Scholar]
  26. AlamS. KhanF. Virtual screening, Docking, ADMET and System Pharmacology studies on Garcinia caged Xanthone derivatives for Anticancer activity.Sci. Rep.201881552410.1038/s41598‑018‑23768‑729615704
     [Google Scholar]
  27. AlamS. KhanF. 3D-QSAR studies on Maslinic acid analogs for Anticancer activity against Breast Cancer cell line MCF-7.Sci. Rep.201771601910.1038/s41598‑017‑06131‑028729623
     [Google Scholar]
  28. ChaturvediT. KumarA. KumarA. VermaR.S. PadaliaR.C. SundaresanV. ChauhanA. SaikiaD. SinghV.R. VenkateshaK.T. Chemical composition, genetic diversity, antibacterial, antifungal and antioxidant activities of camphor-basil (Ocimum kilimandscharicum Guerke).Ind. Crops Prod.201811824625810.1016/j.indcrop.2018.03.050
     [Google Scholar]
  29. MishraR. GuptaA.K. KumarA. LalR.K. SaikiaD. ChanotiyaC.S. Genetic diversity, essential oil composition, and in vitro antioxidant and antimicrobial activity of Curcuma longa L. germplasm collections.J. Appl. Res. Med. Aromat. Plants201810758410.1016/j.jarmap.2018.06.003
     [Google Scholar]
/content/journals/ctmc/10.2174/0115680266329609241223114551
Loading
In Vivo and In Silico Pharmacokinetics Studies on Coumarinolignoid Cliv-92: Unraveling its Effect on Rifampicin-Induced Hepatic Damage
Curr. Top. Med. Chem. 25, 1016 (2025); https://doi.org/10.2174/0115680266329609241223114551
/content/journals/ctmc/10.2174/0115680266329609241223114551
/content/journals/ctmc/10.2174/0115680266329609241223114551
Loading

Data & Media loading...


  • Article Type:     Research Article
Keyword(s): Coumarinolignoids; cytochrome P-450; glutathione; hepatoprotection; rifampicin

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test