Skip to main content
SpringerLink
Log in

Effect of Different Oral Doses of Isoniazid-Rifampicin in Rats

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Hepatotoxicity is one of the most serious adverse effects of antituberculosis drugs. The aim of this study was to produce a rat model of isoniazid-rifampicin (INH-RIF) induced hepatotoxicity. Materials and Methods: Wistar rats (100–150 g) were treated with different doses of INH i.e. 25, 50 and 75 mg/kg/day with a fixed dose of RIF i.e. 50 mg/kg/day intragastrically for a period of 28 days. Serum glutamate oxaloacetate aminotransferase (SGOT), glutamate pyruvate aminotransferase (SGPT), bilirubin (Bil) and alkaline phosphatase (ALP) were estimated at 0,14, 21 and 28 days in rats. Histological analysis was carried out to assess the liver. Results: Treatment of rats with INH–RIF (50 mg/kg/day each) induced hepatotoxicity as judged by elevated serum SGPT, SGOT, Bil and ALP as compared with their base line. Histological evaluation of INH–RIF induced hepatotoxicity also showed liver damage. Conclusion: The present study suggests that 50 mg/kg/day each of INH–RIF was selected as hepatotoxic dose (i.e. minimum dose with maximum hepatotoxicity) in wistar rats.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Sahbazian B, Weis SE: Treatment of active tuberculosis: Challenges and prospects. Clin Chest Med 26: 273–282, 2005

    Article  PubMed  Google Scholar 

  2. Fernandez-Villar A, Sopena B, Fernandez-Villar J, Vazquez-Gallardo R, Ulloa F, Leiro V, Mosteiro M, Pineiro L: The influence of risk factors on the severity of anti-tuberculosis drug-induced hepatotoxicity. Int J Tuberc Lung Dis 8: 1499–1505, 2004

    PubMed  CAS  Google Scholar 

  3. Hussawi Z, Kar P, Husain SA: Antituberculosis drug induced hepatitis: Risk factors, prevention and management. Indian J of Exp Biol 41: 1226–1232, 2003

    Google Scholar 

  4. Quenelle DC, Staas JK, Winchester GAA, Barrow ELW, Barrow WW: Efficacy of microencapsulated rifampicin in mycobacterium tuberculosis infected Mice. Antimicrob Agent Chemo 43: 1144–1115, 1999

    CAS  Google Scholar 

  5. Quenelle DC, Winchester GA, Staas JK, Barrlow LW: Treatment of tuberculosis using a combination of sustained released rifampicin loaded microspheres and oral dosing with isoniazid. Ant Agent and Chemo 45: 1637–1644, 2001

    Article  CAS  Google Scholar 

  6. Skakun NP, Slivka IuI: Effectiveness of tocopherol and anti-hypoxic agents in liver damage caused by antitubercular agents. Probl Tuberk 3: 57–59, 1991

    PubMed  Google Scholar 

  7. Reitman J, Franketl SA: Colorimetric method for the determination of serum glutamic oxaloacetic acid and serum glutamic pyruvic transaminase. Am J Clin Path 28: 56–63, 1957

    PubMed  CAS  Google Scholar 

  8. Powell WN: Serum biluribin estimation. Am J Clin Path 14: 55–57, 1944

    Google Scholar 

  9. Bergemer MKC: Method of enzymatic analysis. Academic press, New York 40: 783–785, 1963.

    Google Scholar 

  10. Brown JS, Wilson WE, Grant LD: Dosimetric comparisons of particle deposition and retention in rats and humans. Inhal Toxicol 17: 355–385, 2005

    PubMed  CAS  Google Scholar 

  11. Hardistiy JF, Brix AE: Comparative hepatic toxicity: Pre chronic liver toxicity in rodents. Toxicol Pathol 33: 35–40,2005

    Article  PubMed  CAS  Google Scholar 

  12. Frank I, Lahav D, Aroch I: Myocardial necrosis and severe metabolic acidosis associated with isoniazid poisoning in dog. Vet Reco 151: 638–639, 2002

    CAS  Google Scholar 

  13. Attri S, Rana SV, Vaiphei K, Sodi CP, Katyal R, Goel RC, Nain CK, Singh K: Isoniazid—rifampicin induced oxidative hepatic injury protection by N—acetylcysteine. Human & Exp Toxico 19: 517–522, 2000

    Article  CAS  Google Scholar 

  14. Kasilo OJ, Nihach CFB, Nahlet M: Isoniazid—International programme on chemical toxicity. Poisons information monograph . Pharmaceutical: 288–291, 1999

  15. Cro HJ, Mood BM, Magarey J: Rifampicin IARC Summary and Evaluation: 24–26, 1980

  16. Rifandin (Hoechst Marian Roussel) In: PDR Phsycian desk reference. 54th ed 2000 oradell. N J Medical Economics Data: 1379–1382, 2000

  17. Ellenhorn MJ, BarCeloux DG: Antiinfective drugs. Medical Toxicology, Diagnosis and Treatment of Human poisioning. Amsterdam Elsevier: 29, 1988

  18. Mandel GL, Sande MA: Antimicrobial agents. Goodman and Gillman. The pharmacologic basis of therapeutics. 7th ed. Macmillian Publish Co: 61–64, 1985

  19. Mitchell JR, Zimmerman HJ, Ishak KG: Thorgierson, U.P. Isoniazid liver injury: Clinical spectrum pathology and probable pathogenesis. Ann Intern Med 84: 181–192, 1976

    PubMed  CAS  Google Scholar 

  20. Karthikryan S: Hepatotoxicity of isoniazid: A study in the activity of marker enzymes of liver toxicity in serum and liver of rabbits. Ind J Pharmaco 36:247–249, 1995

    Google Scholar 

  21. Snodgross W, Potter W, Timbrell JA, Jollow DI: Possible mechanism of isoniazid related hepatic injury. Clin Res 22: 323–326, 1974

    Google Scholar 

  22. Heiserg GB, Hughes WC, Long CM: Rozmaiorkherh. The guinea pigs as model for isoniazid induced reactions. LabAnimal Sci 30: 42–50, 1980

    Google Scholar 

  23. Tasduq SA, Kaiser P, Gupta PK, Kapahi BK: Protective effect of 50% hydroalcoholic fruit extract of Emblica officinalis against antituberculosis drugs induced liver toxicity. Phytother Res 19: 193–197, 2005

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

    Satya V Rana, Ravinder Pal & Kartar Singh

  2. Department of Pathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

    Kim Vaiphie

  3. House No. 137, Sector 15-A, 160012, Chandigarh, India

    Satya V Rana

Authors
  1. Satya V Rana
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ravinder Pal
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kim Vaiphie
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kartar Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Satya V Rana.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rana, S.V., Pal, R., Vaiphie, K. et al. Effect of Different Oral Doses of Isoniazid-Rifampicin in Rats. Mol Cell Biochem 289, 39–47 (2006). https://doi.org/10.1007/s11010-006-9145-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-006-9145-3

Keywords

Search

Navigation