Effect of different oral doses of isoniazid-rifampicin in rats

Mol Cell Biochem. 2006 Sep;289(1-2):39-47. doi: 10.1007/s11010-006-9145-3. Epub 2006 Apr 1.

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.

MeSH terms

  • Administration, Oral
  • Alanine Transaminase / blood
  • Alkaline Phosphatase / blood
  • Animals
  • Aspartate Aminotransferases / blood
  • Bilirubin / blood
  • Body Weight / drug effects
  • Isoniazid / administration & dosage*
  • Isoniazid / pharmacology*
  • Liver / drug effects*
  • Liver / pathology*
  • Male
  • Rats
  • Rats, Wistar
  • Rifampin / administration & dosage*
  • Rifampin / pharmacology*

Substances

  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Alkaline Phosphatase
  • Bilirubin
  • Isoniazid
  • Rifampin