STUDY OF OXIDATIVE-STRESS IN ISONIAZID-RIFAMPICIN INDUCED HEPATIC-INJURY IN YOUNG-RATS

The role of oxidative-stress as a mechanism of hepatotoxicity caused b y combination of isoniazid (INH) and Rifampicin (RMP) was investigated in young growing rats. A successful model of hepatotoxicity was produ ced by giving 50 mg/kg/day each of INH and RMP in two weeks. Liver sho wed type II hepatocellular changes (microvesicular fat deposition) wit h mild portal triaditis. The glutathione and related thiols were signi ficantly decreased in both blood and fiver tissues with combination of INH and RMP treatment. Superoxide dismutase, glutathione peroxidase, catalase and glutathione-S-transferases with CDNB and DCNB as substrat es were decreased in the, combination treated group. Glutathione reduc tase, glutathione-S-transferase with ethacrynic acid as substrate and lipid peroxidation exhibited a significant increase with treatment. Th e altered profile of antioxidant enzymes with increased lipid peroxida tion indicated the enhanced oxidative-stress in combination of INH and RMP treatment. All the findings are faithfully reflected in the blood tissue except superoxide dismutase which showed significant enhanceme nt in this tissue. INH and RMP hepatotoxicity is thus appeared to be m ediated through oxidative-stress.