Study of oxidative-stress in isoniazid-rifampicin induced hepatic injury in young rats.
The role of oxidative-stress as a mechanism of hepatotoxicity caused by combination of isoniazid (INH) and Rifampicin (RMP) was investigated in young growing rats. A successful model of hepatotoxicity was produced by giving 50 mg/kg/day each of INH and RMP in two weeks. Liver showed type II hepatocellular changes (microvesicular fat deposition) with mild portal triaditis. The glutathione and related thiols were significantly decreased in both blood and liver tissues with combination of INH and RMP treatment. Superoxide dismutase, glutathione peroxidase, catalase and glutathione-S-transferases with CDNB and DCNB as substrates were decreased in the combination treated group. Glutathione reductase, glutathione-S-transferase with ethacrynic acid as substrate and lipid peroxidation exhibited a significant increase with treatment. The altered profile of antioxidant enzymes with increased lipid peroxidation 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 enhancement in this tissue. INH and RMP hepatotoxicity is thus appeared to be mediated through oxidative-stress.
Sodhi
C P
CP
Department of Gastroenterology and Pathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Rana
S V
SV
Mehta
S K
SK
Vaiphei
K
K
Attari
S
S
Mehta
S
S
D000818:Animals; D000995:Antitubercular Agents / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury; D005978:Glutathione / Q000097:blood; D005979:Glutathione Peroxidase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D007538:Isoniazid / Q000633:toxicity*; D015227:Lipid Peroxidation; D008107:Liver Diseases / Q000378:metabolism / Q000473:pathology; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D012293:Rifampin / Q000633:toxicity*
D000995:Antitubercular Agents; D005979:Glutathione Peroxidase; D005982:Glutathione Transferase; D005978:Glutathione; D007538:Isoniazid; D012293:Rifampin