Isoniazid- and rifampicin-induced oxidative hepatic injury--protection by N-acetylcysteine.
The role of N-acetylcysteine (NAC), a glutathione (GSH) precursor, was investigated in protection against isoniazid- (INH) and rifampicin- (RIF) induced oxidative hepatic injury in young Wistar rats. The hepatotoxic dose of INH and RIF was 50 mg kg(-1) day(-1) each and the hepatoprotective dose of NAC was 100 mg kg(-1) day(-1). All drugs were administered intraperitoneally (i.p.) in sterile water (4.0 ml kg(-1) day(-1)) over a period of 3 weeks. Status of oxidative/antioxidative profiles was the mechanistic approach to assess the hepatotoxicity and/or hepatoprotection. The oxidative injury in INH-RIF co-exposed animals was closely associated with significant decline of GSH and related thiols, as well as with compromised antioxidant enzyme system. The oxidative stress was further supported by increased lipid peroxidation observed in these animals. The co-administration of NAC prevented the induction of oxidative stress in INH-RIF co-exposed animals. The amelioration of oxidative stress by NAC was faithfully reflected as normal morphology in these animals, except the presence of mild degree of portal triaditis in one animal co-exposed to INH-RIF and NAC. In contrast, the animals co-exposed to INH-RIF alone showed histological lesions which ranged from intralobular inflammation to patchy necrosis. These results suggest that INH-RIF-induced oxidative injury can be prevented by supporting the cellular antioxidant defense mechanism by NAC.
Attri
S
S
Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Rana
S V
SV
Vaiphei
K
K
Sodhi
C P
CP
Katyal
R
R
Goel
R C
RC
Nain
C K
CK
Singh
K
K
D000111:Acetylcysteine / Q000627:therapeutic use*; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D002374:Catalase / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004347:Drug Interactions; D007274:Injections, Intraperitoneal; D007538:Isoniazid / Q000008:administration & dosage / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D012293:Rifampin / Q000008:administration & dosage / Q000633:toxicity*; D013482:Superoxide Dismutase / Q000378:metabolism
D003577:Cytochrome P-450 Enzyme System; D002374:Catalase; D013482:Superoxide Dismutase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D007538:Isoniazid; D012293:Rifampin; D000111:Acetylcysteine