The protective effect of taurine against cyclosporine A-induced oxidative stress and hepatotoxicity in rats.
Cyclosporine A (CsA) is the immunosuppressor which is most frequently used in transplant surgery and in the treatment of autoimmune diseases. Oxidative stress has been implicated as one of the possible mechanisms of CsA-induced hepatotoxicity. The present investigation examined the ability of taurine as an antioxidant to protect against CsA-induced oxidative stress and hepatotoxicity. CsA hepatotoxicity was induced by subcutaneous injection of CsA at a dose of 20mg/kg body weight daily for 21 days. Hepatotoxicity was assessed by reduced serum total protein level and increased serum levels of gamma glutamyl transferase (GGT), alanine aminotransferase (ALT), and aspartate aminotransaminase (AST). CsA treatment increased lipid peroxidation measured as thiobarbituric acid reactive substances (TBARS) concentration and decreased reduced glutathione (GSH) content and activities of catalase and glutathione peroxidase (GSH-Px) in the rat liver. Taurine administration (1% in the drinking water) for 3 days before and concurrently during CsA injections improved liver functions, as indicated by decline of serum transaminases and GGT levels and elevation of serum total protein. Moreover, taurine significantly reduced hepatic TBARS and increased GSH content and catalase and GSH-Px activities in the hepatic tissue. These results indicate that taurine has a protective action against CsA hepatotoxicity and suggest that taurine may find clinical application against a variety of toxins where cellular damage is a consequence of reactive oxygen species.
Hagar
Hanan H
HH
Department of Pharmacology, College of Medicine and KHUH, King Saud University, P.O. Box 2925, Riyadh 11461, Saudi Arabia. hananhhagar@yahoo.com
D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use*; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D016572:Cyclosporine / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000633:toxicity*; D004336:Drug Antagonism; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000633:toxicity*; D007279:Injections, Subcutaneous; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013654:Taurine / Q000008:administration & dosage / Q000627:therapeutic use*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014881:Water Supply
D000975:Antioxidants; D007166:Immunosuppressive Agents; D017392:Thiobarbituric Acid Reactive Substances; D013654:Taurine; D016572:Cyclosporine