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Hepatoprotective Effects of the Shark Bile Salt 5{beta}-Scymnol on Acetaminophen-Induced Liver Damage in Mice
Authors:MACRIDES, THEODORE   NAYLOR, LEE M.   KALAFATIS, NICOLETTE   SHIHATA, AMAL   WRIGHT, PAUL F. A.
Affiliation:*Biochemistry Unit, Department of Medical Laboratory Science G.P.O. Box 2476V, Melbourne, Victoria, 3001, Australia "{dagger}"Key Centre for Applied and Nutritional Toxicology, RMIT-University G.P.O. Box 2476V, Melbourne, Victoria, 3001, Australia

Received September 21, 1995; accepted April 15, 1996

Abstract:The hepatoprotective effect of the shark bile salt 5ß-Scymnolhas been studied in the model of acute hepatotoxicity inducedby administration of acetaminophen (APAP, paracetamol). 5ß-Scymnolat doses of 20, 35, and 70 mg/kg intraperitoneally (ip) decreasedsignificantly the serum activity of alanine aminotransferase,sorbitol dehydrogenase, and lactate dehydrogenase (p < 0.05)caused by APAP treatment (350 mg/kg ip) alone. The highest doseof 5ß-Scymnol remained hepatoprotective when administered4 hr after the APAP overdose. N-Acetylcysteine (NAC) is protectiveagainst APAP-induced hepatotoxicity at 250 and 500 mg/kg (ip)when administered up to 3 hr after APAP overdose, as shown bya significant reduction in serum enzyme activity. Coadministrationof 5ß-Scymnol (70 mg/kg) and NAC (250 mg/kg) alsoreduced serum enzyme levels and histopathological effects; however,a similar level of hepatoprotection was conferred by 5ß-Scymnoltreatment alone. In addition, 5ß-scymnol has potenthydroxyl radical quenching activity as it markedly inhibiteddeoxyribose degradation in a ferrous/ascorbate Fenton reactionsystem. These results indicate a possible role for the use of5ß-scymnol, either alone or concomitant with NAC,in the prevention of hepatic necrosis following toxic dosesof APAP.
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