© 1996 Oxford University Press
research-article |
Hepatoprotective Effects of the Shark Bile Salt 5ß-Scymnol on Acetaminophen-Induced Liver Damage in Mice
*Biochemistry Unit, Department of Medical Laboratory Science G.P.O. Box 2476V, Melbourne, Victoria, 3001, Australia
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
The hepatoprotective effect of the shark bile salt 5ß-Scymnol has been studied in the model of acute hepatotoxicity induced by administration of acetaminophen (APAP, paracetamol). 5ß-Scymnol at doses of 20, 35, and 70 mg/kg intraperitoneally (ip) decreased significantly 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 dose of 5ß-Scymnol remained hepatoprotective when administered 4 hr after the APAP overdose. N-Acetylcysteine (NAC) is protective against APAP-induced hepatotoxicity at 250 and 500 mg/kg (ip) when administered up to 3 hr after APAP overdose, as shown by a significant reduction in serum enzyme activity. Coadministration of 5ß-Scymnol (70 mg/kg) and NAC (250 mg/kg) also reduced serum enzyme levels and histopathological effects; however, a similar level of hepatoprotection was conferred by 5ß-Scymnol treatment alone. In addition, 5ß-scymnol has potent hydroxyl radical quenching activity as it markedly inhibited deoxyribose degradation in a ferrous/ascorbate Fenton reaction system. These results indicate a possible role for the use of 5ß-scymnol, either alone or concomitant with NAC, in the prevention of hepatic necrosis following toxic doses of APAP.