HEPATOPROTECTIVE EFFECTS OF THE SHARK BILE-SALT 5-BETA-SCYMNOL ON ACETAMINOPHEN-INDUCED LIVER-DAMAGE IN MICE

The hepatoprotective effect of the shark bile salt 5 beta-scymnol has been studied in the model of acute hepatotoxicity induced by administr ation of acetaminophen (APAP, paracetamol). 5 beta-Scymnol at doses of 20, 35, and 70 mg/kg intraperitoneally tip) decreased significantly t he 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 5 beta-scymnol remained hepatoprote ctive when administered 4 hr after the APAP overdose. N-Acetylcysteine (NAG) is protective against APAP-induced hepatotoxicity at 250 and 50 0 mg/kg tip) when administered up to 3 hr after APAP overdose, as show n by a significant reduction in serum enzyme activity. Coadministratio n of 5 beta-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 5 beta-scymnol treatment alone. I n addition, 5 beta-scymnol has potent hydroxyl radical quenching activ ity as it markedly inhibited deoxyribose degradation in a ferrous/asco rbate Fenton reaction system. These results indicate a possible role f or the use of 5 beta-scymnol, either alone or concomitant with NAG, in the prevention of hepatic necrosis following toxic doses of APAP. (C) 1996 Society of Toxicology