Hepatoprotective effects of the shark bile salt 5beta-scymnol on acetaminophen-induced liver damage in mice.

Abstract

The hepatoprotective effect of the shark bile salt 5beta-scymnol has been studied in the model of acute hepatotoxicity induced by administration of acetaminophen (APAP, paracetamol). 5beta-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 5beta-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 5beta-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 5beta-scymnol treatment alone. In addition, 5beta-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 5beta-scymnol, either alone or concomitant with NAC, in the prevention of hepatic necrosis following toxic doses of APAP.