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 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.