Hepatoprotective effects of the shark bile salt 5beta-scymnol on acetaminophen-induced liver damage in mice.
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.
Macrides
T A
TA
Biochemistry Unit, RMIT-University, Melbourne, Victoria, 3001, Australia.
Naylor
L M
LM
Kalafatis
N
N
Shihata
A
A
Wright
P F
PF
D000082:Acetaminophen; D000111:Acetylcysteine / Q000627:therapeutic use; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001647:Bile Acids and Salts / Q000737:chemistry / Q000627:therapeutic use*; D056486:Chemical and Drug Induced Liver Injury; D002777:Cholestanols / Q000737:chemistry / Q000627:therapeutic use*; D007274:Injections, Intraperitoneal; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000473:pathology; D008107:Liver Diseases / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D009336:Necrosis
D001647:Bile Acids and Salts; D002777:Cholestanols; D000082:Acetaminophen; C074469:scymnol; D007770:L-Lactate Dehydrogenase; D000410:Alanine Transaminase; D000111:Acetylcysteine