Modification of the hepatotoxicity of D-galactosamine in the rat by cycloheximide.
The effect of cycloheximide (1.5 mg/kg), a potent inhibitor of protein biosynthesis, on D-galastosamine (375 mg/kg)-induced hepatic necrosis and hepatic triglyceride accumulation was studied in rats. Serum transaminase levels, 24 hr after D-galactosamine administration, were significantly reduced in animals treated simultaneously or 4 hr before D-galactosamine with cycloheximide, when compared to animals given D-galactosamine alone. Transaminase levels in rats given cycloheximide 4 hr after D-galactosamine were not reduced. Histological grading of hepatocyte necrosis showed a similar pattern of protection in the pretreated and simultaneously treated groups. Hepatic triglycerides were significantly reduced only in the latter group. Fatality 48 hr after D-galactosamine administration was significantly less common in rats pretreated with cycloheximide when compared to rats given D-galactosamine without cycloheximide, and surviving animals in the cycloheximide pretreated group had a lower serum transaminase level, a lower necrosis score, and a reduced hepatic triglyceride level. These data are consistent with the concept that protein synthesis is important in the pathogenesis of D-galactosamine-induced hepatotoxicity.
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury; D003513:Cycloheximide / Q000494:pharmacology*; D005688:Galactosamine / Q000037:antagonists & inhibitors / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008107:Liver Diseases / Q000097:blood / Q000473:pathology; D009336:Necrosis; D014176:Protein Biosynthesis; D051381:Rats; D014280:Triglycerides / Q000378:metabolism
D014280:Triglycerides; D005688:Galactosamine; D003513:Cycloheximide; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase