The influence of ethanol pretreatment on the effects of nine hepatotoxic agents.
The hepatotoxic effects of carbon tetrachloride (0.01 ml/kg i.p.), thioacetamide (50 mg/kg intraperitoneally), paracetamol (0.5 g/kg intraperitoneally), and allyl alcohol (0.05 ml/kg intraperitoneally) as estimated by determination of serum enzyme activities (GOT, GPT, SDH) were enhanced in mice treated with one oral dose of 4.8 g/kg ethanol 16 hrs. previously. Pretreatment of mice with ethanol did not increase the hepatotoxic actions of bromobenzene (0.25 ml/kg intraperitoneally), phalloidin (1.5 mg/kg intraperitoneally), alpha-amanitin (0.75 mg/kg intraperitoneally), and praseodymium (12 mg/kg intravenously) though there was a trend to higher enzyme activities in the case of bromobenzene. In guinea-pigs ethanol also aggravated CCl4-induced liver damage, but only strengthened the hepatotoxic activity of D-galactosamine (150 mg/kg intraperitoneally). Treatment with 4.8 g/kg ethanol did not influence liver glutathione levels in mice but increased aniline hydroxylation in the 9000 x g liver homogenate supernatant of mice and guinea-pigs. A dose of 2.4 g/kg ethanol, on the other hand, neither increased aniline hydroxylase activity nor enhanced carbon tetrachloride-induced hepatotoxicity in mice. It is assumed that the enhanced sensitivity to hepatotoxic agents after treatment with ethanol may be due to an enhanced microsomal activation of these substances.
D000082:Acetaminophen / Q000506:poisoning; D000284:Administration, Oral; D000410:Alanine Transaminase / Q000097:blood; D000435:Alcoholic Intoxication; D000546:Amanitins / Q000506:poisoning; D000815:Aniline Hydroxylase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001969:Bromobenzenes / Q000506:poisoning; D002252:Carbon Tetrachloride Poisoning; D056486:Chemical and Drug Induced Liver Injury; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D005688:Galactosamine / Q000506:poisoning; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007064:L-Iditol 2-Dehydrogenase / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000201:enzymology; D009929:Organ Size / Q000187:drug effects; D010590:Phalloidine / Q000506:poisoning; D011221:Praseodymium / Q000506:poisoning; D013853:Thioacetamide / Q000506:poisoning
D000546:Amanitins; D001969:Bromobenzenes; D013853:Thioacetamide; D010590:Phalloidine; D000082:Acetaminophen; D000431:Ethanol; D005688:Galactosamine; D007064:L-Iditol 2-Dehydrogenase; D000815:Aniline Hydroxylase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione; D011221:Praseodymium