Effect of ethanol on carbon tetrachloride levels and hepatotoxicity after acute carbon tetrachloride poisoning.
To study the effect of an acute dose of ethanol on carbon tetrachloride (CCl4) concentration and hepatotoxicity, female rats received ethanol (2.5 ml/kg body wt.) either intragastrically or intraperitoneally following intragastric administration of CCl4 (1.5 ml/kg body wt.). Three hours after acute CCl4 intoxication there was a striking increase in CCl4 concentration in animals treated simultaneously with ethanol intragastrically compared to those receiving ethanol intraperitoneally. This increase was significant (P less than 0.05) and amounted to 211% for blood, 236% for liver and 405% for fat tissue, whereas animals treated with CCl4 alone showed CCl4 concentrations in the range between the two other experimental groups. Serum activities of glutamate oxalacetate transaminase, glutamate pyruvate transaminase and glutamate dehydrogenase were found to be considerably higher in animals treated with the combination of CCl4 and ethanol when compared to those receiving CCl4 alone, showing that ethanol given intraperitoneally or intragastrically enhances CCl4 hepatotoxicity. Since the intraperitoneal administration of ethanol led to a reduction rather than an increase in CCl4 concentration in the early phase of intoxication, additional mechanisms independent of actual levels of CCl4, such as direct effects of ethanol on the CCl4 metabolizing enzyme of the membrane of the endoplasmic reticulum, have to be implicated in the pathogenesis of the potentiation of CCl4 hepatotoxicity by ethanol.
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002251:Carbon Tetrachloride / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D002252:Carbon Tetrachloride Poisoning / Q000097:blood / Q000201:enzymology / Q000378:metabolism*; D004357:Drug Synergism; D000431:Ethanol / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D005969:Glutamate Dehydrogenase / Q000097:blood; D007274:Injections, Intraperitoneal; D007441:Intubation, Gastrointestinal; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D000431:Ethanol; D002251:Carbon Tetrachloride; D005969:Glutamate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase