title: Modification of haloalkane-induced hepatotoxicity by exogenous ketones and metabolic ketosis.
abstract: A variety of chemicals potentiate haloalkane-induced liver injury, but structure-activity relationships are not apparent. Recent studies have shown that one structural determinant, a carbonyl moiety, is common to several potentiating agents. Thus five ketonic chemicals (acetone, 2-butanone, methyl n-butylketone, 2,5-hexanedione, Kepone) and three chemicals that are metabolized to ketones (isopropranol, 2-butanol, n-hexane) potentiate the liver injury produced by one or more haloalkanes. Potentiation also has been observed when haloalkanes are administered to animals in a state of metabolic ketosis produced by alloxan-induced diabetes or by 1,3-butanediol administration. These observations are consistent with the hypothesis that administration or generation of ketonic substances increases the susceptibility of the liver to the toxic actions of haloalkanes.
mesh_terms: D000138:Acidosis / Q000150:complications*; D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D002072:Butylene Glycols; D002252:Carbon Tetrachloride Poisoning / Q000139:chemically induced*; D056486:Chemical and Drug Induced Liver Injury; D002725:Chloroform; D048909:Diabetes Complications; D004357:Drug Synergism; D007659:Ketones; D007662:Ketosis / Q000150:complications*; D008107:Liver Diseases / Q000150:complications; D051381:Rats
chemical_list: D002072:Butylene Glycols; D007659:Ketones; D002725:Chloroform; D000410:Alanine Transaminase