Modification of haloalkane-induced hepatotoxicity by exogenous ketones and metabolic ketosis.

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.