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

Fed Proc. 1980 Nov;39(13):3118-23.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acidosis / complications*
  • Alanine Transaminase / metabolism
  • Animals
  • Butylene Glycols
  • Carbon Tetrachloride Poisoning / chemically induced*
  • Chemical and Drug Induced Liver Injury*
  • Chloroform*
  • Diabetes Complications
  • Drug Synergism
  • Ketones*
  • Ketosis / complications*
  • Liver Diseases / complications
  • Rats

Substances

  • Butylene Glycols
  • Ketones
  • Chloroform
  • Alanine Transaminase