Acetone potentiation of 1,1,2-trichloroethane hepatotoxicity.
Acetone potentiation of 1,1,2-trichloroethane (TCEA) hepatotoxicity was found to be strongly dose-dependent for both acetone and TCEA. An oral dose of 0.5 ml of acetone/kg was the most effective potentiating pretreatment when administered 16 h prior to TCEA. Surprisingly, higher doses of acetone did not potentiate the hepatotoxicity of TCEA, but may have decreased the severity of this toxicity. Acetone potentiation of hepatotoxicity was most pronounced at or near the hepatotoxic threshold for TCEA. While acetone treatment alone did not affect hepatic glutathione (GSH) stores the most consistent effect produced by acetone pretreatment was a significant potentiation of TCEA-induced depletion of hepatic GSH. These findings suggest that critical doses of acetone may enhance the subsequent hepatotoxicity of TCEA via mechanisms that affect the interaction of TCEA and hepatic GSH stores.
D000096:Acetone / Q000633:toxicity*; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000473:pathology; D004357:Drug Synergism; D005978:Glutathione / Q000378:metabolism; D006843:Hydrocarbons, Chlorinated / Q000633:toxicity*; D008099:Liver / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014240:Trichloroethanes / Q000633:toxicity*
D006843:Hydrocarbons, Chlorinated; D014240:Trichloroethanes; D000096:Acetone; C024567:1,1,2-trichloroethane; D000410:Alanine Transaminase; D005978:Glutathione