Assessment of the minimal effective dose of acetone for potentiation of the hepatotoxicity induced by trichloroethylene-carbon tetrachloride mixtures.
Administration of acetone to rats in amounts larger than or equal to a minimal effective dosage (MED) is known to potentiate the severity of the liver damage produced by CCl4 alone. It has been reported that CCl4-induced hepatotoxicity is also enhanced by the previous administration of trichloroethylene (TCE). In addition, TCE-CCl4 mixture-induced liver injury is potentiated by acetone. The present study was undertaken to determine if the acetone MED is decreased when the haloalkane challenge is a mixture of TCE-CCl4 instead of CCl4 alone. The effect of varying mixture compositions was also evaluated. In a first series of experiments, male Sprague-Dawley rats received corn oil or acetone (0.05-0.25 ml/kg, po); 18 hr later, they received an ip injection of either CCl4 (0.1 ml/kg) or [TCE (0.25 ml/kg)-CCl4 (0.1 ml/kg)]. In a second series, rats received corn oil or acetone (0.75 ml/kg), and were challenged with TCE (1.5 ml/kg), CCl4 (0.25 ml/kg), or a mixture of TCE-CCl4, where TCE and CCl4 dosages were equal to 25-75%, 50-50%, and 75-25%, respectively, of those used for the administration of the solvents alone. In both series, rats were killed 24 hr after the haloalkane challenge. Liver injury was assessed biochemically (plasma ALT activities and bilirubin concentrations) and morphologically. When TCE was added to a solution of CCl4, smaller doses of CCl4 were required to produce equally severe liver injury.(ABSTRACT TRUNCATED AT 250 WORDS)
Charbonneau
M
M
Département de Pharmacologie, Faculté de Médecine, Université de Montréal, Québec, Canada.
Perreault
F
F
Greselin
E
E
Brodeur
J
J
Plaa
G L
GL
D000096:Acetone / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D002251:Carbon Tetrachloride / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury / Q000503:physiopathology*; D004357:Drug Synergism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014241:Trichloroethylene / Q000633:toxicity*
D000096:Acetone; D014241:Trichloroethylene; D002251:Carbon Tetrachloride; D001219:Aspartate Aminotransferases; D001663:Bilirubin