Studies on carbon tetrachloride-ethanol interactions in mice

Abstract

Male C57BL/6J (C57) and DBA/2J (DBA) inbred mice were dosed with either corn oil or carbon tetrachloride (CCLQ in corn oil 24 h before a 3.25 g kg i.p. dose of ethanol. The CCL 4 doses were increased in approximate half-log intervals ( 5, 15, 50, 150 or 500 μl kg , intragastrically (i.g.)). Blood acetaldehyde concentrations were significantly increased l, 2, 3 and 4 h after ethanol administration at Ccl 4 doses of 15 μl kg and higher, with DBA and C57 mice exhibiting similar dose-response effects up to the 150 μl kg dose. A CCl 4 dose of 500 μl kg produced differences in blood acetaldehyde elevation between the two inbred strains (DBA—5-fold, C57—3-fold). Associated with the elevation of blood acetaldehyde content was a decrease in the rate of elimination of ethanol from blood. Using male genetically heterogeneous stock (HS) mice it was shown that phenobarbital pretreatment potentiated the CCl 4-induced decrease in in vivo acetaldehyde oxidation. An equimolar dose of CHCl 3 ( 0.5 mmol kg ) was without effect in either control or phenobarbital-pretreated mice. Mice pretreated with 0.5 mmol kg , i.g., 1,2-dichloroethane, 1,1,2-trichloroethylene or bromobenzene did not exhibit significant interaction with ethanol. These data show that in vivo acetaldehyde oxidation is inhibited by very low doses of CCl 4 ( 15 μl kg , i.g.) and that this inhibition is enhanced by the cytochrome P-450-inducing agent phenobarbital.