Studies on carbon tetrachloride-ethanol interactions in mice.
Male C57BL/6J (C57) and DBA/2J (DBA) inbred mice were dosed with either corn oil or carbon tetrachloride (CCl4) in corn oil 24 h before a 3.25 g/kg i.p. dose of ethanol. The CCl4 doses were increased in approximate half-log intervals (5, 15, 50, 150 or 500 microliter/kg, intragastrically (i.g.)). Blood acetaldehyde concentrations were significantly increased 1, 2, 3 and 4 h after ethanol administration at CCl4 doses of 15 microliter/kg and higher, with DBA and C57 mice exhibiting similar dose-response effects up to the 150 microliter/kg dose. A CCL4 dose of 500 microliter/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 rat of elimination of ethanol from blood. Using male genetically heterogeneous stock (HS) mice it was shown that phenobarbital pretreatment potentiated the CCl4-induced decrease in in vivo acetaldehyde oxidation. An equimolar dose of CHCl3 (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 CCl4 (15 microliter/kg, i.g.) and that this inhibition is enhanced by the cytochrome P-450-inducing agent phenobarbital.
D000079:Acetaldehyde / Q000097:blood; D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity*; D004347:Drug Interactions; D000431:Ethanol / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010634:Phenobarbital / Q000494:pharmacology
D000431:Ethanol; D002251:Carbon Tetrachloride; D000079:Acetaldehyde; D010634:Phenobarbital