Studies on carbon tetrachloride-ethanol interactions in mice

• Published in: Toxicology letters Vol. 10; no. 1; p. 17
• Main Authors: Hjelle, J J, Gordon, A S, Petersen, D R
• Format: Journal Article
• Language: English
• Published: Netherlands 01.01.1982
• Subjects: Acetaldehyde - blood; Animals; Carbon Tetrachloride - toxicity; Drug Interactions; Ethanol - metabolism; Liver - drug effects; Liver - metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Phenobarbital - pharmacology
• ISSN: 0378-4274
• DOI: 10.1016/0378-4274(82)90261-2

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.