Decreased in vivo acetaldehyde oxidation and hepatic aldehyde dehydrogenase inhibition in C57BL and DBA mice treated with carbon tetrachloride

Abstract

Male C57BL 6J (C57) and DBA 2J (DBA) mice were dosed with 500 μl/kg ig CCl 4, 24 hr before a 3.25 g/kg ip dose of ethanol. The relative bioavailability of CCl 4 was similar in both mouse strains. CCl 4 pretreatment produced genotypically related decreases in blood ethanol elimination rates with DBA mice showing the greater decrease. Blood acetaldehyde concentrations were significantly elevated in the CCl 4-pretreated animals of both strains. DBA CCl 4-pretreated mice exhibited significantly higher blood acetaldehyde concentrations than C57 mice 1, 2, 3, and 4 hr after ethanol administration. CCl 4 pretreatment resulted in acetaldehyde elevations of approximately threefold in C57 mice four- to fivefold in DBA mice. Four hours after the ethanol dose, animals were sacrificed for enzymatic analyses of hepatic aldehyde dehydrogenase (ALDH) and alcohol dehydrogenase (ADH) activity. The specific activities and activity per gram of cytosolic and mitochondrial ALDH were decreased in both mouse strains. ADH activity was not significantly altered by CCl 4 pretreatment. Liver necrosis, as measured by serum alanine aminotransferase activity, was similar in both strains (approx fivefold increase). These data indicate that CCl 4 increased blood acetaldehyde concentrations by inhibiting hepatic cytosolic and mitochondrial ALDH and that the degree of blood acetaldehyde elevation is different in the two inbred mouse strains C57 and DBA.