Ethanol potentiation of carbon tetrachloride hepatotoxicity: Possible role for the in vivo inhibition of aldehyde dehydrogenase

Abstract

1. 1. A potentiation of CCl4-induced hepatotoxicity was observed in rats pretreated with ethanol 18 hr prior to CCl4 exposure.2. 2. Hepatic microsomal aldehyde dehydrogenase (pLDH) was significantly inhibited in animals sacrificed 1 hr following the sequential exposure, however, no more so than in those animals receiving CCl4 alone.3. 3. The animals receiving ethanol alone had ALDH activity similar to vehicle treated controls.4. 4. Twenty-four hours following a potentiating dose of ethanol and CCl4 an 81 and 57% decline in NAD+-dependent microsomal and mitochondrial ALDH activity was observed, respectively.5. 5. Similar results were observed for microsomal and mitochondrial NADP+-dependent ALDH activity.6. 6. The decline in membrane-bound ALDH was greater in potentiated animals than in those receiving CCl4 alone.7. 7. A relatively smaller decline in cytosolic ALDH activity was observed in CCl4 treated rats with or without ethanol pre-exposure.8. 8. The data suggest that inhibition of membrane bound ALDH may be one of the major mechanisms of in vivo potentiation of CCl4-induced hepatotoxicity by ethanol.