Effect of Disulfiram on Canine Liver Aldehyde Dehydrogenase Activity: In Vivo Inactivation in a Nonrodent Animal Model

Abstract

Dogs were used as nonrodent animal models to study the in vivo effects of disulfiram on hepatic aldehyde dehydrogenase (ALDH) activity. Dogs were treated with disulfiram either intraperitoneally or orally (100 mg/kg/day for 2 days followed by 40 mg/kg/day for 3 days). Liver biopsies from control and treated animals were fractionated by differential centrifugation and the subcellular fractions were analyzed for ALDH activity. Significantly less activity was observed in cell homogenates from treated animals (20-50% of control activity per gram of liver). The majority of loss in activity was accounted for by a decrease in ALDH activity in the soluble fraction of the cell (12-30% of control activity) and in the mitochondrial fraction (23-30% of control activity). Activities at both high (5 mM) and low (50 microM) acetaldehyde concentrations were affected. The subcellular distribution of ALDH activity and in vivo inhibition by disulfiram in dogs is different from that reported for rats.