Effect of verapamil on allyl alcohol hepatotoxicity

The effects of verapamil, a calcium channel blocker, on allyl alcohol (AA) hepatotoxicity were studied in vivo. AA administration induced an increase of serum alanine aminotransferase (ALT) concentration and liver necrosis by means of glutathione (GSH) depletion. Pretreatment with verapamil reduced the increase of ALT in plasma and the morphological signs of necrosis induced by AA administration. Verapamil did not affect GSH levels by itself but prevented the decrease of the tripeptide by AA. In vitro, but not in vivo, verapamil inhibited the activity of alcohol dehydrogenase (ADH), the key enzyme in the conversion of AA into the toxic metabolite acrolein. These data indicate that verapamil protects against AA toxicity, probably by preventing the production of acrolein, its reactive metabolite.