Inhibition of ethanol-induced liver disease in the intragastric feeding rat model by chlormethiazole

The purpose of this investigation was to assess the effect of chlormethiazo le treatment on liver damage in the experimental rat intragastric ethanol-f eeding model of alcoholic liver disease. Chlormethiazole has been used in t he treatment of alcoholic withdrawal and has been shown to inhibit cytochro me P4502E1, Since treatment of experimental alcoholic liver disease with CY P2E1 inhibitors had an ameliorating effect on liver injury in the rat, chlo rmethiazole was used to see if it had a similar effect. Rats fed ethanol fo r 2 months had significantly less liver injury when chlormethiazole was add ed to the diet, fed intragastrically. The CYP2E1 apoprotein levels, which w ere increased by ethanol feeding, were also increased when chlormethiazole was fed with ethanol. Chlormethiazole inhibited the Increase in the ethanol -induced CYP2E1 activity in vivo, as measured by chlorzoxazone B-hydroxylat ion, but did not effect the level of CYP2E1 apoprotein, Likewise, the reduc tion in proteasome proteolytic enzyme activity produced by ethanol feeding was blunted in chlormethiazole-fed rats. These results support the conclusi on that chlormethiazole treatment partially protects the liver from injury by inhibiting CYP2E1 activity in vivo.