Gastroprotection by 4-methylpyrazole against ethanol in humans

Digestive Diseases and Sciences
G IaquintoS Szabo

Abstract

4-Methylpyrazole (4-MP), a specific inhibitor of alcohol dehydrogenase, exerts gastroprotection of unusually long duration in rats. We tested the hypothesis that pretreatment with 4-MP might protect the human gastric mucosa against alcohol-induced acute injury. Fourteen healthy volunteers received pretreatment with either 4-MP, 15 mg/kg body weight dissolved in 50 ml of orange juice, or placebo and 2 hr later 100 ml of 40% ethanol. The endoscopic appearance of the gastric mucosa was evaluated and scored (scale 0-5) and mucosal biopsies were obtained just before pretreatment and 30 min after ethanol for histologic examination and prostaglandin E2 measurement. In the 4-MP group the mean endoscopic injury score was significantly lower than that in placebo group, in both the body and the antrum. Histologically, 4-MP significantly reduced disruption of surface epithelium and completely prevented the deep hemorrhagic mucosal lesions. In the 4-MP group no changes in gastric mucosal PGE2 levels were detected. In rats, 4-MP did not inhibit gastric acid output, whereas it markedly increased the adherent gastric mucus evaluated by the alcian blue recovery method. When lipid peroxidation was induced by carbon tetrachloride in hepatic micro...Continue Reading

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