Gastroprotection by 4-Methylpyrazole Against Ethanol in Humans

4-Methylpyrazole (4-MP), a specific inhibitor ofalcohol dehydrogenase, exerts gastroprotection ofunusually long duration in rats. We tested thehypothesis that pretreatment with 4-MP might protect the human gastric mucosa against alcohol-inducedacute injury. Fourteen healthy volunteers receivedpretreatment with either 4-MP, 15 mg/kg body weightdissolved in 50 ml of orange juice, or placebo and 2 hr later 100 ml of 40% ethanol. The endoscopicappearance of the gastric mucosa was evaluated andscored (scale 0-5) and mucosal biopsies were obtainedjust before pretreatment and 30 min after ethanol for histologic examination and prostaglandinE2 measurement. In the 4-MP group the meanendoscopic injury score was significantly lower thanthat in placebo group, in both the body and the antrum.Histologically, 4-MP significantly reduced disruption ofsurface epithelium and completely prevented the deephemorrhagic mucosal lesions. In the 4-MP group nochanges in gastric mucosal PGE2 levels weredetected. In rats, 4-MP did not inhibit gastric acid output,whereas it markedly increased the adherent gastric mucusevaluated by the alcian blue recovery method. When lipidperoxidation was induced by carbon tetrachloride in hepatic microsomes, 4-MP caused significantinhibition of malondialdehyde generation. We concludethat 4-MP provides significant protection of the humanstomach against alcohol-induced acute mucosal injury. 4-MP, besides inhibiting the conversionof alcohol to acetaldehyde, might protect the gastricmucosa by increasing adherent gastric mucus and byscavenging free radicals.