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Gastroprotection by 4-Methylpyrazole Against Ethanol in Humans

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Abstract

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.

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Authors
  1. Gaetano Iaquinto
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  2. Mario Del Tacca
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  3. Luigi Cuccurullo
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  4. Maria Caterina Parodi
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  5. Nicola Giardullo
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  6. Vittorio D'Onofrio
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  7. Gianfranco Natale
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  8. Diego Carignani
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  9. Franca Ferraraccio
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  10. Sandor Szabo
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Iaquinto, G., Tacca, M.D., Cuccurullo, L. et al. Gastroprotection by 4-Methylpyrazole Against Ethanol in Humans. Dig Dis Sci 43, 816–825 (1998). https://doi.org/10.1023/A:1018878400935

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