Alcoholic pancreatitis in rats: Injury from nonoxidative metabolites of ethanol

Jens Werner, Mouris Saghir, Andrew L. Warshaw, Kent B. Lewandrowski, Michael Laposata, Renato V. Iozzo, Edward A. Carter, Richard J. Schatz, Carlos Fernández-del Castillo

Research output: Contribution to journalArticle

89 Scopus citations

Abstract

The mechanism by which alcohol injures the pancreas remains unknown. Recent investigations suggest a role for fatty acid ethyl ester (FAEE), a nonoxidative metabolite of ethanol, in the pathogenesis of alcohol pancreatitis. In this study, we characterized ethanol-induced injury in rats and evaluated the contribution of oxidative and nonoxidative ethanol metabolites in this form of acute pancreatitis. Pancreatic injury in rats was assessed by edema, intrapancreatic trypsinogen activation, and microscopy after infusing ethanol with or without inhibitors of oxidative ethanol metabolism. Plasma and tissue levels of FAEE and ethanol were measured and correlated with pancreatic injury. Ethanol infusion generated plasma and tissue FAEE and, in a dose-dependent fashion, induced a pancreas-specific injury consisting of edema, trypsinogen activation, and formation of vacuoles in the pancreatic acini. Inhibition of the oxidation of ethanol significantly increased both FAEE concentration in plasma and pancreas and worsened the pancreatitis-like injury. This study provides direct evidence that ethanol, through its nonoxidative metabolic pathway, can produce pancreas-specific toxicity in vivo and suggests that FAEE are responsible for the development of early pancreatic cell damage in acute alcohol-induced pancreatitis.

Original languageEnglish (US)
Pages (from-to)G65-G73
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume283
Issue number1 46-1
StatePublished - Jul 2 2002
Externally publishedYes

Keywords

  • Ethanol metabolism
  • Fatty acid ethyl ester
  • Pathophysiology

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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  • Cite this

    Werner, J., Saghir, M., Warshaw, A. L., Lewandrowski, K. B., Laposata, M., Iozzo, R. V., Carter, E. A., Schatz, R. J., & Fernández-del Castillo, C. (2002). Alcoholic pancreatitis in rats: Injury from nonoxidative metabolites of ethanol. American Journal of Physiology - Gastrointestinal and Liver Physiology, 283(1 46-1), G65-G73.