Development of an animal model of chronic alcohol-induced pancreatitis in the rat

This study was designed to develop an animal model of alcoholic pancreatiti s and to test the hypothesis that the dose of ethanol and the type of dieta ry fat affect free radical formation and pancreatic pathology. Female Wista r rats were fed liquid diets rich in corn oil (unsaturated fat), with or wi thout a standard or high dose of ethanol, and medium-chain triglycerides (s aturated fat) with a high dose of ethanol for 8 wk enterally. The dose of e thanol was increased as tolerance developed, which allowed approximately tw ice as much alcohol to be delivered in the high-dose group. Serum pancreati c enzymes and histology were normal after 4 wk of diets rich in unsaturated fat, with or without the standard dose of ethanol. In contrast, enzyme lev els were elevated significantly by the high ethanol dose. Increases were bl unted significantly by dietary saturated fat. Fibrosis and collagen alpha1( I) expression in the pancreas were not detectable after 4 wk of enteral eth anol feeding; however, they were enhanced significantly by the high dose af ter 8 wk. Furthermore, radical adducts detected by electron spin resonance were minimal with the standard dose; however, the high dose increased carbo n-centered radical adducts as well as 4-hydroxynonenal, an index of lipid p eroxidation, significantly. Radical adducts were also blunted by similar to 70% by dietary saturated fat. The animal model presented here is the first to demonstrate chronic alcohol-induced pancreatitis in a reproducible mann er. The key factors responsible for pathology are the amount of ethanol adm inistered and the type of dietary fat.