Development of an animal model of chronic alcohol-induced pancreatitis in the rat.
This study was designed to develop an animal model of alcoholic pancreatitis and to test the hypothesis that the dose of ethanol and the type of dietary fat affect free radical formation and pancreatic pathology. Female Wistar rats were fed liquid diets rich in corn oil (unsaturated fat), with or without a standard or high dose of ethanol, and medium-chain triglycerides (saturated fat) with a high dose of ethanol for 8 wk enterally. The dose of ethanol was increased as tolerance developed, which allowed approximately twice as much alcohol to be delivered in the high-dose group. Serum pancreatic 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 levels were elevated significantly by the high ethanol dose. Increases were blunted significantly by dietary saturated fat. Fibrosis and collagen alpha1(I) expression in the pancreas were not detectable after 4 wk of enteral ethanol feeding; however, they were enhanced significantly by the high dose after 8 wk. Furthermore, radical adducts detected by electron spin resonance were minimal with the standard dose; however, the high dose increased carbon-centered radical adducts as well as 4-hydroxynonenal, an index of lipid peroxidation, significantly. Radical adducts were also blunted by approximately 70% by dietary saturated fat. The animal model presented here is the first to demonstrate chronic alcohol-induced pancreatitis in a reproducible manner. The key factors responsible for pathology are the amount of ethanol administered and the type of dietary fat.
Kono
H
H
Laboratory of Hepatobiology and Toxicology, Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7365, USA.
Nakagami
M
M
Rusyn
I
I
Connor
H D
HD
Stefanovic
B
B
Brenner
D A
DA
Mason
R P
RP
Arteel
G E
GE
Thurman
R G
RG
D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D002908:Chronic Disease; D004041:Dietary Fats / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology; D005227:Fatty Acids / Q000494:pharmacology; D005260:Female; D005355:Fibrosis; D005609:Free Radicals / Q000037:antagonists & inhibitors / Q000378:metabolism; D007150:Immunohistochemistry; D008099:Liver / Q000187:drug effects / Q000473:pathology; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019512:Pancreatitis, Alcoholic / Q000378:metabolism* / Q000473:pathology*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000447:Aldehydes; D004041:Dietary Fats; D005227:Fatty Acids; D005609:Free Radicals; D011506:Proteins; D000431:Ethanol; C027576:4-hydroxy-2-nonenal