Alcoholic pancreatitis in rats fed ethanol in a nutritionally adequate liquid diet.
In an effort to develop a model of chronic alcoholic pancreatitis in Sprague-Dawley rats fed a nutritionally adequate diet, 3 groups of 15 animals each were fed Wayne Rodent-Blox ad libitum, Lieber-DeCarli diet with 40% of carbohydrate calories replaced by ethanol ad libitum and isocaloric amounts of Lieber-DeCarli diet respectively for a period of 18 months. Rats were anesthetized and basal and secretin-stimulated pancreatic juice was obtained. Pancreatic glands were isolated and divided into portions for histology, biochemical analyses, and cell fractionation. The homogenate, zymogen granule fraction, mitochondrial-lysosomal fraction, microsomal fraction and postmicrosomal supernatant as well as aliquots of pancreatic juice were analyzed for cathepsin B, acid phosphatase, beta-D-glucoronidase, arylsulphatase and leucine naphthylamidase. All of the ethanol-fed animals developed morphological changes akin to human chronic pancreatitis. There were focal areas of parenchymal degeneration with fibrosis, protein plug formation and tubular complexes. In the pancreatic tissue of animals fed ethanol, total protein, trypsinogen (and free trypsin) were increased and amylase was decreased. While acid phosphatase was increased in all of the particulate fractions, cathepsin B was increased in the zymogen granule and mitochondrial-lysosomal fractions. Basal and post-secretin pancreatic juice did not show a significant increase in digestive or lysosomal enzymes. It is suggested that focal degenerative changes may be due to trypsin generated by intracellular activation of digestive enzymes by lysosomal enzyme cathepsin B.
D000135:Acid Phosphatase / Q000378:metabolism; D000681:Amylases / Q000378:metabolism; D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D002401:Cathepsin B / Q000378:metabolism; D002908:Chronic Disease; D004195:Disease Models, Animal; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity*; D005526:Food, Formulated; D010179:Pancreas / Q000201:enzymology / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D014357:Trypsin / Q000378:metabolism; D014362:Trypsinogen / Q000378:metabolism
D000431:Ethanol; D014362:Trypsinogen; D000135:Acid Phosphatase; D000681:Amylases; D014357:Trypsin; D002401:Cathepsin B