Influence of dietary factors on the pancreatotoxicity of ethionine.

Choline deficiency enhances greatly the pancreatotoxicity of DL-ethionine. Mice fed DL-ethionine with a choline-deficient diet develop a fatal acute hemorrhagic pancreatic necrosis with fat necrosis (AHPN) in 5 days. Induction of the AHPN is completely prevented by dietary methionine and drastically reduced by dietary methionine and drastically reduced by dietary choline. The amount of proteins, carbohydrates, and fat in the diet influences its consumption by the animals and thus the severity of the pancreatic pathology. The histogenesis of the process is characterized by widespread alterations of the membranous organelles of the acinar cells, especially the endoplasmic reticulum and the zymogen granules. The onset of the hemorrhagic necrosis of the pancreas is due to an endogenous intraparenchymal activation of the zymogenic proteases, including proelastase. The new experimental model of AHPN appears to mimic very closely the clinical course, the anatomic pathologic lesions, and the postulated pathogenesis of the corresponding human disease.