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Acute hemorrhagic pancreatic necrosis in mice. Effects of proteinase inhibitors on its induction.

An acute hemorrhagic pancreatitis with fat necrosis (AHPN) was induced in female mice fed a choline-deficient diet containing 0.5% DL-ethionine. The effect of various proteinase inhibitors on the induction of the pancreatitis was evaluated using three parameters, the mortality of the animals, the appearance before death of a shock-like state, and the severity of the pancreatic pathology. Treatment of the animals with leupeptin, pepstatin, chymostatin and/or antipain, proteinase inhibitors of microbial origin, resulted in a distinct attenuation of the severity of the induced process, whereas aprotinin and chloroquine had no effect. The results indicate that use of the microbial proteinase inhibitors should be considered as potential therapeutic agents in cases of pancreatitis.