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  • Title: Effect of the oral administration of sepimostat mesilate on cerulein induced acute pancreatitis in rats.
    Author: Wang ZH, Manabe T, Ohshio G, Hirano T, Okada N, Imamura T, Kawaguchi Y, Yotsumoto F, Yamaki K, Imamura M.
    Journal: Arzneimittelforschung; 1995 Oct; 45(10):1082-6. PubMed ID: 8595064.
    Abstract:
    The effect of a potent protease inhibitor, sepimostat mesilate (CAS 103926-82-5, FUT-187), on acute interstitial edematous pancreatitis induced by a supramaximal dose of cerulein, a cholecystokinin (CCK) analogue, was evaluated. The serum amylase activity increased 18-fold over normal control after the infusion of cerulein at 5 micrograms/kg/h for 6 h. The serum lipase activity showed a 235-fold increase. An elevated pancreatic water content, pancreatic interstitial edema, inflammatory infiltration and vacuolization of the acinar cells were found. Redistribution of cathepsin B shifted from the lysosomal pellet fraction to the zymogen granule pellet fraction was noted in the early stages. All these parameters of pancreatitis mentioned above were inhibited by FUT-187 pretreatment at doses of 30 to 300 mg/kg. These observations suggest that FUT-187 inhibits the redistribution of cathepsin B shift from the lysosomal fraction to the zymogen fraction in cerulein-induced acute pancreatitis and improves the parameters of acute pancreatitis.
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