title: Protective effect of nafamostat mesilate on cellular and lysosomal fragility of acinar cells in rat cerulein pancreatitis.
abstract: This in vivo and in vitro study demonstrates the protective effects of a new synthetic protease inhibitor--nafamostat mesilate, FUT-175--on increased cellular and lysosomal fragility within acinar cells during the early stage of cerulein-induced acute pancreatitis in rats. FUT-175 prevented hyperamylasemia, pancreatic edema, congestion owing to amylase, and lactic dehydrogenase (LDH) discharge from acini as well as cathepsin-B leakage from lysosomes dose-dependently in doses of 1-10 mg/kg.h. These results suggest that FUT-175 can protect against pancreatitis at subcellular levels in lysosomes and cellular or organelle membranes. Proteases may well play the important role in the pathogenesis of acute pancreatitis, and such a low molecular protease inhibitor may be useful clinically in the treatment of acute pancreatitis.
mesh_terms: D000681:Amylases / Q000097:blood; D000818:Animals; D001550:Benzamidines; D002401:Cathepsin B / Q000378:metabolism; D002108:Ceruletide; D006146:Guanidines / Q000494:pharmacology* / Q000627:therapeutic use; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008247:Lysosomes / Q000187:drug effects*; D008297:Male; D010179:Pancreas / Q000187:drug effects*; D010195:Pancreatitis / Q000139:chemically induced / Q000188:drug therapy*; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001550:Benzamidines; D006146:Guanidines; D011480:Protease Inhibitors; D002108:Ceruletide; D007770:L-Lactate Dehydrogenase; D000681:Amylases; D002401:Cathepsin B; C032855:nafamostat