Site-specific therapeutic effects of protease inhibitors: effect of route of administration in experimental pancreatitis.
Inappropriate local and systemic activation of trypsin arising from trypsinogen mediates key steps in the pathogenesis of acute pancreatitis. Trypsin presumably causes direct injury to cells, but also activates other proteases and causes secondary effects such as inducing the expression of adhesion molecules on endothelium and leukocytes, and stimulating leukocytes to secrete cytokines, tissue-damaging enzymes, oxygen radicals and matrix metalloproteinases. Protease inhibition interferes with this cascade of events. Here we review experimental studies on protease inhibition and their potential application and report our findings of site-specific therapeutic effects of the novel protease inhibitor nafamostat (FUT-175) in experimental acute pancreatitis.
Department of Surgery, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, WHT 506, Boston, MA 02114, USA. TKeck@partners.org
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D000818:Animals; D001550:Benzamidines; D004195:Disease Models, Animal; D006146:Guanidines / Q000494:pharmacology*; D007262:Infusions, Intravenous; D019283:Pancreatitis, Acute Necrotizing / Q000188:drug therapy*; D011480:Protease Inhibitors / Q000494:pharmacology*
D001550:Benzamidines; D006146:Guanidines; D011480:Protease Inhibitors; C032855:nafamostat