Amelioration of rat cerulein pancreatitis by guamerin-derived peptide, a novel elastase inhibitor

Increased activity of various proteases is observed in both human and exper imental pancreatitis; however, the information on the effects of specific p rotease inhibitors on the disease is limited. In this study we show that a novel elastase inhibitor, guamerin-derived synthetic peptide (GDSP), improv es the parameters of cerulein-induced acute pancreatitis in the rat. The ef fects of GDSP on pancreatic weight, serum amylase and lipase, morphologic c hanges in the pancreas, neutrophil infiltration, and nuclear factor kappa B (NF-kappa B) activation were measured in rats infused with supramaximal do se of cerulein (5 (g/kg/h) for 6 h. The effects of GDSP were also measured on superoxide formation by activated human neutrophils. The effects of GDSP were compared with those of another elastase inhibitor, elastatinal. GDSP significantly inhibited edema formation, neutrophil infiltration, acinar ce ll damage, and plasma lipase and amylase increases caused by cerulein. GDSP also completely inhibited superoxide formation in the human neutrophils st imulated by N-formyl-methionine-leucine-phenylalanine (fMLP) or 12-O-tetrad ecanoylphorbol-13-acetate (TPA). Elastatinal had some of the same effects a s GDSP but was less potent and effective. These results demonstrate a benef icial effect of GDSP, a novel specific elastase inhibitor, on the developme nt of rat cerulein pancreatitis.