Increased activity of various
proteases is observed in both human and experimental
pancreatitis; however, the information on the effects of specific
protease inhibitors on the disease is limited. In this study we show that a novel
elastase inhibitor,
guamerin-derived synthetic
peptide (GDSP), improves the parameters of
cerulein-induced
acute pancreatitis in the rat. The effects of GDSP on pancreatic weight, serum
amylase and
lipase, morphologic changes in the pancreas, neutrophil infiltration, and nuclear factor KB (
NF-KB) activation were measured in rats infused with supramaximal dose 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 cell damage, and plasma
lipase and
amylase increases caused by
cerulein. GDSP also completely inhibited
superoxide formation in the human neutrophils stimulated by N-formyl-
methionine-
leucine-phenyl-
alanine (fMLP) or 12-O-tetradecanoylphorbol-13-
acetate (TPA).
Elastatinal had some of the same effects as GDSP but was less potent and effective. These results demonstrate a beneficial effect of GDSP, a novel specific
elastase inhibitor, on the development of rat
cerulein pancreatitis.