Peptide leukotriene receptor antagonist diminishes pancreatic edema formation in rats with cerulein-induced acute pancreatitis.
BACKGROUND
This study was designed to evaluate the protective effect of a peptide leukotriene receptor antagonist, pranlukast hydrate, against pancreatic injuries during acute pancreatitis.


METHODS
Acute pancreatitis was induced in rats by intravenous infusion of a supramaximal dose of cerulein (5 micrograms/kg h for 4 h). In this model marked hyperamylasemia, a significant increase in pancreatic water content, and a significant increase in pancreatic microvascular leakage of Evans blue dye were observed. Pancreatic subcellular redistribution of the lysosomal enzyme cathepsin B from the lysosomal fraction to the zymogen fraction was also observed.


RESULTS
Pretreatment with pranlukast hydrate at a dose of 10 micrograms/kg (twice, 8 and 4 h before cerulein infusion) significantly inhibited these pancreatic injuries, including hyperamylasemia, increased pancreatic microvascular permeability, and redistribution of cathepsin B in pancreatic acinar cells.


CONCLUSIONS
These results suggest that peptide leukotrienes may be involved in the pathogenesis of acute pancreatitis in the early stage of the disease and that peptide leukotriene receptor antagonist might be of therapeutic value for treatment of acute pancreatitis.
Hirano
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Dept. of Surgery, Hirano Clinic, Osaka, Japan.
D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000818:Animals; D001834:Body Water; D002401:Cathepsin B / Q000378:metabolism; D002108:Ceruletide; D002867:Chromones / Q000627:therapeutic use*; D004487:Edema / Q000209:etiology / Q000517:prevention & control*; D020024:Leukotriene Antagonists; D008297:Male; D010179:Pancreas / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D010182:Pancreatic Diseases / Q000209:etiology / Q000517:prevention & control*; D010195:Pancreatitis / Q000139:chemically induced / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar
D002867:Chromones; D020024:Leukotriene Antagonists; D002108:Ceruletide; D000681:Amylases; D002401:Cathepsin B; C047681:pranlukast