Leukotriene receptor antagonism in experimental acute pancreatitis in rats.
OBJECTIVE
Acute pancreatitis is a multifactorial disease caused by activation of several inflammatory mediators. Leukotrienes, beside other mediators, may be involved in acute pancreatitis. The aim of this study was to investigate the effects of 'zafirlukast', a leukotriene receptor antagonist, in acute pancreatitis and its relation with prostaglandin synthesis.


METHODS
Eighty rats were randomly divided into eight groups. Acute pancreatitis was induced by subcutaneous injection of cerulein (20 microg/kg), four times at 1-h intervals. Zafirlukast (20 mg/kg) was applied intraperitoneally as a pretreatment. Prostaglandin synthesis was inhibited by low-dose indomethacin (5 mg/kg subcutaneously). Pancreatic histopathology, serum amylase activity and pancreatic myeloperoxidase activity were determined to assess the severity of pancreatitis.


RESULTS
Zafirlukast pretreatment alone did not induce any inflammation and fatty necrosis in pancreatic tissue. However, it increased the histopathological score from 3.70 +/- 0.57 to 6.62 +/- 0.53 in rats with acute pancreatitis (P < 0.001). Fatty necrosis was especially prominent in the zafirlukast-treated acute pancreatitis group compared with the untreated group (2.62 +/- 0.26 versus 0.40 +/- 0.22, respectively; P < 0.001). Inhibition of prostaglandin synthesis by indomethacin partially suppressed the harmful effects of zafirlukast in acute pancreatitis. It decreased the pathological score (4.62 +/- 0.73) and fatty necrosis (1.50 +/- 0.32) in that group.


CONCLUSIONS
Interestingly, leukotriene receptor antagonism by zafirlukast increased the pancreatic histopathological score and fatty necrosis in rats with acute pancreatitis. Blocking of cysteinyl leukotriene receptors might cause an induction of mediator synthesis via other pathways. Effects of leukotriene receptor antagonism on the pancreas must be evaluated extensively in further studies.
Oruc
Nevin
N
Department of Gastroenterology, Ege University Faculty of Medicine, Bornova, Izmir, Turkey.
Yukselen
Vahit
V
Ozutemiz
A Omer
AO
Yuce
Gul
G
Celik
Handan Ak
HA
Musoglu
Ahmet
A
Batur
Yucel
Y
D000208:Acute Disease; D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D007211:Indoles; D007213:Indomethacin / Q000494:pharmacology; D020024:Leukotriene Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D009336:Necrosis; D010179:Pancreas / Q000187:drug effects / Q000473:pathology; D010195:Pancreatitis / Q000188:drug therapy*; D009195:Peroxidase / Q000378:metabolism; D048448:Phenylcarbamates; D011453:Prostaglandins / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides; D014105:Tosyl Compounds / Q000009:adverse effects / Q000627:therapeutic use*
D016861:Cyclooxygenase Inhibitors; D007211:Indoles; D020024:Leukotriene Antagonists; D048448:Phenylcarbamates; D011453:Prostaglandins; D013449:Sulfonamides; D014105:Tosyl Compounds; D009195:Peroxidase; D007213:Indomethacin; C062735:zafirlukast