Effects of dual inhibitor of cyclooxygenase and 5-lipoxygenase on acute necrotizing pancreatitis in rats.
OBJECTIVE
The aim of this study was to investigate the influence of dual inhibitor of cyclooxygenase and 5-lipoxygenase (ER-34122) on acute necrotizing pancreatitis (ANP) induced by glycodeoxycholic acid in rats.


METHODS
ANP was induced in 96 rats by standardized intraductal glycodeoxycholic acid infusion and intravenous cerulein infusion. Rats were divided into six groups (6 rats in each group): Sham + saline, sham + ER-34122, which was dissolved in hydroxypropylmetylcellulose (TC-5RW), sham + TC-5RW, ANP + saline, ANP + ER-34122 and ANP + TC-5RW. Six hours after ANP induction ER-34122 (30 mg/kg), saline or TC-5RW was given by feeding tube. At the 12th hour, routine cardio-respirator, renal parameters were monitored to assess organ function. Serum amylase, alanine amino transferase (ALT), interleukin 6 (IL-6), lactate dehydrogenase (LDH) in bronchoalveolar lavage (BAL) fluid, serum concentration of urea, tissue activity of myeloperoxidase (MPO) and malondialdehyde (MDA) in pancreas and lung were measured. Pancreas histology was examined. In the second part of the study 60 rats were studied in four groups similar to first part. Survival of all rats was monitored for 24 hours.


RESULTS
The induction of ANP resulted in significant increase in mortality rate, pancreatic necrosis and serum activity of amylase, ALT, IL-6, LDH in BAL fluid, serum concentration of urea, tissue activity of MPO and MDA in pancreas and lung, and significant decrease of serum concentrations of calcium, blood pressure, urine output and pO2. NAC did not change serum activity of amylase. The use of ER-34122 inhibited the changes in blood pressure, pO2, serum activity of ALT, pancreatic MPO and MDA levels, partially urine output, LDH level in BAL fluid and pancreatic damage. But ER-34122 could not effect the changes, such as serum activity of amylase, IL-6, serum concentration of urea and calcium, MPO and MDA levels in lung and the mortality rate.


CONCLUSIONS
The use of ER-34122 has a limited value on the course of ANP. It has no role in the treatment of ANP.
Kalyoncu
Nuri I
NI
Department of Pharmacology, Karadeniz Technical University, Trabzon, Turkey.
Alhan
Etem
E
Ercin
Cengiz
C
Kural
Birgul Vanizor
BV
D000818:Animals; D001549:Benzamides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006002:Glycodeoxycholic Acid / Q000494:pharmacology; D015850:Interleukin-6 / Q000097:blood; D007677:Kidney Function Tests; D008084:Lipoxygenase / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000201:enzymology; D008297:Male; D009102:Multiple Organ Failure / Q000188:drug therapy; D010179:Pancreas / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D019283:Pancreatitis, Acute Necrotizing / Q000139:chemically induced / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome
C116824:5-((1,5-bis(4-methoxyphenyl)pyrazol-3-yl)dimethoxymethyl)-2-chlorobenzamide; D001549:Benzamides; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D015850:Interleukin-6; D011720:Pyrazoles; D006002:Glycodeoxycholic Acid; D008084:Lipoxygenase