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Publication
Soluble Epoxide Hydrolase Pharmacological Inhibition Ameliorates Experimental
Acute Pancreatitis in Mice.
Authors Bettaieb A, Chahed S, Bachaalany S, Griffey S, Hammock BD, Haj FG
Submitted By Submitted Externally on 11/3/2015
Status Published
Journal Molecular pharmacology
Year 2015
Date Published 8/1/2015
Volume : Pages 88 : 281 - 90
PubMed Reference 25993999
Abstract Acute pancreatitis (AP) is an inflammatory disease, and is one of the most
common gastrointestinal disorders worldwide. Soluble epoxide hydrolase (sEH;
encoded by Ephx2) deficiency and pharmacological inhibition have beneficial
effects in inflammatory diseases. Ephx2 whole-body deficiency mitigates
experimental AP in mice, but the suitability of sEH pharmacological inhibition
for treating AP remains to be determined. We investigated the effects of sEH
pharmacological inhibition on cerulein- and arginine-induced AP using the
selective sEH inhibitor 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl)
urea (TPPU), which was administered before and after induction of pancreatitis.
Serum amylase and lipase levels were lower in TPPU-treated mice compared with
controls. In addition, circulating levels and pancreatic mRNA of the
inflammatory cytokines tumor necrosis factor-a, interleukin Il-1ß, and Il-6 were
reduced in TPPU-treated mice. Moreover, sEH pharmacological inhibition before
and after induction of pancreatitis was associated with decreased cerulein- and
arginine-induced nuclear factor-?B inflammatory response, endoplasmic reticulum
stress, and cell death. sEH pharmacological inhibition before and after
induction of pancreatitis mitigated cerulein- and arginine-induced AP. This work
suggests that sEH pharmacological inhibition may be of therapeutic value in
acute pancreatitis.




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