@article {Bettaiebmol.114.097501, author = {Ahmed Bettaieb and Samah Chahed and Santana Bachaalany and Stephen Griffey and Bruce D. Hammock and Fawaz G. Haj}, title = {Soluble Epoxide Hydrolase Pharmacological Inhibition Ameliorates Experimental Acute Pancreatitis in Mice}, elocation-id = {mol.114.097501}, year = {2015}, doi = {10.1124/mol.114.097501}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {Background: 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. Results: 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 TNFα, IL-1β and IL-6 was reduced in TPPU-treated mice. Moreover, sEH pharmacological inhibition before and after induction of pancreatitis was associated with decreased cerulein- and arginine-induced NF-κB inflammatory response, endoplasmic reticulum stress and cell death. Conclusion: sEH pharmacological inhibition before and after induction of pancreatitis mitigated cerulein- and arginine-induced AP. General Significance: This work suggests that sEH pharmacological inhibition may be of therapeutic value in acute pancreatitis.}, issn = {0026-895X}, URL = {https://molpharm.aspetjournals.org/content/early/2015/05/20/mol.114.097501}, eprint = {https://molpharm.aspetjournals.org/content/early/2015/05/20/mol.114.097501.full.pdf}, journal = {Molecular Pharmacology} }