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Research ArticleArticle

Soluble Epoxide Hydrolase Pharmacological Inhibition Ameliorates Experimental Acute Pancreatitis in Mice

Ahmed Bettaieb, Samah Chahed, Santana Bachaalany, Stephen Griffey, Bruce D. Hammock and Fawaz G. Haj
Molecular Pharmacology August 2015, 88 (2) 281-290; DOI: https://doi.org/10.1124/mol.114.097501
Ahmed Bettaieb
Departments of Nutrition (A.B., S.C., S.B., F.G.H.) and Entomology and Nematology (B.D.H.), and Comparative Pathology Laboratory (S.G.), University of California Davis, Davis, California; and Department of Internal Medicine (F.G.H.) and Comprehensive Cancer Center (B.D.H., F.G.H.), University of California Davis, Sacramento, California
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Samah Chahed
Departments of Nutrition (A.B., S.C., S.B., F.G.H.) and Entomology and Nematology (B.D.H.), and Comparative Pathology Laboratory (S.G.), University of California Davis, Davis, California; and Department of Internal Medicine (F.G.H.) and Comprehensive Cancer Center (B.D.H., F.G.H.), University of California Davis, Sacramento, California
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Santana Bachaalany
Departments of Nutrition (A.B., S.C., S.B., F.G.H.) and Entomology and Nematology (B.D.H.), and Comparative Pathology Laboratory (S.G.), University of California Davis, Davis, California; and Department of Internal Medicine (F.G.H.) and Comprehensive Cancer Center (B.D.H., F.G.H.), University of California Davis, Sacramento, California
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Stephen Griffey
Departments of Nutrition (A.B., S.C., S.B., F.G.H.) and Entomology and Nematology (B.D.H.), and Comparative Pathology Laboratory (S.G.), University of California Davis, Davis, California; and Department of Internal Medicine (F.G.H.) and Comprehensive Cancer Center (B.D.H., F.G.H.), University of California Davis, Sacramento, California
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Bruce D. Hammock
Departments of Nutrition (A.B., S.C., S.B., F.G.H.) and Entomology and Nematology (B.D.H.), and Comparative Pathology Laboratory (S.G.), University of California Davis, Davis, California; and Department of Internal Medicine (F.G.H.) and Comprehensive Cancer Center (B.D.H., F.G.H.), University of California Davis, Sacramento, California
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Fawaz G. Haj
Departments of Nutrition (A.B., S.C., S.B., F.G.H.) and Entomology and Nematology (B.D.H.), and Comparative Pathology Laboratory (S.G.), University of California Davis, Davis, California; and Department of Internal Medicine (F.G.H.) and Comprehensive Cancer Center (B.D.H., F.G.H.), University of California Davis, Sacramento, California
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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-α, interleukin Il-1β, 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-κB 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.

Footnotes

    • Received December 18, 2014.
    • Accepted May 20, 2015.
  • This work was supported by the National Institutes of Health [Grants R56-DK084317, R01-DK090492, R01-DK095359, K99-DK100736] and the Superfund Basic Research Program from National Institutes of Health National Institute of Environmental Health Sciences [Grant P42-ES04699].

  • dx.doi.org/10.1124/mol.114.097501.

  • Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 88 (2)
Molecular Pharmacology
Vol. 88, Issue 2
1 Aug 2015
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Research ArticleArticle

sEH Pharmacological Inhibition and Acute Pancreatitis

Ahmed Bettaieb, Samah Chahed, Santana Bachaalany, Stephen Griffey, Bruce D. Hammock and Fawaz G. Haj
Molecular Pharmacology August 1, 2015, 88 (2) 281-290; DOI: https://doi.org/10.1124/mol.114.097501

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Research ArticleArticle

sEH Pharmacological Inhibition and Acute Pancreatitis

Ahmed Bettaieb, Samah Chahed, Santana Bachaalany, Stephen Griffey, Bruce D. Hammock and Fawaz G. Haj
Molecular Pharmacology August 1, 2015, 88 (2) 281-290; DOI: https://doi.org/10.1124/mol.114.097501
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