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Life Sci. 2017 Jul 1;180:114-122. doi: 10.1016/j.lfs.2017.05.018. Epub 2017 May 15.

Pharmacological inhibition of soluble epoxide hydrolase or genetic deletion reduces diclofenac-induced gastric ulcers.

Author information

1
Department of Entomology and Nematology, and Comprehensive Cancer Center, University of California, Davis, CA 95616, USA.
2
Department of Pathology, Feinberg School of Medicine, Northwestern University, 303 East Chicago Avenue, Chicago, IL 60611, USA.
3
Department of Entomology and Nematology, and Comprehensive Cancer Center, University of California, Davis, CA 95616, USA. Electronic address: bdhammock@ucdavis.edu.

Abstract

AIMS:

This research was conducted to evaluate the hypothesis that gastric ulcers caused by the NSAID diclofenac sodium (DCF) can be prevented by the soluble epoxide hydrolase inhibitor TPPU.

MAIN METHODS:

Mice were administered a single dose of 10, 30 or 100mg/kg of DCF. Once an ulcerative dose of DCF was chosen, mice were pretreated with TPPU for 7days at 0.1mg/kg to evaluate anti-ulcer effects of the sEH inhibitor on anatomy, histopathology, pH, inflammatory markers and epithelial apoptosis of stomachs.

KEY FINDINGS:

Diclofenac caused ulceration of the stomach at a dose of 100mg/kg and a time post dose of 6h. Ulcers generated under these conditions were associated with a significant increase in the levels of TNF-α and IL-6 in serum and increased apoptosis compared to control mice. Pretreatment with TPPU resulted in a decrease of ulceration in mice treated with DCF with a significant decrease in the level of apoptosis, TNF-α and IL-6 in the serum in comparison to diclofenac-treated mice. TPPU did not affect the pH of the stomach, whereas omeprazole elevated the pH of the stomach as expected. A similar anti-ulcer effect was observed in sEH gene knockout mice treated with DCF.

SIGNIFICANCE:

The sEH inhibitor TPPU decreases the NSAID-induced stomach ulcers.

KEYWORDS:

Apoptosis; Diclofenac; IL-6; Soluble epoxide hydrolase inhibitor TPPU; Stomach ulcer; TNF-α

PMID:
28522175
PMCID:
PMC5659729
DOI:
10.1016/j.lfs.2017.05.018
[Indexed for MEDLINE]
Free PMC Article

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