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

Sumanta Kumar Goswami, Amelia Ann Rand, Debin Wan, Jun Yang, Bora Inceoglu, Melany Thomas, Christophe Morisseau, Guang Yu Yang, Bruce D. Hammock

Research output: Contribution to journalArticle

9 Citations (Scopus)

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 100 mg/kg of DCF. Once an ulcerative dose of DCF was chosen, mice were pretreated with TPPU for 7 days at 0.1 mg/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 100 mg/kg and a time post dose of 6 h. 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.

Original languageEnglish (US)
Pages (from-to)114-122
Number of pages9
JournalLife Sciences
Volume180
DOIs
StatePublished - Jul 1 2017

Fingerprint

Epoxide Hydrolases
Diclofenac
Stomach Ulcer
Pharmacology
Stomach
Ulcer
Non-Steroidal Anti-Inflammatory Agents
Apoptosis
Interleukin-6
Gene Knockout Techniques
Omeprazole
Serum
Knockout Mice
Anatomy
Genes
Research

Keywords

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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Goswami, S. K., Rand, A. A., Wan, D., Yang, J., Inceoglu, B., Thomas, M., ... Hammock, B. D. (2017). Pharmacological inhibition of soluble epoxide hydrolase or genetic deletion reduces diclofenac-induced gastric ulcers. Life Sciences, 180, 114-122. https://doi.org/10.1016/j.lfs.2017.05.018

Pharmacological inhibition of soluble epoxide hydrolase or genetic deletion reduces diclofenac-induced gastric ulcers. / Goswami, Sumanta Kumar; Rand, Amelia Ann; Wan, Debin; Yang, Jun; Inceoglu, Bora; Thomas, Melany; Morisseau, Christophe; Yang, Guang Yu; Hammock, Bruce D.

In: Life Sciences, Vol. 180, 01.07.2017, p. 114-122.

Research output: Contribution to journalArticle

Goswami, SK, Rand, AA, Wan, D, Yang, J, Inceoglu, B, Thomas, M, Morisseau, C, Yang, GY & Hammock, BD 2017, 'Pharmacological inhibition of soluble epoxide hydrolase or genetic deletion reduces diclofenac-induced gastric ulcers', Life Sciences, vol. 180, pp. 114-122. https://doi.org/10.1016/j.lfs.2017.05.018
Goswami, Sumanta Kumar ; Rand, Amelia Ann ; Wan, Debin ; Yang, Jun ; Inceoglu, Bora ; Thomas, Melany ; Morisseau, Christophe ; Yang, Guang Yu ; Hammock, Bruce D. / Pharmacological inhibition of soluble epoxide hydrolase or genetic deletion reduces diclofenac-induced gastric ulcers. In: Life Sciences. 2017 ; Vol. 180. pp. 114-122.
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