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

Life Sciences
Sumanta K GoswamiBruce D Hammock

Abstract

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

Citations

Jun 20, 2019·Frontiers in Pharmacology·Cindy B McReynoldsBruce D Hammock
Aug 18, 2020·Proceedings of the National Academy of Sciences of the United States of America·Anna FishbeinDipak Panigrahy
Jan 17, 2019·Proceedings of the National Academy of Sciences of the United States of America·Allison GartungDipak Panigrahy
May 19, 2019·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Nathani MinazSumanta Kumar Goswami

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