Skip Navigation

Publication Detail

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

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

Published In Life Sci, (2017 Jul 01)

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.

PubMed ID: 28522175 Exiting the NIEHS site

MeSH Terms: Animals; Anti-Inflammatory Agents, Non-Steroidal/administration & dosage; Anti-Inflammatory Agents, Non-Steroidal/toxicity*; Anti-Ulcer Agents/pharmacology; Apoptosis/drug effects; Diclofenac/administration & dosage; Diclofenac/toxicity*; Dose-Response Relationship, Drug; Enzyme Inhibitors/pharmacology; Epoxide Hydrolases/antagonists & inhibitors*; Epoxide Hydrolases/genetics; Gene Deletion; Hydrogen-Ion Concentration; Interleukin-6/blood; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Omeprazole/pharmacology; Phenylurea Compounds/pharmacology*; Piperidines/pharmacology*; Stomach Ulcer/pathology; Stomach Ulcer/prevention & control*; Time Factors; Tumor Necrosis Factor-alpha/blood

Back
to Top