Journal
LIFE SCIENCES
Volume 180, Issue -, Pages 114-122Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2017.05.018
Keywords
Diclofenac; Soluble epoxide hydrolase inhibitor TPPU; Stomach ulcer; Apoptosis; TNF-alpha; IL-6
Funding
- National Institute of Environmental Health Sciences (NIEHS) [R01 ES002710]
- NIEHS Superfund Research Program [P42 ES004699]
- West Coast Central Comprehensive Metabolomics Center [U24 DK097154]
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) [R21 AR062866]
- National Cancer Institute [R01 CA172431, R01 CA164041]
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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-alpha 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-alpha 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. (C) 2017 Elsevier Inc. All rights reserved.
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