Mitigation of indomethacin-induced gastrointestinal damages in fat-1 transgenic mice via gate-keeper action of ω-3-polyunsaturated fatty acids

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Mitigation of indomethacin-induced gastrointestinal damages in fat-1 transgenic mice via gate-keeper action of ω-3-polyunsaturated fatty acids

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Title: Mitigation of indomethacin-induced gastrointestinal damages in fat-1 transgenic mice via gate-keeper action of ω-3-polyunsaturated fatty acids
Author: Han, Young-Min; Park, Jong-Min; Kang, Jing X.; Cha, Ji-Young; Lee, Ho-Jae; Jeong, Migeyong; Go, Eun-Jin; Hahm, Ki Baik

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Citation: Han, Young-Min, Jong-Min Park, Jing X. Kang, Ji-Young Cha, Ho-Jae Lee, Migeyong Jeong, Eun-Jin Go, and Ki Baik Hahm. 2016. “Mitigation of indomethacin-induced gastrointestinal damages in fat-1 transgenic mice via gate-keeper action of ω-3-polyunsaturated fatty acids.” Scientific Reports 6 (1): 33992. doi:10.1038/srep33992. http://dx.doi.org/10.1038/srep33992.
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Abstract: Non-steroidal anti-inflammatory drugs (NSAIDs) damage the gastrointestinal (GI) epithelial cell membranes by inducing several signals through lipid raft organization after membrane incorporation, whereas ω-3 polyunsaturated fatty acids (PUFAs) relieve inflammation, reduce oxidative stress, and provide cytoprotection, consequent to lipid raft disorganization. Therefore, we hypothesized that ω-3 PUFAs can protect the GI from NSAID-induced damages by initiating the gatekeeper action of cell membranes, subsequent to anti-inflammatory and anti-oxidative actions. Administration of indomethacin (IND) leads to the formation of lipid rafts and activation of caveolin-1; however, no such observations were made upon co-administration of eicosapentaenoic acid (EPA) and IND. In addition, the EPA-induced lipid raft disorganization, caveolin-1 inactivation, and cellular cytotoxicity were inhibited when target cells were knocked-out using G-protein coupled receptor 120 (GPR 120). EPA significantly attenuated IND-induced oxidative damage and apoptosis. IND administration induced significant ulceration, bleeding, and oedema in the stomach or small intestine of wild-type (WT) mice; however, such severe damages to the GI significantly decreased in fat-1 transgenic (TG) mice (P < 0.001), which exhibited decreased cyclooxygenase-2 expression and apoptosis, decreased interleukin-1β and FAS concentrations, and increased heme oxygenase-1 concentration. Our study indicates that the gatekeeper function of ω-3 PUFAs improves GI safety when administered with NSAID.
Published Version: doi:10.1038/srep33992
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5034283/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:29407670
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