Mitigation of indomethacin-induced gastrointestinal damages in fat-1 transgenic mice via gate-keeper action of omega-3-polyunsaturated fatty acids
- Authors
- Han, Young-Min; Park, Jong-Min; Kang, Jing X.; Cha, Ji-Young; Lee, Ho-Jae; Jeong, Migeyong; Go, Eun-Jin; Hahm, Ki Baik
- Issue Date
- 23-Sep-2016
- Publisher
- NATURE PUBLISHING GROUP
- Citation
- SCIENTIFIC REPORTS, v.6
- Journal Title
- SCIENTIFIC REPORTS
- Volume
- 6
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/7879
- DOI
- 10.1038/srep33992
- ISSN
- 2045-2322
- 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 omega-3 polyunsaturated fatty acids (PUFAs) relieve inflammation, reduce oxidative stress, and provide cytoprotection, consequent to lipid raft disorganization. Therefore, we hypothesized that omega-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-1 beta and FAS concentrations, and increased heme oxygenase-1 concentration. Our study indicates that the gatekeeper function of omega-3 PUFAs improves GI safety when administered with NSAID.
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