title: Oleic acid, hydroxytyrosol and n-3 fatty acids collectively modulate colitis through reduction of oxidative stress and IL-8 synthesis; in vitro and in vivo studies.
abstract: Our recent study has demonstrated that medium chain triglycerides (MCT) and monounsaturated fatty acids potentiate the beneficial effects of fish oil on risk factors of cardiovascular disease. In the present study, we have investigated the influence of MCT or olive oil on the protective and mucosal healing ability of fish oil in ulcerative colitis using cell simulation and animal models. Caco-2 cells grown in medium chain fatty acids enriched medium has exaggerated t-butyl hydroperoxide induced cell damage, GSH depletion, and IL-1β induced IL-8 synthesis, compared to the cells grown in oleic acid & hydroxytyrosol (OT) enriched medium. Further, combined treatment of cells with eicosapentaenoic acid, docosahexaenoic acid, and OT has remarkably attenuated the cell damage, and IL-8 synthesis, compared to individual treatments. To evaluate the effect of these lipid formulations in vivo, adult Wistar rats were fed diet enriched with high amount of medium chain triglycerides (MCT), virgin olive oil, or their combination with fish oil. Colitis was induced in rats using dextran sulfate sodium (DSS) for 7days followed by 10-days of recovery period. Rats of MCT group exhibit severe disease activity, higher levels of inflammatory cytokines in the colon compared to the olive oil group. Furthermore, there was persistent body weight loss, loose stools, higher levels of inflammatory cytokines in the rats of MCT group, even after DSS was withdrawn from drinking water. Conversely, fish oil has remarkably attenuated the DSS induced alterations in both MCT and olive oil diet groups with significantly greater effect in the olive oil group. Thus, MCT increase the susceptibility to colitis through oxidative damage and IL-8 synthesis in intestinal epithelial cells. The beneficial effects of virgin olive oil could be partially attributed to hydroxytyrosol. Combined treatment of hydroxytyrosol, oleic acid and n-3 fatty acids exhibit huge therapeutic benefits in colitis.
authors.affiliation: Department of Biochemistry and Nutrition, CSIR-Central Food Technological Research Institute, Mysore 570020, India.
authors.forename: K Vijay Kumar
authors.initials: KVK
authors.lastname: Reddy
authors.affiliation: Department of Biochemistry and Nutrition, CSIR-Central Food Technological Research Institute, Mysore 570020, India. Electronic address: aknaidu@cftri.res.in.
authors.forename: K Akhilender
authors.initials: KA
authors.lastname: Naidu
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000188:drug therapy*; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use*; D005395:Fish Oils / Q000627:therapeutic use*; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D008297:Male; D019301:Oleic Acid / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar
chemical_list: D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D016209:Interleukin-8; C005975:3,4-dihydroxyphenylethanol; D019301:Oleic Acid; D016264:Dextran Sulfate; D010626:Phenylethyl Alcohol
keywords: Docosahexaenoic acid; Eicosapentaenoic acid; Fish oil; Hydroxytyrosol; Inflammatory cytokines; Medium chain triglycerides; Mucosal healing; Ulcerative colitis