title: Adjunct therapy of n-3 fatty acids to 5-ASA ameliorates inflammatory score and decreases NF-κB in rats with TNBS-induced colitis.
abstract: 5-aminosalicylic acid (5-ASA) is widely used for the treatment of inflammatory bowel disease (IBD). Recent studies have evaluated the potential of nutritional intervention as adjunct therapy to 5-ASA in IBD. N-3 polyunsaturated fatty acids (PUFA) have shown potent anti-inflammatory properties in gut inflammation. Therefore, we aimed to evaluate the efficacy of the dual therapy (n-3 PUFA plus 5-ASA) in rats with 2, 4, 6-trinitrobenzen sulfonic acid (TNBS)-induced colitis. Colitis was induced by intrarectal injection of TNBS while control rats received the vehicle. Rats received by gavage a fish oil-rich formula (n-3 groups) or an isocaloric and isolipidic oil formula supplemented with 5-ASA for 14 days. A dose response of 5-ASA (5-75 mg. suppression mg kg(-1) d(-1)) was tested. Colitis was evaluated and several inflammatory markers were quantified in the colon. COX-2 expression (P<.05) and pro-inflammatory eicosanoids production of prostaglandin E2 (P<.001) and leukotriene B4 (P<.001) were significantly inhibited by n-3 PUFA or 5-ASA therapy. 5-ASA also reduces mRNA levels of tumor necrosis factor α (P<.05). n-3 PUFA or 5-ASA significantly inhibits nuclear factor κB (NF-κB) activation (P<.01 and P<.05, respectively). The dual therapy n-3 PUFA plus 5-ASA also inhibited inflammatory response by lowering NF-κB activation (P<.01) or inducing peroxisome proliferator-activated receptor-γ (PPARγ) expression (P<.05). These results indicate that 5-ASA plus n-3 PUFAs are more effective than a higher dose of 5-ASA alone to reduce NF-κB activation and to induce PPARγ. By contrast, the dual therapy did not improve the effects of individual treatments on eicosanoids or cytokine production. Use of n-3 PUFA in addition to 5-ASA may reduce dose of standard therapy.
authors: Appareil Digestif Environnement Nutrition (ADEN EA 4311), Medicine University, IFR 23, Institute of Biomedical Research, Rouen, France.
authors: Khaly
authors: K
authors: Mbodji
authors: Cloé
authors: C
authors: Charpentier
authors: Charlène
authors: C
authors: Guérin
authors: Coraline
authors: C
authors: Querec
authors: Christine
authors: C
authors: Bole-Feysot
authors: Moutaz
authors: M
authors: Aziz
authors: Guillaume
authors: G
authors: Savoye
authors: Pierre
authors: P
authors: Déchelotte
authors: Rachel
authors: R
authors: Marion-Letellier
mesh_terms: D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D019804:Mesalamine / Q000627:therapeutic use*; D016328:NF-kappa B / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity*
chemical_list: D015525:Fatty Acids, Omega-3; D016328:NF-kappa B; D047495:PPAR gamma; D019804:Mesalamine; D014302:Trinitrobenzenesulfonic Acid