Adjunct therapy of n-3 fatty acids to 5-ASA ameliorates inflammatory score and decreases NF-kappa B in rats with TNBS-induced colitis

作者：Mbodji Khaly; Charpentier Cloe; Guerin Charlene; Querec Coraline; Bole Feysot Christine; Aziz Moutaz; Savoye Guillaume; Dechelotte Pierre; Marion Letellier Rachel^*

来源：Journal of Nutritional Biochemistry, 2013, 24(4): 700-705.

DOI：10.1016/j.jnutbio.2012.03.022

• n-3 PUFA
• 5-ASA
• Colitis
• Inflammation

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 E-2 (P<.001) and leukotriene B-4 (P<.001) were significantly inhibited by n-3 PUFA or 5-ASA therapy. 5-ASA also reduces mRNA levels of tumor necrosis factor a (P<.05). n-3 PUFA or 5-ASA significantly inhibits nuclear factor kappa B (NF-kappa B) activation (P<.01 and P<.05, respectively). The dual therapy n-3 PUFA plus 5-ASA also inhibited inflammatory response by lowering NF-kappa B activation (P<.01) or inducing peroxisome proliferator-activated receptor-gamma (PPAR gamma) 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-kappa B activation and to induce PPAR gamma. 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. 2013 Elsevier Inc.

• 出版日期2013-4