Khaly Mbodji, Cloé Charpentier, Charlène Guérin, Coraline Querec, Christine Bole-Feysot, Moutaz Aziz, Guillaume Savoye, Pierre Déchelotte, Rachel Marion-Letellier

Journal of Nutritional Biochemistry 24 (2013) 700–705 

PMID: 22841543

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 (Pb.05) and pro-inflammatory eicosanoids production of prostaglandin E2 (Pb.001) and leukotriene B4 (Pb.001) were significantly inhibited by n-3 PUFA or 5-ASA therapy. 5-ASA also reduces mRNA levels of tumor necrosis factor α (Pb.05). n-3 PUFA or 5-ASA significantly inhibits nuclear factor κB (NF-κB) activation (Pb.01 and Pb.05, respectively). The dual therapy n-3 PUFA plus 5-ASA also inhibited inflammatory response by lowering NF-κB activation (Pb.01) or inducing peroxisome proliferator-activated receptor-γ (PPARγ) expression (Pb.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.