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.