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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.
AuthorsKhaly Mbodji, Cloé Charpentier, Charlène Guérin, Coraline Querec, Christine Bole-Feysot, Moutaz Aziz, Guillaume Savoye, Pierre Déchelotte, Rachel Marion-Letellier
JournalThe Journal of nutritional biochemistry (J Nutr Biochem) Vol. 24 Issue 4 Pg. 700-5 (Apr 2013) ISSN: 1873-4847 [Electronic] United States
PMID22841543 (Publication Type: Journal Article)
CopyrightCopyright © 2013 Elsevier Inc. All rights reserved.
Chemical References
  • Fatty Acids, Omega-3
  • NF-kappa B
  • PPAR gamma
  • Mesalamine
  • Trinitrobenzenesulfonic Acid
Topics
  • Animals
  • Colitis (chemically induced, drug therapy, metabolism)
  • Fatty Acids, Omega-3 (therapeutic use)
  • Inflammation (drug therapy, metabolism)
  • Male
  • Mesalamine (therapeutic use)
  • NF-kappa B (metabolism)
  • PPAR gamma (metabolism)
  • Rats
  • Rats, Sprague-Dawley
  • Trinitrobenzenesulfonic Acid (toxicity)

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