An α-Linolenic Acid-Rich Formula Reduces Oxidative Stress and Inflammation by Regulating NF-κB in Rats with TNBS-Induced Colitis

We have previously shown that a-linolenic acid (ALA), a (n-3) PUFA exerts in vitro antiinflammatory effects in the intestine. In this study, we aimed to evaluate its effect on inflammatory and oxidative stress in a colitis model. Colitis was induced in 2 groups at d 0 by intrarectal injection of 2-4-6-trinitrobenzen sulfonic acid (TNBS), whereas the control group received the vehicle. Rats we fed 450 mg.kg(-1).d(-1) of ALA (TNBS+ALA) while the other oolitic group (TNBS) and the control group were fed an isocaloric corn oil formula for 14 d (from d -7 to d 7). RBC fatty acid composition was assessed. Oxidative stress was studied by measuring urinary 8-isoprostanes (8-IP) and colon glutathione (GSH) concentration and inducible nitric oxide synthase (iNOS) expression. Colitis was assessed histologically, by production of proinflammatory mediators, including cytokines, leukotrienes B-4 (LTB4), and cyclooxygenase-2 (COX-2) and by nuclear factor-kappa B (NF-kappa B) activation. The ALA-rich diet significantly increased the R BC levels of ALA, eicosapentaenoic acid, and docosapentaenoic acid (n-3) compared with the TNBS group (P < 0.01 for all). The beneficial effect of ALA supplementation on oxidative stress was reflected by lower urinary 8-IP levels (P < 0.05), a normalized colon GSH concentration (P < 0.01), and reduced colon iNOS expression (P < 0.05) compared with the TNBS group. ALA also protected against colon inflammation as assessed by lower tumor necrosis factor-a secretion and mRNA level (P < 0.05), reduced NF-kappa B activation (P = 0.01), and lower colon lipid mediator concentrations such as LTB4 and COX-2 (P < 0.05) compared with the TNBS group. These findings show that an ALA-rich formula is beneficial to TNBS-induced oolitic rats via inhibition of oxidative and inflammatory stress. J. Nutr. 140: 1714-1721, 2010.