Dietary α-linolenic acid�rich formula reduces adhesion molecules in rats with experimental colitis

Objective: The omega 3 polyunsaturated fatty acid therapy in inflammatory bowel disease is focused on the effects on fish oil derived polyunsaturated fatty acids. We speculated that a vegetal oil rich in alpha linolenic acid (ALA) might also inhibit colitis. Therefore, we evaluated whether dietary ALA would decrease the expression of adhesion molecules by inducing the protective enzyme heme oxygenase 1 (HO1) in a rat colitis model. Methods: Colitis was induced at day 0 by an intrarectal injection of 2 4 6 trinitrobenzen sulfonic acid (TNBS), whereas control rats received the vehicle. Rats were fed an ALA rich formula 450 mg per kg per day, whereas the other colitic group (TNBS) and the control group were fed an isocaloric corn oil formula for 14 d (from day minus 7 to day 7). The colonic expressions of intercellular adhesion molecule1 (ICAM1), vascular cell adhesion molecule 1 (VCAM1), vascular endothelial growth factor A receptor 2 (VEGFR2), and HO1 were studied by immunohistochemistry. Results: The ALA rich diet significantly decreased the expression of ICAM1, VCAM1, and VEGFR2 compared the TNBS group, but it did not affect the expression of HO1. Conclusion: A vegetal ALA rich formula decreases the expression of ICAM1, VCAM1, and VEGFR2 and independently of HO1 in rats with TNBS induced colitis. Further studies are required to evaluate its therapeutic potential in inflammatory bowel disease as an alternative to fish oil. (Authors abstract)

Inflammatory bowel diseases (IBDs), such as ulcerative colitis and Crohn�s disease, are chronic inflammatory disorders mediated by the expression of adhesion molecules on endothelial and inflammatory cells. Adhesion molecules such as intercellular adhesion molecule1 (ICAM1) or vascular cell adhesion molecule1 (VCAM1) are up regulated in the intestinal mucosa of patients with IBD and in experimental colitis. Alpha linolenic acid (ALA) has been shown to down regulate interleukin (IL)1 induced cytokine production in enterocytelike Caco2 cells but is less potent than DHA and EPA. In rats with 2-4-6- trinitrobenzen sulfonic acid (TNBS) induced colitis, a dietary ALA rich formula improved colitis by decreasing inflammation and oxidative stress. The present study aimed to evaluate whether a dietary ALA rich formula can down regulate adhesion molecules and VEGFR2 in an experimental model of IBD. An up regulation of the adhesion molecules VCAM1 and ICAM1 in colitis was noted which was alleviated by the dietary ALA rich formula. In dyslipidemic patients, supplementation with ALA for 12 wk has also been found to lead to a decrease of blood-soluble VCAM1. In the present study, an increased immunostaining of VEGFR2 in colitic rats that was down regulated by the dietary ALA rich formula was observed. The ability of the dietary ALA rich formula to down regulate cyclooxygenase-2 may explain its inhibitory role on angiogenesis in colitic rats. It has been shown that DHA activated PPARg in enterocyte like Caco2 cells, whereas ALA did not. This may explain the lack of effect of ALA on HO1. Because a dietary ALA rich formula has been found to inhibit nuclear factor kB activation that mediates the gene expression of adhesion molecules, the authors speculate that down regulation of adhesion molecules by a dietary ALA rich formula would be mediated through this pathway. A potential mechanism behind the inhibitory effect of an ALA rich formula on adhesion molecules may be mediated through the inhibition of tumor necrosis factor-a, a key cytokine in intestinal inflammation. The authors suggest further studies to evaluate the therapeutic potential of ALA in IBD as an alternative to fish oil (Editors comments).