Oral administration of docosahexaenoic acid attenuates colitis induced by dextran sulfate sodium in mice

Scope: Dietary supplementation of n-3 PUFAs, containing docosahexaenoic acid (DHA), modulates the symptoms of colitis. Hence, we investigated the effects of oral administration of pure DHA and the therapeutic agent sulfasalazine (SAL) on chemically induced colitis in mice, and analyzed the expression levels of DHA-responsive genes in colonic tissue using cDNA arrays. Methods and results: Colitis in BALB/c mice was induced by feeding 5% dextran sulfate sodium (DSS) in drinking water for 7 days. DHA (30 mg/kg/day, DHA) or SAL (100 mg/kg/ day, SAL) was administered orally throughout the treatment along with DSS. The DHA-treated group showed significant reduction of the weight loss and colon shortening compared to the DSS-treated colitis group. In contrast, SAL treatment was effective in reducing colon shortening, stool consistency and bleeding scores. DHA and SAL treatments also significantly reduced the changes in inflammation of the colon, and reversed the increase in myeloperoxidase activity induced by DSS. Among DSS-responsive genes, those for inflammatory cytokines (IL-1 beta, CD14 antigen and tumor necrosis factor receptor superfamily, member 1b), membrane remodeling genes (matrix metalloproteinase-3, -10 and -13) and acute phase proteins (S100 calcium-binding protein A8), which were increased by DSS, were down-regulated by DHA or SAL treatment. Conclusions: DHA was effective in alleviating DSS-induced colitis in mice, partly by modulating the expression levels of genes involved in colitis.