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


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-1β, 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 downregulated 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.
Cho
Jae Young
JY
Korea Food Research Institute, Backhyun-dong, Bundang-gu, Sungnam-si, Kyonggi-do, Korea.
Chi
Sung-Gil
SG
Chun
Hyang Sook
HS
D000209:Acute-Phase Proteins / Q000235:genetics / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D001835:Body Weight / Q000187:drug effects; D003092:Colitis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D003106:Colon / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D016264:Dextran Sulfate / Q000633:toxicity; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000627:therapeutic use*; D005786:Gene Expression Regulation / Q000187:drug effects; D018836:Inflammation Mediators / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D007509:Irritants / Q000633:toxicity; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020411:Oligonucleotide Array Sequence Analysis; D009195:Peroxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D012720:Severity of Illness Index; D012460:Sulfasalazine / Q000494:pharmacology / Q000627:therapeutic use
D000209:Acute-Phase Proteins; D000894:Anti-Inflammatory Agents, Non-Steroidal; D018836:Inflammation Mediators; D007509:Irritants; D012333:RNA, Messenger; D004281:Docosahexaenoic Acids; D012460:Sulfasalazine; D016264:Dextran Sulfate; D009195:Peroxidase