4-Hydroxydocosahexaenoic acid, a potent peroxisome proliferator-activated receptor gamma agonist alleviates the symptoms of DSS-induced colitis.

Abstract

(5E,7Z,10Z,13Z,16Z,19Z)-4-Hydroxy-5,7,10,13,16,19-docosahexaenoic acid (4-OHDHA) is a potential agonist of peroxisome proliferator-activated receptor-gamma (PPARgamma) and antidiabetic agent as has been previously reported. As PPARgamma agonists may also have anti-inflammatory functions, in this study, we investigated whether 4-OHDHA has an inhibitory effect on expression of inflammatory genes in vitro and whether 4-OHDHA could relieve the symptoms of dextran sodium sulfate (DSS)-induced colitis in a murine model of inflammatory bowel disease. 4-OHDHA inhibited production of nitric oxide and expression of a subset of inflammatory genes including inducible nitric oxide synthase (Nos2/iNOS) and interleukin 6 (Il6) by lipopolysaccharide (LPS)-activated macrophages. In addition, 4-OHDHA-treated mice when compared to control mice not receiving treatment recovered better from the weight loss caused by DSS-induced colitis. Changes in disease activity index (DAI) of 4-OHDHA-treated mice were also more favorable than for control mice and were comparable with mice treated with a typical anti-inflammatory-drug, 5-aminosalichylic acid (5-ASA). These results suggest that 4-OHDHA has potentially clinically useful anti-inflammatory effects mediated by suppression of inflammatory gene expression.

• Authors: Keiko Yamamoto, Yuichi Ninomiya, Mioko Iseki, Yutaka Nakachi, Yukiko Kanesaki-Yatsuka, Yu Yamanoue, Toshimasa Itoh, Yasuho Nishii, Nikolai Petrovsky, Yasushi Okazaki
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 367 Issue 3 Pg. 566-72 (Mar 14 2008) ISSN: 1090-2104 [Electronic] United States
• PMID: 18191038 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 4-hydroxy-5,7,10,13,16,19-docosahexaenoic acid
• Anti-Inflammatory Agents
• Fatty Acids, Unsaturated
• Lipopolysaccharides
• PPAR gamma
• RNA, Messenger
• Nitric Oxide
• Dextran Sulfate
• Nitric Oxide Synthase Type II
• Nos2 protein, mouse

Topics

• Animals
• Anti-Inflammatory Agents (therapeutic use)
• Body Weight (drug effects)
• Cell Line
• Colitis (chemically induced, drug therapy)
• Dextran Sulfate
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Fatty Acids, Unsaturated (therapeutic use)
• Gene Expression (drug effects)
• Gene Transfer Techniques
• Lipopolysaccharides (pharmacology)
• Macrophage Activation (drug effects)
• Male
• Mice
• Mice, Inbred C57BL
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase Type II (genetics)
• PPAR gamma (agonists)
• Promoter Regions, Genetic (drug effects)
• RNA, Messenger (metabolism)
• Severity of Illness Index