title: Eicosapentaenoic acid and docosapentaenoic acid monoglycerides are more potent than docosahexaenoic acid monoglyceride to resolve inflammation in a rheumatoid arthritis model.
abstract: BACKGROUND
  Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease of the joints and bones. Omega-3 (ω3) fatty acid supplementation has been associated with a decreased production of inflammatory cytokines and eicosanoids involved in RA pathogenesis. The aim of this study was to determine the therapeutic potential of ω3 monoglyceride (MAG-ω3) compounds in an in vivo rat model of RA induced by Complete Freund's Adjuvant (CFA).
  
  
  METHODS
  CFA rats were untreated or treated per os with three specific compounds, namely, MAG-docosahexaenoic acid (MAG-DHA), MAG-eicosapentaenoic acid (MAG-EPA) and MAG-docosapentaenoic acid (MAG-DPA). Morphological and histological analyses, as well as pro-inflammatory marker levels were determined following MAG-ω3 treatments.
  
  
  RESULTS
  Morphological and histological analyses revealed that MAG-EPA and MAG-DPA exhibited strong activity in reducing the progression and severity of arthritic disease in CFA rats. Following MAG-EPA and MAG-DPA treatments, plasma levels of the pro-inflammatory cytokines; interleukin 17A (IL-17A), IL-1β, IL-6 and tumor necrosis factor α (TNFα) were markedly lower when compared to CFA-untreated rats. Results also revealed a decreased activation of p38 mitogen-activated protein kinases (p38 MAPK) and nuclear factor-kappa B (NFκB) pathways correlated with a reduced expression of TNFα, cyclooxygenase-2 (COX-2), matrix metalloproteinase-2 (MMP-2) and MMP-9 in paw homogenates derived from MAG-EPA and MAG-DPA-treated rats. Of interest, the combined treatment of MAG-EPA and vitamin E displayed an antagonistic effect on anti-inflammatory properties of MAG-EPA in CFA rats.
  
  
  CONCLUSIONS
  Altogether, the present data suggest that MAG-EPA, without vitamin E, represents a new potential therapeutic strategy for resolving inflammation in arthritis.
authors.affiliation: SCF Pharma, 235, route du Fleuve Ouest, Ste-Luce, QC, G0K 1P0, Canada. cmorin@scfpharma.com.|Department of Pharmacology-Physiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada. cmorin@scfpharma.com.
authors.forename: Caroline
authors.initials: C
authors.lastname: Morin
authors.affiliation: Department of Biology, Université du Québec à Rimouski, Rimouski, QC, Canada. pierre.blier@uqar.ca.
authors.forename: Pierre U
authors.initials: PU
authors.lastname: Blier
authors.affiliation: SCF Pharma, 235, route du Fleuve Ouest, Ste-Luce, QC, G0K 1P0, Canada. sfortin@scfpharma.com.|Department of Biology, Université du Québec à Rimouski, Rimouski, QC, Canada. sfortin@scfpharma.com.
authors.forename: Samuel
authors.initials: S
authors.lastname: Fortin
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy / Q000378:metabolism; D015153:Blotting, Western; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005260:Female; D007249:Inflammation / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D020381:Interleukin-17 / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D050178:Monoglycerides / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism; D011917:Rats, Inbred Lew; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D005231:Fatty Acids, Unsaturated; D020381:Interleukin-17; D053583:Interleukin-1beta; D015850:Interleukin-6; D050178:Monoglycerides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; D051546:Cyclooxygenase 2; D048051:p38 Mitogen-Activated Protein Kinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C026219:docosapentaenoic acid