MAG-EPA reduces severity of DSS-induced colitis in rats

Am J Physiol Gastrointest Liver Physiol. 2016 May 15;310(10):G808-21. doi: 10.1152/ajpgi.00136.2015. Epub 2016 Mar 24.

Abstract

Ulcerative colitis (UC) is a chronic disease characterized by diffuse inflammation of the intestinal mucosa of the large bowel. Omega-3 (ω3) fatty acid supplementation has been associated with a decreased production of inflammatory cytokines involved in UC pathogenesis. The aim of this study was to determine the preventive and therapeutic potential of eicosapentaenoic acid monoglyceride (MAG-EPA) in an in vivo rats model of UC induced by dextran sulfate sodium (DSS). DSS rats were untreated or treated per os with MAG-EPA. Morphological, histological, and biochemical analyses were performed following MAG-EPA administrations. Morphological and histological analyses revealed that MAG-EPA pretreatment (12 days pre-DSS) and treatment (6 days post-DSS) exhibited strong activity in reducing severity of disease in DSS rats. Following MAG-EPA administrations, tissue levels of the proinflammatory cytokines TNF-α, IL-1β, and IL-6 were markedly lower compared with rats treated only with DSS. MAG-EPA per os administration decrease neutrophil infiltration in colon tissues, as depicted by myelohyperoxidase activity. Results also revealed a reduced activation of NF-κB pathways correlated with a decreased expression of COX-2 in colon homogenates derived from MAG-EPA-pretreated and treated rats. Tension measurements performed on colon tissues revealed that contractile responses to methacholine and relaxing effect induced by sodium nitroprusside were largely increased following MAG-EPA treatment. The combined treatment of MAG-EPA and vitamin E displayed an antagonistic effect on anti-inflammatory properties of MAG-EPA in DSS rats.

Keywords: TNF-α; colitis; eicosapentaenoic acid; inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Colitis, Ulcerative / drug therapy*
  • Colitis, Ulcerative / etiology
  • Colitis, Ulcerative / prevention & control
  • Cyclooxygenase 2 / metabolism
  • Dextran Sulfate / toxicity
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / metabolism
  • Monoglycerides / administration & dosage
  • Monoglycerides / pharmacology
  • Monoglycerides / therapeutic use*
  • NF-kappa B / metabolism
  • Rats
  • Rats, Wistar
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • 1-eicosapentaenoylglycerol
  • Interleukin-1beta
  • Interleukin-6
  • Monoglycerides
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • Dextran Sulfate
  • Cyclooxygenase 2