Resolution of Cox mediated inflammation by Se supplementation in mouse experimental model of colitis

PLoS One. 2018 Jul 31;13(7):e0201356. doi: 10.1371/journal.pone.0201356. eCollection 2018.

Abstract

UC a form of IBD is a chronic inflammatory disorder of large intestine, with unknown etiology. Reports suggest a critical role of COX-2 dependent prostaglandins (PGs) mediated inflammatory pathway in pathophysiology of UC. However, COX inhibition using NSAIDs exacerbate IBD and thus is not a viable solution. Currently, in DSS induced experimental colitis in mice, we have demonstrated that dietary Se supplementation (0.5ppm as sodium selenite) symptomatically resolves the signs of inflammation in a redox sensitive manner as compared to Se deficient (0.01ppm) conditions, as seen by modulation in oxidative stress markers, morphological changes, histopathological examinations, biochemical studies such as MPO activity, activity of intestinal markers enzymes as well as mRNA and expressions of various pro and anti-inflammatory factors such as, mPGES, hPGDS, TXAS, 15-PGDH, GPX-1 and GPX-2. These findings were validated and correlated with changes in the biophysical parameters such as membrane fluidity, electrical parameters (impedance), transport across the colonic tissue and FTIR. Current study not only concluded that Se at supranutritional concentrations by modulating the redox status relieves the signs of colitis by regulating COX dependent PG biosynthetic pathway, but also sheds light on the biophysical characterization of these inflammatory/resolution pathways involved in UC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Cyclooxygenase 2 / metabolism*
  • Dietary Supplements*
  • Disease Models, Animal
  • Gene Expression Regulation / drug effects*
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Inflammation / pathology
  • Inflammatory Bowel Diseases / drug therapy
  • Inflammatory Bowel Diseases / metabolism*
  • Inflammatory Bowel Diseases / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Selenium / pharmacology
  • Signal Transduction / drug effects*
  • Sodium Selenite / pharmacology*

Substances

  • Biomarkers
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • Selenium
  • Sodium Selenite

Grants and funding

This work was supported by Science and Engineering Research Board, (SERB/F/5080/2-15-16), Govt of India; University Grants Commission (IN), UGC (F. 30-86/2014 (BSR)), Govt of India, New Delhi. The assistance to Panjab University and Department of Biophysics through programs like DST- PURSE and DST-FIST & UGC-SAP respectively are also duly acknowledged. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.