Telmisartan treatment targets inflammatory cytokines to suppress the pathogenesis of acute colitis induced by dextran sulphate sodium

Somasundaram Arumugam, Remya Sreedhar, Rajarajan A. Thandavarayan, Vijayasree V. Giridharan, Vengadeshprabhu Karuppagounder, Vigneshwaran Pitchaimani, Mst Rejina Afrin, Shizuka Miyashita, Mayumi Nomoto, Meilei Harima, Hiroshi Suzuki, Takashi Nakamura, Masahiko Nakamura, Kenji Suzuki, Kenichi Watanabe

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

The renin angiotensin system (RAS) is essential for the regulation of cardiovascular and renal functions to maintain the fluid and electrolyte homeostasis. Recent studies have demonstrated a locally expressed RAS in various tissues of mammals, which is having pathophysiological roles in those organ system. Interestingly, local RAS has important role during the inflammatory bowel disease pathogenesis. Further to delineate its role and also to identify the potential effects of telmisartan, an angiotensin receptor blocker, we have used a mouse model of acute colitis induced by dextran sulphate sodium. We have used 0.01 and 5. mg/kg body weight doses of telmisartan and administered as enema to facilitate the on-site action and to reduce the systemic adverse effects. Telmisartan high dose treatment significantly reduced the disease activity index score when compared with the colitis control mice. In addition, oxidative stress and endoplasmic reticulum stress markers expression were also significantly reduced when compared with the colitis control mice. Subsequent experiments were carried out to investigate some of the mechanisms underlying its anti-inflammatory effects and identified that the mRNA levels of pro-inflammatory cytokines such as tumour necrosis factor α, interleukin 1β, interleukin 6 and monocyte chemoattractant protein 1 as well as cellular DNA damage were significantly suppressed when compared with the colitis control mice. Similarly the apoptosis marker proteins such as cleaved caspase 3 and 7 levels were down-regulated and anti-apoptotic protein Bcl2 level was significantly upregulated by telmisartan treatment. These results indicate that blockade of RAS by telmisartan can be an effective therapeutic option against acute colitis.

Original languageEnglish (US)
Pages (from-to)305-312
Number of pages8
JournalCytokine
Volume74
Issue number2
DOIs
StatePublished - Dec 3 2015

Keywords

  • Acute colitis
  • Apoptosis
  • Inflammatory cytokines
  • Renin angiotensin system
  • Telmisartan

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Biochemistry
  • Hematology
  • Molecular Biology

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