title: Telmisartan treatment targets inflammatory cytokines to suppress the pathogenesis of acute colitis induced by dextran sulphate sodium.
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 5mg/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.
authors: Department of Clinical Pharmacology, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956 8603, Japan.
authors: Somasundaram
authors: S
authors: Arumugam
authors: Department of Clinical Pharmacology, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956 8603, Japan.
authors: Remya
authors: R
authors: Sreedhar
authors: Department of Clinical Pharmacology, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956 8603, Japan; Department of Cardiovascular Sciences, Houston Methodist Research Institute, Houston, TX 77030, USA.
authors: Rajarajan A
authors: RA
authors: Thandavarayan
authors: J.K.K. Nattraja College of Pharmacy, Natarajapuram, Komarapalayam, Namakkal 638183, Tamil Nadu, India.
authors: Vijayasree V
authors: VV
authors: Giridharan
authors: Department of Clinical Pharmacology, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956 8603, Japan.
authors: Vengadeshprabhu
authors: V
authors: Karuppagounder
authors: Department of Clinical Pharmacology, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956 8603, Japan.
authors: Vigneshwaran
authors: V
authors: Pitchaimani
authors: Department of Clinical Pharmacology, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956 8603, Japan.
authors: Mst Rejina
authors: MR
authors: Afrin
authors: Department of Clinical Pharmacology, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956 8603, Japan.
authors: Shizuka
authors: S
authors: Miyashita
authors: Department of Clinical Pharmacology, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956 8603, Japan.
authors: Mayumi
authors: M
authors: Nomoto
authors: Department of Clinical Pharmacology, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956 8603, Japan.
authors: Meilei
authors: M
authors: Harima
authors: Department of Clinical Pharmacology, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956 8603, Japan.
authors: Hiroshi
authors: H
authors: Suzuki
authors: Department of Clinical Pharmacology, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956 8603, Japan.
authors: Takashi
authors: T
authors: Nakamura
authors: Department of Cardiology, Yamanashi Prefectural Central Hospital, Kofu, Yamanashi, Japan.
authors: Masahiko
authors: M
authors: Nakamura
authors: Department of Gastroenterology and Hepatology, Niigata University of Graduate School of Medical and Dental Sciences, Niigata 951 8510, Japan.
authors: Kenji
authors: K
authors: Suzuki
authors: Department of Clinical Pharmacology, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956 8603, Japan. Electronic address: watanabe@nupals.ac.jp.
authors: Kenichi
authors: K
authors: Watanabe
mesh_terms: D000208:Acute Disease; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D053148:Caspase 3 / Q000276:immunology; D053179:Caspase 7 / Q000276:immunology; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology; D016207:Cytokines / Q000276:immunology*; D016264:Dextran Sulfate / Q000633:toxicity*; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000276:immunology; D000077333:Telmisartan
chemical_list: D001562:Benzimidazoles; D001565:Benzoates; D016207:Cytokines; D019253:Proto-Oncogene Proteins c-bcl-2; C052617:Bcl2 protein, mouse; D016264:Dextran Sulfate; C505409:Casp3 protein, mouse; C505524:Casp7 protein, mouse; D053148:Caspase 3; D053179:Caspase 7; D000077333:Telmisartan
keywords: Acute colitis; Apoptosis; Inflammatory cytokines; Renin angiotensin system; Telmisartan