Telmisartan Attenuates Colon Inflammation, Oxidative Perturbations and Apoptosis in a Rat Model of Experimental Inflammatory Bowel Disease

Abstract

Accumulating evidence has indicated the implication of angiotensin II in the pathogenesis of inflammatory bowel diseases (IBD) via its proinflammatory features. Telmisartan (TLM) is an angiotensin II receptor antagonist with marked anti-inflammatory and antioxidant actions that mediated its cardio-, reno- and hepatoprotective actions. However, its impact on IBD has not been previously explored. Thus, we aimed to investigate the potential alleviating effects of TLM in tri-nitrobenezene sulphonic acid (TNBS)-induced colitis in rats. Pretreatment with TLM (10 mg/kg p.o.) attenuated the severity of colitis as evidenced by decrease of disease activity index (DAI), colon weight/length ratio, macroscopic damage, histopathological findings and leukocyte migration. TLM suppressed the inflammatory response via attenuation of tumor necrosis factor-α (TNF-α), prostaglandin E2 (PGE2) and myeloperoxidase (MPO) activity as a marker of neutrophil infiltration besides restoration of interleukin-10 (IL-10). TLM also suppressed mRNA and protein expression of nuclear factor kappa B (NF-κB) p65 and mRNA of cyclo-oxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) proinflammatory genes with concomitant upregulation of PPAR-γ. The alleviation of TLM to colon injury was also associated with inhibition of oxidative stress as evidenced by suppression of lipid peroxides and nitric oxide (NO) besides boosting glutathione (GSH), total anti-oxidant capacity (TAC) and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx). With respect to apoptosis, TLM downregulated the increased mRNA, protein expression and activity of caspase-3. It also suppressed the elevation of cytochrome c and Bax mRNA besides the upregulation of Bcl-2. Together, these findings highlight evidences for the beneficial effects of TLM in IBD which are mediated through modulation of colonic inflammation, oxidative stress and apoptosis.

Sasa quelpaertensis leaf extract regulates microbial dysbiosis by modulating the composition and diversity of the microbiota in dextran sulfate sodium-induced colitis mice

“…In animal models of IBD, DAI value and colonic length are key indicators for evaluating the severity of colitis [35, 36]. Consistent with the results of a previous study [17], SQE supplementation attenuated the severity of colitis by lowering the DAI value and extending the length of the colon.…”

Wild jujube polysaccharides protect against experimental inflammatory bowel disease by enabling enhanced intestinal barrier function

“…41 However, there is no effect of WJPs on the production of pro-inflammatory cytokines (TNF-α) in the macrophage. In this study, we demonstrated protection against colitis induced by TNBS in rats with WJPs treatment, exhibiting improved DAI scores, colon length, wet weight, histological damage and production of pro-inflammatory cytokines.…”

Protective Effects of Honey and Spirulina Platensis on Acetic Acid-Induced Ulcerative Colitis in Rats

“…This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited Inflammatory cell infiltration (mainly macrophages and neutrophils) during acute inflammation increases the formation of ROS and proinflammatory cytokines, such as TNF-α, IL-6, IL-1β, and inducible nitric oxide synthase (iNOS) (7,8). Overproduction of ROS, NO, and PGE2 leads to increased lipid peroxidation, decreased intestinal epithelial barrier integrity, and ultimately mucosal disruption and ulceration (9,10). Many immunogenic bacterial antigens from the damaged epithelial barrier enter submucosal layers and start a ruinous cascade of immune responses (11).…”