ACE inhibitors and angiotensin II receptor antagonists in Crohn’s disease management

Hume, Georgia; Radford‐Smith, Graham

doi:10.1586/17474124.2.5.645

Cited by 18 publications

(26 citation statements)

References 60 publications

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“…These findings are consistent with previous reports [3], [10], [43], [44]. Ang II has been previously reported to increase the generation of TNF-α probably via activation of NF-κB [8]. TNF-α is a pleiotropic cytokine which has been implicated in IBD pathogenesis via activation of immune cells, generation of other proinflammatory cytokines and overexpression of angiotensinogen and Ang II [2], [8].…”

Section: Discussionsupporting

confidence: 92%

“…Besides its classical role in the regulation of blood pressure and fluid homoeostasis, novel activities of RAS have been identified including immune cell modulation with proinflammatory actions [8]. RAS has been implicated in the pathogenesis of IBD via upregulation of Ang II AT1 receptors throughout the colon [1], [8].…”

Section: Discussionmentioning

confidence: 99%

“…RAS has been implicated in the pathogenesis of IBD via upregulation of Ang II AT1 receptors throughout the colon [1], [8]. Ang II is involved in several key steps of the inflammatory cascade that ultimately provoke intestinal injury and ulceration including polymorphonuclear leukocyte (PMN) infiltration, probably, via upregulation of adhesion molecules [8], [42].…”

Section: Discussionmentioning

confidence: 99%

“…Angiotensin II (Ang II), the main effector peptide of the rennin-angiotensin system (RAS), has potent proinflammatory features linked with the pathogenesis of several chronic inflammatory disorders including IBD [8]. Via its actions on angiotensin II type 1 (AT1) receptors, angiotensin II promotes tissue inflammation through upregulation of adhesion molecules, increasing vascular permeability, and thus, enhancing neutrophil infiltration, which contributes to gut ulceration [9].…”

Section: Introductionmentioning

confidence: 99%

“…It also increases the release of proinflammatory cytokines such as TNF-α, probably, through activation of NF-κB. Additionally, Ang II triggers oxidative stress via activation of NADH/NADPH oxidase with consequent generation of superoxide anions [8].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2014

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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.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2014

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COVID‐19 and inflammatory bowel disease crosstalk: From emerging association to clinical proposal

Tao

Wang

Yang

et al. 2022

Journal of Medical Virology

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Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection can cause coronavirus disease 2019 (COVID‐19), an acute respiratory inflammation that has emerged worldwide since December 2019, and it quickly became a global epidemic. Inflammatory bowel disease (IBD) is a group of chronic nonspecific intestinal inflammatory diseases whose etiology has not been elucidated. The two have many overlapping symptoms in clinical presentation, such as abdominal pain, diarrhea, pneumonia, etc. Imbalance of the autoimmune system in IBD patients and long‐term use of immunosuppressive drugs may increase the risk of infection; and systemic symptoms caused by COVID‐19 may also induce or exacerbate intestinal inflammation. It has been found that the SARS‐CoV‐2 receptor angiotensin converting enzyme 2, which is highly expressed in the lung and intestine, is an inflammatory protective factor, and is downregulated and upregulated in COVID‐19 and IBD, respectively, suggesting that there may be a coregulatory pathway. In addition, the immune activation pattern of COVID‐19 and the cytokine storm in the inflammatory response have similar roles in IBD, indicating that the two diseases may influence each other. Therefore, this review aimed to address the following research questions: whether SARS‐CoV‐2 infection leads to the progression of IBD; whether IBD increases the risk of COVID‐19 infection and poor prognosis; possible common mechanisms and genetic cross‐linking between the two diseases; new treatment and care strategies for IBD patients, and the feasibility and risk of vaccination in the context of the COVID‐19 epidemic.

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PD123319, angiotensin II type II receptor antagonist, inhibits oxidative stress and inflammation in 2, 4-dinitrobenzene sulfonic acid-induced colitis in rat and ameliorates colonic contractility

Zizzo

Caldara

Bellanca³

et al. 2019

Inflammopharmacol

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Angiotensin II, the main effector of renin angiotensin system, plays an important role in the inflammatory process and most of its effects are mediated through the AT1 receptor activation. However, the knowledge about the AT2 receptor involvement in this process is still evolving. We previously found that in an experimental model of colitis, AT2 receptor activation can contribute to the impairment of the muscle contractility in vitro in the course of inflammation. Here, we investigated the potential alleviating effects of the in vivo treatment of PD123319 (1)(2)(3)(4) 4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid ditrifluoroacetate), AT2 receptor antagonist, in 2,4-dinitrobenzene sulfonic acid (DNBS)-induced rat model of colitis. The effects of i.p PD123319 (0.3, 3 and 10 mg/kg) administration to rats subjected to intra-rectal DNBS instillation were investigated. The study revealed that the colon injury and the inflammatory signs were ameliorated by PD123319 when visualized by the histopathological examination. The colon shortening, myeloperoxidase activity, and colonic expression of IL-1β, IL-6 and iNOS were downregulated in a dose-dependent manner in DNBS-induced colitis rats treated with PD123319 and the anti-oxidant defense machinery was also improved. The mechanism of these beneficial effects was found in the ability of PD123319 to inhibit NF-κB activation induced by DNBS. The colonic contractility in inflamed tissues was also improved by PD123319 treatment. In conclusion, our data have demonstrated previously that undescribed proinflammatory effects for the AT2 receptors in DNBS-induced colitis in rats in which they are mediated likely by NF-κB activation and reactive oxygen species generation. Moreover, when the inflammatory process is mitigated by the AT2 receptor antagonist treatment, the smooth muscle is able to recover its functionality. Keywords Inflammation • Angiotensin • AT2 receptor • Inflammatory bowel diseaseRecent data indicate that RAS is well expressed and active in the GI tract and it can also play a major role in several gut processes, including absorption, secretion, and motility (Ewert et al. 2006;Fishlock and Gunn 1970; Mastropaolo et al. 2013 Mastropaolo et al. , 2015.Moreover, data are accumulating suggesting an involvement of RAS in diseases such as GI cancer, mesenteric ischemia, motility disorders, and particularly inflammatory diseases (Shi et al. 2016). The RAS is a multi-component cascade with renin as the rate-limiting enzyme that cleaves angiotensinogen to angiotensin (Ang) I, which is further cleaved by angiotensin-converting enzyme (ACE) to Ang II. Ang II is the main effector of the RAS, it acts by binding to the angiotensin receptors (AT1 and AT2), which are found in many cell types including intestinal epithelial cells and mucosal immune cells (Fandriks 2011). AT1 receptors mediate all classical actions of Ang II in the target cells. AT2 receptors, indeed, in many instances counteract AT1 Inflammopharmacology * Maria Grazia Zizzo

show abstract

ACE inhibitors and angiotensin II receptor antagonists in Crohn’s disease management

Cited by 18 publications

References 60 publications

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

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

COVID‐19 and inflammatory bowel disease crosstalk: From emerging association to clinical proposal

PD123319, angiotensin II type II receptor antagonist, inhibits oxidative stress and inflammation in 2, 4-dinitrobenzene sulfonic acid-induced colitis in rat and ameliorates colonic contractility

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