Prevention of Fibrosis in Experimental Colitis by Captopril: the Role of tgf-β1

Wengrower, Dov; Zannineli, Giuliana; Pappo, Orit; Latella, Giovanni; Sestieri, M.; Villanova, Amancay; Faitelson, Yoram; Pines, Mark; Goldin, Eran

doi:10.1097/00054725-200409000-00007

Cited by 89 publications

(104 citation statements)

References 69 publications

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“…It is important to note that our findings are supported by other investigators who have recently identified a potential benefit in blocking the renninangiotensin (RAS) pathway in inflammatory bowel disease. Wengrower, et al showed that fibrotic changes were significantly diminished in a trinitrobenzene sulphonic acid (TNBS) induced model of colitis in rats (56). Blockade of the RAS pathway using angiotensinogenknock out mice also resulted in a diminution of the level of inflammation in this TNBS model (57).…”

Section: Discussionmentioning

confidence: 96%

Reduced Severity of a Mouse Colitis Model with Angiotensin Converting Enzyme Inhibition

et al. 2007

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Ulcerative colitis is characterized by elevated rates of epithelial cell apoptosis, and an up-regulation of pro-apoptotic cytokines including tumor necrosis factor alpha (TNF-α). Recently, angiotensin converting enzyme (ACE) has been shown to promote apoptosis. In addition, pharmacologic ACE inhibition (ACE-I) both prevents apoptosis and reduces TNF-α expression in vitro. We hypothesized that ACE-I, using enalaprilat, would decrease colonic epithelial cell apoptosis and reduce colitis severity in the dextran sulfate sodium (DSS)-induced colitis model in mice. We assessed the severity of colitis, and colonic epithelial cell apoptosis, after administration of DSS. Mice were given either daily ACE-I treatment or daily placebo. ACE-I treatment markedly improved clinical outcomes. In addition, ACE-I treatment significantly reduced the maximum histopathologic colitis grade. ACE-I also dramatically reduced the epithelial apoptotic rate. To investigate the mechanism by which ACE-I reduced apoptosis; we measured TNF-α, Bcl-2, and Bax expression. TNF-α mRNA was significantly lower with ACE-I treatment compared to placebo at every time point; as was the ratio of Bax to Bcl-2. We conclude that ACE-I reduces the severity of DSS-induced colitis and reduces epithelial cell apoptosis.

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Section: Discussionmentioning

confidence: 96%

Reduced Severity of a Mouse Colitis Model with Angiotensin Converting Enzyme Inhibition

et al. 2007

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“…ACE inhibitors have had mixed results in animal models of colitis. Wengrower et al, demonstrated that prophylactic administration of Captopril in TNBS colitis could reduce damages scores and fibrosis after 21 days, as well as the levels of Ang II and TGF-beta [13]. On the other hand treatment with the same inhibitor administered after the induction of acute colitis did not show significant benefits in the observed lesions at the dose tested [45].…”

Section: Discussionmentioning

confidence: 99%

“…This led us to hypothesize that the inhibition of Ang II could attenuate the inflammation and subsequent damage found in acute colitis. Recently it was demonstrated that an ACE inhibitor, Captopril, could reduce the levels of Ang II and the colonic fibrosis found in an animal model of colitis [13]. Moreover, losartan, an Ang II type I receptor blocker was found to have beneficial effects in colitic mice confirming the involvement of this receptor [14].…”

Section: Introductionmentioning

confidence: 94%

An angiotensin II receptor antagonist reduces inflammatory parameters in two models of colitis

Santiago

Rivera

Ferder

et al. 2008

Regulatory Peptides

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Little is known about the effects of the proinflammatory hormone Angiotensin II (Ang II) in inflammatory bowel disease. The aim of this study was to evaluate the effect of Valsartan (Diovan), an Ang II receptor antagonist, in two models of colitis.METHODS-Colitis was induced in Sprague-Dawley rats by administration of trinitrobenzene sulfonic acid (TNBS; 30mg in 50% ETOH ic) or 5% Dextran Sulphate Sodium (DSS) in drinking water ad libitum for 5 days. Valsartan was administered orally in drinking water (160mg/L) during thirty days prior to the induction of the colitis, and for 5 days after. All animals were evaluated for weight change, diarrhea, myeloperoxidase activity, macroscopic and microscopic damage. Cytokine levels in the colon were measured by ELISA, real time RT-PCR and immunohistochemistry.RESULTS-In the TNBS model, Valsartan reduced the macroscopic damage score, significantly decreased the microscopic damage (p<0.01), and accelerated weight gain after colitis. In the DSS colitis model, Valsartan treated animals had less diarrhea and microscopic damage. Valsartan reduced the protein levels of TGFβ (p<0.05), and IL-18 in the TNBS model, and led to over-expression of IL-10 mRNA in the DSS model.CONCLUSION-These data demonstrate a possible anti-inflammatory effect for Valsartan in colitis.

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“…These drugs have been shown to produce a number of beneficial antiinflammatory effects in rodent models of intestinal inflammation. [48][49][50][51][52][53] Though originally thought to exert their action predominantly via blockade of the effects of Ang II, recent evidence suggests some of the beneficial effects may be through upregulation of the alternative RAS with increased tissue Ang (1-7). [54][55][56] Hence, if translated to human trials in IBD, these inexpensive, readily available medications may be suitable for treatment of inflammation and fibrosis in IBD.…”

Section: (0-11)mentioning

confidence: 99%

Upregulation of circulating components of the alternative renin-angiotensin system in inflammatory bowel disease: A pilot study

Garg

Burrell

Velkoska

et al. 2014

J Renin Angiotensin Aldosterone Syst

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Introduction:The relationship between intestinal inflammation and circulating components of the renin-angiotensin system (RAS) is poorly understood. Materials and methods: Demographic and clinical data were obtained from healthy controls and patients with inflammatory bowel disease (IBD). Plasma concentrations of the classical RAS components (angiotensin-converting enzyme (ACE) and angiotensin II (Ang II)) and alternative RAS components (ACE2 and angiotensin (1-7) (Ang (1-7))) were analysed by radioimmuno-and enzymatic assays. Systemic inflammation was assessed using serum C-reactive protein (CRP), white cell count, platelet count and albumin, and intestinal inflammation by faecal calprotectin. Results: Nineteen healthy controls (11 female; mean age 38 years, range 23-68), 19 patients with Crohn's disease (11 female; aged 45 years, range 23-76) and 15 patients with ulcerative colitis (6 female; aged 42 years, 26-64) were studied. Circulating classical RAS component levels were similar across the three groups, whereas ACE2 activity and Ang (1-7) concentrations were higher in patients with IBD compared to controls (ACE2: 21.5 vs 13.3 pmol/ml/min, p<0.05; Ang (1-7): 22.8 vs 14.1 pg/ml, p<0.001). Ang (1-7) correlated weakly with platelet and white cell counts, but not calprotectin or CRP, in patients with IBD. Conclusions: Circulating components of the alternative RAS are increased in patients with IBD.

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Prevention of Fibrosis in Experimental Colitis by Captopril: the Role of tgf-β1

Cited by 89 publications

References 69 publications

Reduced Severity of a Mouse Colitis Model with Angiotensin Converting Enzyme Inhibition

Reduced Severity of a Mouse Colitis Model with Angiotensin Converting Enzyme Inhibition

An angiotensin II receptor antagonist reduces inflammatory parameters in two models of colitis

Upregulation of circulating components of the alternative renin-angiotensin system in inflammatory bowel disease: A pilot study

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