Effects of angiotensin II receptor blocker (candesartan) in daunorubicin-induced cardiomyopathic rats

Soga, Mayako; Kamal, Fadia; Watanabe, Kenichi; Ma, Minghong; Palaniyandi, Suresh S.; Prakash, Paras; Veeraveedu, Punniyakoti T.; Mito, Sayaka; Kunisaki, Megumi; Tachikawa, Hitoshi; Kodama, Makoto; Aizawa, Yoshifusa

doi:10.1016/j.ijcard.2005.08.061

Cited by 55 publications

(34 citation statements)

References 35 publications

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“…73 Treatment with the angiotensin receptor blocker candesartan also significantly improved the left ventricular function and reversed myocardial pathologic changes in the rat model of daunorubicininduced cardiomyopathy, suggesting its potential in limiting daunorubicin cardiotoxicity. 74 Among humans, similar results have been documented. In one observational study, 9 of 92 patients with advanced breast cancer were treated with high cumulative doses of epirubicin and subsequently developed severe systolic dysfunction with symptoms of HF.…”

Section: Angiotensin-converting Enzyme Inhibitors and Angiotensin Recsupporting

confidence: 68%

Pharmacologic Prevention of Anthracycline-Induced Cardiomyopathy

Maradia

Guglin

2009

Cardiology in Review

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Anthracyclines are highly effective anticancer drugs. However, a major factor limiting their use in humans is a cumulative, dose-related cardiotoxicity which can result in a permanent loss of cardiomyocytes, which ultimately leads to asymptomatic and symptomatic heart failure. Experiences with various approaches to reduce the cardiotoxicity of anthracyclines without jeopardizing their antineoplastic effects have been reported in the oncology literature. This article reviews the etiology and natural history of anthracycline-induced cardiotoxicity and provides options available for limiting and/or preventing cardiotoxicity.

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Section: Angiotensin-converting Enzyme Inhibitors and Angiotensin Recsupporting

confidence: 68%

Pharmacologic Prevention of Anthracycline-Induced Cardiomyopathy

Maradia

Guglin

2009

Cardiology in Review

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“…ACE inhibitors may also reduce interstitial fibrosis [72] and may be protective via modulation of PPARb/c gene expression [73]. Yet candesartan, an angiotensin II type 1 receptor antagonist, reversed fibrosis and apoptosis and improved myocyte diameter/body weight ratio in a model of daunorubicin-induced cardiomyopathy [74]. The ACE inhibitor valsartan added to the CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisolone) resulted protective improving echocardiographic and electrocardiographic parameters [75].…”

Section: Angiotensin-converting-enzyme Inhibitorsmentioning

confidence: 99%

Improving the preclinical models for the study of chemotherapy-induced cardiotoxicity: a Position Paper of the Italian Working Group on Drug Cardiotoxicity and Cardioprotection

et al. 2015

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Although treatment for heart failure induced by cancer therapy has improved in recent years, the prevalence of cardiomyopathy due to antineoplastic therapy remains significant worldwide. In addition to traditional mediators of myocardial damage, such as reactive oxygen species, new pathways and target cells should be considered responsible for the impairment of cardiac function during anticancer treatment. Accordingly, there is a need to develop novel therapeutic strategies to protect the heart from pharmacologic injury, and improve clinical outcomes in cancer patients. The development of novel protective therapies requires testing putative therapeutic strategies in appropriate animal models of chemotherapy-induced cardiomyopathy. This Position Paper of the Working Group on Drug Cardiotoxicity and Cardioprotection of the Italian Society of Cardiology aims to: (1) define the distinctive etiopatogenetic features of cardiac toxicity induced by cancer therapy in humans, which include new aspects of mitochondrial function and oxidative stress, neuregulin-1 modulation through the ErbB receptor family, angiogenesis inhibition, and cardiac stem cell depletion and/or dysfunction; (2) review the new, more promising therapeutic strategies for cardioprotection, aimed to increase the survival of patients with severe antineoplastic-induced cardiotoxicity; (3) recommend the distinctive pathological features of cardiotoxicity induced by cancer therapy in humans that should be present in animal models used to identify or to test new cardioprotective therapies.

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“…Angiotensin II plays a crucial role, not only as a vasoconstrictor agent, but also as a mitogenic factor by interacting with angiotensin II type-1 receptors (AT1Rs) in cardiovascular myocytes (9). Cardiac dysfunction after doxorubicin has not been demonstrated in the knockout rat for the AT1R gene, a finding confirmed by the absence of apoptosis and myofibrillar damage (10). In a recent study, the cardioprotective effect of the angiotensin receptor blocker (11), telmisartan (TEL), has been demonstrated in rats exposed to ANT (12).…”

Section: Introductionmentioning

confidence: 99%

Long-term protective effects of the angiotensin receptor blocker telmisartan on epirubicin-induced inflammation, oxidative stress and myocardial dysfunction

Dessì

Piras

Madeddu

et al. 2011

Experimental and Therapeutic Medicine

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Abstract. Chronic inflammation, oxidative stress and the renin-angiotensin system (RAS) play a significant role in chemotherapy-induced cardiotoxicity (CTX). Telmisartan (TEL), an antagonist of the angiotensin II type-1 receptor, was found to reduce anthracycline (ANT)-induced CTX. We carried out a phase II placebo (PLA)-controlled randomized trial to assess the possible role of TEL in the prevention of cardiac subclinical damage induced by epirubicin (EPI). Forty-nine patients (mean age ± SD, 53.0±8 years), cardiovascular diseasefree with cancer at different sites and eligible for EPI-based treatment, were randomized to one of two arms: TEL n=25; PLA n=24. A conventional echocardiography equipped with Tissue Doppler imaging, strain and strain rate (SR) was performed, and serum levels of proinflammatory cytokines, IL-6 and TNF-α, and oxidative stress parameters, reactive oxygen species (ROS) and glutathione peroxidase were determined. All assessments were carried out at baseline, after every 100 mg/m 2 of EPI dose and at the 12-month follow-up (FU). A significant reduction in the SR peak both in the TEL and PLA arms was observed at t 2 (cumulative dose of 200 mg/m 2 of EPI) in comparison to t 0 . Conversely, at t 3 (300 mg/m 2 EPI), t 4 (400 mg/m 2 EPI) and the 12-month FU, the SR increased reaching the normal range only in the TEL arm, while in the PLA arm the SR remained significantly lower as compared to t 0 (baseline). The differences between SR changes in the PLA and TEL arms were significant from 300 mg/m 2 EPI (t 3 ) up to the 12-month FU. Serum levels of IL-6 increased significantly in the PLA arm at 200 mg/m 2 EPI (t 2 ) in comparison to baseline, but remained unchanged in the TEL arm. The same trend was demonstrated for ROS levels which significantly increased at t 2 vs. baseline in the PLA arm, while remained unchanged in the TEL arm. The mean change in ROS and IL-6 at t 2 was significantly different between the two arms. In the present study, we confirmed at the 3-month FU a trend toward a decrease in ROS and IL-6 from t 2 in the PLA arm. Our results suggest that TEL is able to reverse acute (early) EPI-induced myocardial dysfunction and to maintain later a normal systolic function up to the 12-month FU. These effects are likely to be due to different mechanisms, RAS blockade and prevention of chronic inflammation/oxidative stress. IntroductionAnthracyclines (ANTs) are among the most effective anticancer drugs used in the treatment of a wide spectrum of malignancies. Regrettably, their clinical use is limited by the occurrence of dose-related cardiotoxicity (4).Several studies have shown that chemotherapy-induced cardiotoxicity (CTX) produced by ANTs is at least partially mediated by chronic inflammation and oxidative stress, with proinflammatory cytokines, interleukin-6 (IL-6) and tumor necrosis factor (TNF)-α and reactive oxygen species (ROS) (2) playing a central role (5,6). It has also been shown that the use of a conventional cardioprotective agent, such as dexrazoxane,

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Effects of angiotensin II receptor blocker (candesartan) in daunorubicin-induced cardiomyopathic rats

Cited by 55 publications

References 35 publications

Pharmacologic Prevention of Anthracycline-Induced Cardiomyopathy

Pharmacologic Prevention of Anthracycline-Induced Cardiomyopathy

Improving the preclinical models for the study of chemotherapy-induced cardiotoxicity: a Position Paper of the Italian Working Group on Drug Cardiotoxicity and Cardioprotection

Long-term protective effects of the angiotensin receptor blocker telmisartan on epirubicin-induced inflammation, oxidative stress and myocardial dysfunction

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