Literature DB >> 20826257

Protective effects of the angiotensin II receptor blocker telmisartan on epirubicin-induced inflammation, oxidative stress, and early ventricular impairment.

Christian Cadeddu1, Alessandra Piras, Giovanni Mantovani, Martino Deidda, Mariele Dessì, Clelia Madeddu, Elena Massa, Giuseppe Mercuro.   

Abstract

BACKGROUND: Oxidative stress and RAAS play an important role in the occurrence of anthracyclines-induced cardiotoxicity. Telmisartan, an angiotensin II type 1 receptor blocker, inhibits activation of superoxide sources and induces anti-inflammatory effects.
METHODS: The possible role of telmisartan in preventing myocardial damage induced by epirubicin (EPI) was investigated. Forty-nine patients free from cardiovascular diseases affected by a variety of solid cancers were examined. Eligible patients were randomized to receive telmisartan (40 mg/d; TEL, n = 25) or placebo (PLA, n = 24) starting 1 week before chemotherapy. Patients were studied by means of echocardiography, tissue Doppler, and strain and strain rate (SR) imaging. We also measured plasma levels of inflammatory and oxidative stress markers. All parameters were assessed at baseline and 7 days after every new EPI dose of 100 mg/m(2).
RESULTS: An impairment of the SR peak was observed at the EPI dose of 200 mg/m(2), with no significant differences between TEL and PLA (1.41 +/- 0.31 vs 1.59 +/- 0.36/s). At growing cumulative doses of EPI, SR normalized only in TEL, showing a significant difference in comparison to PLA at EPI doses of 300 mg/m(2) (1.69 +/- 0.42 vs 1.34 +/- 0.18/s, P < .001) and 400 mg/m(2) (1.74 +/- 0.27 vs 1.38 +/- 0.24/s, P < .001). Moreover, a significant increase in reactive oxygen species and interleukin-6 was found in PLA; but these remained unchanged in TEL.
CONCLUSIONS: We confirmed that EPI-induced cardiotoxicity is primarily related to the inactivation of the cardiac antioxidant defenses. In addition, we showed that telmisartan can reduce EPI-induced radical species, antagonize the inflammation, and reverse the early myocardial impairment. 2010 Mosby, Inc. All rights reserved.

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Year:  2010        PMID: 20826257     DOI: 10.1016/j.ahj.2010.05.037

Source DB:  PubMed          Journal:  Am Heart J        ISSN: 0002-8703            Impact factor:   4.749


  41 in total

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