Attenuation of Doxorubicin-induced Cardiotoxicity by Tadalafil: A Long Acting Phosphodiesterase-5 Inhibitor.
نویسندگان
چکیده
Doxorubicin (DOX) is a broad spectrum antineoplastic drug widely used in the treatment of several hematogenous and solid human malignancies. Despite its excellent clinical efficacy as a chemotherapeutic agent, its therapeutic usage has been restricted due to its cardiotoxicity. Phosphodiesterase-5 (PDE-5) inhibitors or erectile dysfunction drugs including sildenafil, have been shown to have powerful cardioprotective effect against injuries under a variety of experimental situations including ischemia/reperfusion injury, myocardial infarction and DOX-induced cardiomyopathy. We studied the effect of - tadalafil, a long acting PDE-5 inhibitor in preventing damage in the heart with DOX treatment. Our results showed that tadalafil improved left ventricular function and survival by attenuating DOX-induced apoptosis and cardiac oxidative stress without interfering with the anti-tumor efficacy of DOX in both in vitro and in vivo tumor models. Herein, we present an overview of our study, and consider the potential mechanisms by which tadalafil, at therapeutically relevant concentrations mediate beneficial cardioprotective effects in DOX cardiotoxicity. Based on our current and previously published studies, we propose that the class of PDE-5 inhibitors can represent a novel approach which can be exploited for achieving therapeutic benefit in the treatment of DOX-induced cardiotoxicity in patients.
منابع مشابه
Long-acting phosphodiesterase-5 inhibitor tadalafil attenuates doxorubicin-induced cardiomyopathy without interfering with chemotherapeutic effect.
Doxorubicin (DOX) is one of the most effective anticancer drugs. However, its cardiotoxicity remains a clinical concern that severely restricts its therapeutic usage. We designed this study to investigate whether tadalafil, a long-acting phosphodiesterase-5 (PDE-5) inhibitor, protects against DOX-induced cardiotoxicity. We also sought to delineate the cellular and molecular mechanisms underlyin...
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عنوان ژورنال:
- Molecular and cellular pharmacology
دوره 2 5 شماره
صفحات -
تاریخ انتشار 2010