Antineoplastic anthracycline therapy is limited by the cardiotoxicity of this class of compounds, and there is a continuing need to investigate and develop effective therapeutic agents to reduce cardiac damage induced by the anthracyclines. Inhibition of phosphodiesterase 5 has been shown to have protective effects in cardiac ischemia/reperfusion injury in rats; therefore, Koka et al. investigated the cardioprotective effects of the selective phosphodiesterase 5 inhibitor tadalafil on doxorubicin-induced cardiac damage and sought to delineate the cellular and molecular mechanisms underlying its cardioprotective effects. In an acute model of doxorubicin-induced cardiac damage, tadalafil significantly improved cardiac contractile function, attenuated doxorubicin-induced apoptosis and depletion of prosurvival proteins (including Bcl-2 and GATA-4 in the myocardium), attenuated cardiac oxidative stress through the up-regulation of mitochondrial superoxide dismutase, and increased cGMP levels and PGK activity in the myocardium; all of this was observed without a significant effect on the efficacy of doxorubicin. These results suggest that prophylactic treatment with tadalafil might be a promising therapy for doxorubicin-induced cardiotoxicity.
See article at J Pharmacol Exp Ther 2010, 334:1023–1030.
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