Abstract
Nebivolol is a cardioselective beta-blocker (BB) currently used for the treatment
of hypertension. It has mild vasodilating properties attributed to its interaction
with the L-arginine/nitric oxide pathway, a property not shared by other BBs. Carvedilol
is a nonselective ß-adrenergic receptor antagonist that also blocks α1-adrenergic receptors and is a potent antioxidant. Anthracyclines (ANTs), daunorubicin
and doxorubicin, are commonly used in the treatment of several tumours, but their
cardiac toxicity prevents their use at maximum myelotoxic doses, representing an important
problem. In this study, we have evaluated the role of these BBs administered in combination
with ANTs (daunorubicin and doxorubicin) on a reduction in cardiac toxicity. The combination
of BB and ANTs has reduced the release of GSSG and GSH; in particular, co-treatment
with nebivolol to ANTs has shown a significant reduction. The total integrated creatine
kinase and troponin T activities were improved by BB and ANTs co-treatment. A significant
reduction of their release was observed when hearts were treated with nebivolol. Cardiac
tissue activity of gluthatione reductase was not significant and similar among experimental
groups. In contrast, gluthatione peroxidise, Mn-superoxide dismutase and nitrite/nitrate
release were increased after co-treatment with nebivolol. Finally, three parameters
have been used to evaluate the cardiac toxicity of ANTs: the left ventricular pressure
developed under a constant perfusion pressure (LVDP), the rate of variation of this
parameter during systole (contractility) (LV/dt)max and during diastole (relaxation) (LV(dP/dt)min. Combination with BB has shown a reduction in cardiac toxicity; in particular, nebivolol
has exerted the most significant cardioprotective effect.
Keywords
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Article info
Publication history
Published online: January 15, 2008
Accepted:
December 14,
2007
Received in revised form:
December 10,
2007
Received:
September 18,
2007
Identification
Copyright
© 2007 Elsevier Ltd. Published by Elsevier Inc. All rights reserved.
