Abstract
Mitochondria have long been involved in several cellular processes beyond its role in energy production. The importance of this organelle for cardiac tissue homeostasis has been greatly investigated and its impairment can lead to cell death and consequent organ failure. Several compounds have been described in the literature as having direct effects on cardiac mitochondria which can provide a mechanistic explanation for their toxicological or pharmacological effects. The present review describes one classic example of druginduced cardiac mitochondrial toxicity and another case of drug-induced mitochondrial protection. For the former, we present the case of doxorubicin, an anticancer agent whose treatment is associated with a cumulative and dose-dependent cardiomyopathy with a mitochondrial etiology. Following this, we present the case of carvedilol, a β-blocker with intrinsic antioxidant activity, which has been described to protect cardiac mitochondria from oxidative injury. The final part of the review integrates information from the previous chapters, demonstrating how carvedilol can contribute to reduce doxorubicin toxicity on cardiac mitochondria. The two referred examples result in important take-home messages: a) drug-induced cardiac mitochondrial dysfunction is an important contributor for drug-associated organ failure, b) protection of mitochondrial function is involved in the beneficial impact of some clinically-used drugs and c) a more accurate prediction of toxic vs. beneficial effects should be an important component of drug development by the pharmaceutical industry.
Keywords: Cardioprotection, carvedilol, doxorubicin, heart, mitochondria, toxicity, oxidative stress, apoptosis, metalloproteinases, anthracyclines
Current Pharmaceutical Design
Title: Drug-induced Cardiac Mitochondrial Toxicity and Protection: From Doxorubicin to Carvedilol
Volume: 17 Issue: 20
Author(s): Goncalo C. Pereira, Ana M. Silva, Catia V. Diogo, Filipa S. Carvalho, Pedro Monteiro and Paulo J. Oliveira
Affiliation:
Keywords: Cardioprotection, carvedilol, doxorubicin, heart, mitochondria, toxicity, oxidative stress, apoptosis, metalloproteinases, anthracyclines
Abstract: Mitochondria have long been involved in several cellular processes beyond its role in energy production. The importance of this organelle for cardiac tissue homeostasis has been greatly investigated and its impairment can lead to cell death and consequent organ failure. Several compounds have been described in the literature as having direct effects on cardiac mitochondria which can provide a mechanistic explanation for their toxicological or pharmacological effects. The present review describes one classic example of druginduced cardiac mitochondrial toxicity and another case of drug-induced mitochondrial protection. For the former, we present the case of doxorubicin, an anticancer agent whose treatment is associated with a cumulative and dose-dependent cardiomyopathy with a mitochondrial etiology. Following this, we present the case of carvedilol, a β-blocker with intrinsic antioxidant activity, which has been described to protect cardiac mitochondria from oxidative injury. The final part of the review integrates information from the previous chapters, demonstrating how carvedilol can contribute to reduce doxorubicin toxicity on cardiac mitochondria. The two referred examples result in important take-home messages: a) drug-induced cardiac mitochondrial dysfunction is an important contributor for drug-associated organ failure, b) protection of mitochondrial function is involved in the beneficial impact of some clinically-used drugs and c) a more accurate prediction of toxic vs. beneficial effects should be an important component of drug development by the pharmaceutical industry.
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Cite this article as:
C. Pereira Goncalo, M. Silva Ana, V. Diogo Catia, S. Carvalho Filipa, Monteiro Pedro and J. Oliveira Paulo, Drug-induced Cardiac Mitochondrial Toxicity and Protection: From Doxorubicin to Carvedilol, Current Pharmaceutical Design 2011; 17 (20) . https://dx.doi.org/10.2174/138161211796904812
DOI https://dx.doi.org/10.2174/138161211796904812 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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