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Drug-induced cardiac mitochondrial toxicity and protection: from doxorubicin to carvedilol.
Curr Pharm Des 2011; 17(20):2113-29CP

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 drug-induced cardiac mitochondrial toxicity and another case of drug-induced mitochondrial protection. For the former, we present the case for 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.

Authors+Show Affiliations

Center for Neuroscience and Cell Biology, Department of Life Sciences, University of Coimbra, Portugal.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

21718248

Citation

Pereira, Gonçalo C., et al. "Drug-induced Cardiac Mitochondrial Toxicity and Protection: From Doxorubicin to Carvedilol." Current Pharmaceutical Design, vol. 17, no. 20, 2011, pp. 2113-29.
Pereira GC, Silva AM, Diogo CV, et al. Drug-induced cardiac mitochondrial toxicity and protection: from doxorubicin to carvedilol. Curr Pharm Des. 2011;17(20):2113-29.
Pereira, G. C., Silva, A. M., Diogo, C. V., Carvalho, F. S., Monteiro, P., & Oliveira, P. J. (2011). Drug-induced cardiac mitochondrial toxicity and protection: from doxorubicin to carvedilol. Current Pharmaceutical Design, 17(20), pp. 2113-29.
Pereira GC, et al. Drug-induced Cardiac Mitochondrial Toxicity and Protection: From Doxorubicin to Carvedilol. Curr Pharm Des. 2011;17(20):2113-29. PubMed PMID: 21718248.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Drug-induced cardiac mitochondrial toxicity and protection: from doxorubicin to carvedilol. AU - Pereira,Gonçalo C, AU - Silva,Ana M, AU - Diogo,Cátia V, AU - Carvalho,Filipa S, AU - Monteiro,Pedro, AU - Oliveira,Paulo J, PY - 2011/06/08/received PY - 2011/06/27/accepted PY - 2011/7/2/entrez PY - 2011/7/2/pubmed PY - 2012/2/11/medline SP - 2113 EP - 29 JF - Current pharmaceutical design JO - Curr. Pharm. Des. VL - 17 IS - 20 N2 - 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 drug-induced cardiac mitochondrial toxicity and another case of drug-induced mitochondrial protection. For the former, we present the case for 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. SN - 1873-4286 UR - https://www.unboundmedicine.com/medline/citation/21718248/Drug_induced_cardiac_mitochondrial_toxicity_and_protection:_from_doxorubicin_to_carvedilol_ L2 - http://www.eurekaselect.com/74884/article DB - PRIME DP - Unbound Medicine ER -