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Carvedilol-mediated antioxidant protection against doxorubicin-induced cardiac mitochondrial toxicity.
Toxicol Appl Pharmacol 2004; 200(2):159-68TA

Abstract

The cardiotoxicity associated with doxorubicin (DOX) therapy limits the total cumulative dose and therapeutic success of active anticancer chemotherapy. Cardiac mitochondria are implicated as primary targets for DOX toxicity, which is believed to be mediated by the generation of highly reactive free radical species of oxygen from complex I of the mitochondrial electron transport chain. The objective of this study was to determine if the protection demonstrated by carvedilol (CV), a beta-adrenergic receptor antagonist with strong antioxidant properties, against DOX-induced mitochondrial-mediated cardiomyopathy [Toxicol. Appl. Pharmacol. 185 (2002) 218] is attributable to its antioxidant properties or its beta-adrenergic receptor antagonism. Our results confirm that DOX induces oxidative stress, mitochondrial dysfunction, and histopathological lesions in the cardiac tissue, all of which are inhibited by carvedilol. In contrast, atenolol (AT), a beta-adrenergic receptor antagonist lacking antioxidant properties, preserved phosphate energy charge but failed to protect against any of the indexes of DOX-induced oxidative mitochondrial toxicity. We therefore conclude that the cardioprotective effects of carvedilol against DOX-induced mitochondrial cardiotoxicity are due to its inherent antioxidant activity and not to its beta-adrenergic receptor antagonism.

Authors+Show Affiliations

Centre of Neurosciences and Cellular Biology of Coimbra, Department of Zoology, University of Coimbra, Portugal.No affiliation info availableNo 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
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15476868

Citation

Oliveira, Paulo J., et al. "Carvedilol-mediated Antioxidant Protection Against Doxorubicin-induced Cardiac Mitochondrial Toxicity." Toxicology and Applied Pharmacology, vol. 200, no. 2, 2004, pp. 159-68.
Oliveira PJ, Bjork JA, Santos MS, et al. Carvedilol-mediated antioxidant protection against doxorubicin-induced cardiac mitochondrial toxicity. Toxicol Appl Pharmacol. 2004;200(2):159-68.
Oliveira, P. J., Bjork, J. A., Santos, M. S., Leino, R. L., Froberg, M. K., Moreno, A. J., & Wallace, K. B. (2004). Carvedilol-mediated antioxidant protection against doxorubicin-induced cardiac mitochondrial toxicity. Toxicology and Applied Pharmacology, 200(2), pp. 159-68.
Oliveira PJ, et al. Carvedilol-mediated Antioxidant Protection Against Doxorubicin-induced Cardiac Mitochondrial Toxicity. Toxicol Appl Pharmacol. 2004 Oct 15;200(2):159-68. PubMed PMID: 15476868.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Carvedilol-mediated antioxidant protection against doxorubicin-induced cardiac mitochondrial toxicity. AU - Oliveira,Paulo J, AU - Bjork,James A, AU - Santos,Maria S, AU - Leino,Richard L, AU - Froberg,M Kent, AU - Moreno,António J, AU - Wallace,Kendall B, PY - 2003/11/21/received PY - 2004/04/12/accepted PY - 2004/10/13/pubmed PY - 2004/12/16/medline PY - 2004/10/13/entrez SP - 159 EP - 68 JF - Toxicology and applied pharmacology JO - Toxicol. Appl. Pharmacol. VL - 200 IS - 2 N2 - The cardiotoxicity associated with doxorubicin (DOX) therapy limits the total cumulative dose and therapeutic success of active anticancer chemotherapy. Cardiac mitochondria are implicated as primary targets for DOX toxicity, which is believed to be mediated by the generation of highly reactive free radical species of oxygen from complex I of the mitochondrial electron transport chain. The objective of this study was to determine if the protection demonstrated by carvedilol (CV), a beta-adrenergic receptor antagonist with strong antioxidant properties, against DOX-induced mitochondrial-mediated cardiomyopathy [Toxicol. Appl. Pharmacol. 185 (2002) 218] is attributable to its antioxidant properties or its beta-adrenergic receptor antagonism. Our results confirm that DOX induces oxidative stress, mitochondrial dysfunction, and histopathological lesions in the cardiac tissue, all of which are inhibited by carvedilol. In contrast, atenolol (AT), a beta-adrenergic receptor antagonist lacking antioxidant properties, preserved phosphate energy charge but failed to protect against any of the indexes of DOX-induced oxidative mitochondrial toxicity. We therefore conclude that the cardioprotective effects of carvedilol against DOX-induced mitochondrial cardiotoxicity are due to its inherent antioxidant activity and not to its beta-adrenergic receptor antagonism. SN - 0041-008X UR - https://www.unboundmedicine.com/medline/citation/15476868/Carvedilol_mediated_antioxidant_protection_against_doxorubicin_induced_cardiac_mitochondrial_toxicity_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0041008X04002194 DB - PRIME DP - Unbound Medicine ER -