Pathways of cardiac toxicity: comparison between chemotherapeutic drugs doxorubicin and mitoxantrone.
Arch Toxicol
; 90(9): 2063-2076, 2016 Sep.
Article
em En
| MEDLINE
| ID: mdl-27342245
ABSTRACT
Anthracyclines, e.g., doxorubicin (DOX), and anthracenediones, e.g., mitoxantrone (MTX), are drugs used in the chemotherapy of several cancer types, including solid and non-solid malignancies such as breast cancer, leukemia, lymphomas, and sarcomas. Although they are effective in tumor therapy, treatment with these two drugs may lead to side effects such as arrhythmia and heart failure. At the same clinically equivalent dose, MTX causes slightly reduced cardiotoxicity compared with DOX. These drugs interact with iron to generate reactive oxygen species (ROS), target topoisomerase 2 (Top2), and impair mitochondria. These are some of the mechanisms through which these drugs induce late cardiomyopathy. In this review, we compare the cardiotoxicities of these two chemotherapeutic drugs, DOX and MTX. As described here, even though they share similarities in their modes of toxicant action, DOX and MTX seem to differ in a key aspect. DOX is a more redox-interfering drug, while MTX induces energy imbalance. In addition, DOX toxicity can be explained by underlying mechanisms that include targeting of Top2 beta, mitochondrial impairment, and increases in ROS generation. These modes of action have not yet been demonstrated for MTX, and this knowledge gap needs to be filled.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
1_ASSA2030
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Doxorrubicina
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Mitoxantrona
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Miócitos Cardíacos
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Cardiopatias
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Antibióticos Antineoplásicos
Limite:
Animals
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Humans
Idioma:
En
Revista:
Arch Toxicol
Ano de publicação:
2016
Tipo de documento:
Article