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Protective effects of mito-TEMPO against doxorubicin cardiotoxicity in mice

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Abstract

Purpose

Doxorubicin (DOX) is a chemotherapeutic that is widely used for the treatment of many human tumors. However, the development of cardiotoxicity has limited its use. The aim of the present study was to evaluate the possible efficacy of mito-TEMPO (mito-T) as a protective agent against DOX-induced cardiotoxicity in mice.

Methods

C57BL/6 mice were treated twice with mito-T at low (5 mg/kg body weight) or high (20 mg/kg body weight) dose and once with DOX (24 mg/kg body weight) or saline (0.1 mL/20 g body weight) by means of intraperitoneal injections. The levels of malondialdehyde (MLDA), a marker of lipid peroxidation, and serum levels of creatine kinase were evaluated 48 h after the injection of DOX.

Results

DOX induced lipid peroxidation in heart mitochondria (p < 0.001), and DOX-treated mice receiving mito-T at low dose had levels of MLDA significantly lower than the mice that received only DOX (p < 0.01). Furthermore, administration of mito-T alone did not cause any significant changes from control values. Additionally, DOX-treated mice treated with mito-T at high dose showed decrease in serum levels of total CK compared to mice treated with DOX alone (p < 0.05).

Conclusion

Our results indicate that mito-T protects mice against DOX-induced cardiotoxicity.

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Acknowledgments

This work was financially supported by Fundação de Amparo a Pesquisa do Estado da Bahia—FAPESB (www.fapesb.ba.gov.br), State Government of Bahia, Brazil. VCJR received a scholarship from Fundação Oswaldo Cruz, Brazil. LCPC have productivity scholarship from Conselho Nacional de Desenvolvimento Científico e Tecnológico—CNPq (www.cnpq.br), Ministry of Science and Technology, Brazil.

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Authors and Affiliations

  1. Gonçallo Moniz Research Center, Fundação Oswaldo Cruz, Rua Waldemar Falcão 121, Salvador, BA, 40296-710, Brazil

    Viviane Costa Junqueira Rocha, Luciana Souza de Aragão França, Cintia Figueiredo de Araújo, Ayling Martins Ng, Candace Machado de Andrade, Emanuelle de Souza Santos, Mariana da Cruz Borges-Silva, Simone Garcia Macambira, Alberto Augusto Noronha-Dutra & Lain Carlos Pontes-de-Carvalho

  2. Laboratório de Imunologia Celular e Bioquímica de Fungos e Protozoários, Universidade Federal de São Paulo, São Paulo, SP, Brazil

    André Cronemberger Andrade

  3. University College London, Gower Street, London, UK

    Alberto Augusto Noronha-Dutra

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  1. Viviane Costa Junqueira Rocha
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  2. Luciana Souza de Aragão França
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  3. Cintia Figueiredo de Araújo
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  8. Mariana da Cruz Borges-Silva
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Corresponding author

Correspondence to Lain Carlos Pontes-de-Carvalho.

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The authors have declared that no competing interests exist.

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Rocha, V.C.J., França, L.S.A., de Araújo, C.F. et al. Protective effects of mito-TEMPO against doxorubicin cardiotoxicity in mice. Cancer Chemother Pharmacol 77, 659–662 (2016). https://doi.org/10.1007/s00280-015-2949-7

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  • DOI: https://doi.org/10.1007/s00280-015-2949-7

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