title: Protective effects of mito-TEMPO against doxorubicin cardiotoxicity in mice.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  Our results indicate that mito-T protects mice against DOX-induced cardiotoxicity.
authors.affiliation: Gonçallo Moniz Research Center, Fundação Oswaldo Cruz, Rua Waldemar Falcão 121, Salvador, BA, 40296-710, Brazil.
authors.forename: Viviane Costa Junqueira
authors.initials: VC
authors.lastname: Rocha
authors.affiliation: Gonçallo Moniz Research Center, Fundação Oswaldo Cruz, Rua Waldemar Falcão 121, Salvador, BA, 40296-710, Brazil.
authors.forename: Luciana Souza de Aragão
authors.initials: LS
authors.lastname: França
authors.affiliation: Gonçallo Moniz Research Center, Fundação Oswaldo Cruz, Rua Waldemar Falcão 121, Salvador, BA, 40296-710, Brazil.
authors.forename: Cintia Figueiredo
authors.initials: CF
authors.lastname: de Araújo
authors.affiliation: Gonçallo Moniz Research Center, Fundação Oswaldo Cruz, Rua Waldemar Falcão 121, Salvador, BA, 40296-710, Brazil.
authors.forename: Ayling Martins
authors.initials: AM
authors.lastname: Ng
authors.affiliation: Gonçallo Moniz Research Center, Fundação Oswaldo Cruz, Rua Waldemar Falcão 121, Salvador, BA, 40296-710, Brazil.
authors.forename: Candace Machado
authors.initials: CM
authors.lastname: de Andrade
authors.affiliation: Laboratório de Imunologia Celular e Bioquímica de Fungos e Protozoários, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
authors.forename: André Cronemberger
authors.initials: AC
authors.lastname: Andrade
authors.affiliation: Gonçallo Moniz Research Center, Fundação Oswaldo Cruz, Rua Waldemar Falcão 121, Salvador, BA, 40296-710, Brazil.
authors.forename: Emanuelle de Souza
authors.initials: Ede S
authors.lastname: Santos
authors.affiliation: Gonçallo Moniz Research Center, Fundação Oswaldo Cruz, Rua Waldemar Falcão 121, Salvador, BA, 40296-710, Brazil.
authors.forename: Mariana da Cruz
authors.initials: Mda C
authors.lastname: Borges-Silva
authors.affiliation: Gonçallo Moniz Research Center, Fundação Oswaldo Cruz, Rua Waldemar Falcão 121, Salvador, BA, 40296-710, Brazil.
authors.forename: Simone Garcia
authors.initials: SG
authors.lastname: Macambira
authors.affiliation: Gonçallo Moniz Research Center, Fundação Oswaldo Cruz, Rua Waldemar Falcão 121, Salvador, BA, 40296-710, Brazil.|University College London, Gower Street, London, UK.
authors.forename: Alberto Augusto
authors.initials: AA
authors.lastname: Noronha-Dutra
authors.affiliation: Gonçallo Moniz Research Center, Fundação Oswaldo Cruz, Rua Waldemar Falcão 121, Salvador, BA, 40296-710, Brazil. lain.carvalho@gmail.com.
authors.forename: Lain Carlos
authors.initials: LC
authors.lastname: Pontes-de-Carvalho
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000633:toxicity*; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D066126:Cardiotoxicity / Q000209:etiology / Q000517:prevention & control*; D003402:Creatine Kinase / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D007274:Injections, Intraperitoneal; D015227:Lipid Peroxidation / Q000187:drug effects; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008929:Mitochondria, Heart / Q000187:drug effects / Q000473:pathology; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000903:Antibiotics, Antineoplastic; D002316:Cardiotonic Agents; C555916:MitoTEMPO; D009943:Organophosphorus Compounds; D010880:Piperidines; D008315:Malondialdehyde; D004317:Doxorubicin; D003402:Creatine Kinase
keywords: Cardiotoxicity; Doxorubicin; Mito-TEMPO; Mitochondria