Protective effects of mito-TEMPO against doxorubicin cardiotoxicity in mice
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. 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. 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). Our results indicate that mito-T protects mice against DOX-induced cardiotoxicity. ; Fundacao de Amparo a Pesquisa do Estado da Bahia-FAPESB, State Government of Bahia, Brazil ; Fundacao Oswaldo Cruz, Brazil ; Conselho Nacional de Desenvolvimento Cientifico e Tecnologico-CNPq, Ministry of Science and Technology, Brazil ; Fundacao Oswaldo Cruz, Goncallo Moniz Res Ctr, Rua Waldemar Falcao 121, BR-40296710 Salvador, BA, Brazil ; Univ Fed Sao Paulo, Lab Imunol Celular & Bioquim Fungos & Protozoario, Sao Paulo, Brazil ; UCL, London, England ; Univ Fed Sao Paulo, Lab Imunol Celular & Bioquim Fungos & Protozoario, Sao Paulo, Brazil ; Web of Science