线粒体靶向抗氧化剂Mito-TEMPO对小鼠阿霉素心脏毒性的保护作用
Protective effects of mito-TEMPO against doxorubicin cardiotoxicity in mice.
作者信息
Rocha Viviane Costa Junqueira, França Luciana Souza de Aragão, de Araújo Cintia Figueiredo, Ng Ayling Martins, de Andrade Candace Machado, Andrade André Cronemberger, Santos Emanuelle de Souza, Borges-Silva Mariana da Cruz, Macambira Simone Garcia, Noronha-Dutra Alberto Augusto, Pontes-de-Carvalho Lain Carlos
机构信息
Gonçallo Moniz Research Center, Fundação Oswaldo Cruz, Rua Waldemar Falcão 121, Salvador, BA, 40296-710, Brazil.
Laboratório de Imunologia Celular e Bioquímica de Fungos e Protozoários, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
出版信息
Cancer Chemother Pharmacol. 2016 Mar;77(3):659-62. doi: 10.1007/s00280-015-2949-7. Epub 2015 Dec 28.
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.
目的
阿霉素（DOX）是一种广泛用于治疗多种人类肿瘤的化疗药物。然而，心脏毒性的出现限制了其应用。本研究的目的是评估线粒体靶向抗氧化剂（mito-TEMPO，mito-T）作为一种保护剂对阿霉素诱导的小鼠心脏毒性的可能疗效。
方法
C57BL/6小鼠分别以低剂量（5mg/kg体重）或高剂量（20mg/kg体重）腹腔注射mito-T两次，并以阿霉素（24mg/kg体重）或生理盐水（0.1mL/20g体重）腹腔注射一次。在注射阿霉素48小时后，评估脂质过氧化标志物丙二醛（MLDA）的水平以及血清肌酸激酶水平。
结果
阿霉素诱导了心脏线粒体的脂质过氧化（p<0.001），低剂量mito-T处理的阿霉素处理小鼠的MLDA水平显著低于仅接受阿霉素处理的小鼠（p<0.01）。此外，单独给予mito-T与对照组相比未引起任何显著变化。另外，高剂量mito-T处理的阿霉素处理小鼠与单独接受阿霉素处理的小鼠相比，血清总CK水平降低（p<0.05）。
结论
我们的结果表明mito-T可保护小鼠免受阿霉素诱导的心脏毒性。
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