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Protective Effect of a Mitochondria-Targeted Peptide against the Development of Chemotherapy-Induced Peripheral Neuropathy in Mice
ACS Chemical Neuroscience ( IF 4.1 ) Pub Date : 2018-04-16 00:00:00 , DOI: 10.1021/acschemneuro.8b00013 Satoshi Toyama 1, 2 , Naohito Shimoyama 3 , Hazel H. Szeto 4 , Peter W. Schiller 5, 6 , Megumi Shimoyama 3
ACS Chemical Neuroscience ( IF 4.1 ) Pub Date : 2018-04-16 00:00:00 , DOI: 10.1021/acschemneuro.8b00013 Satoshi Toyama 1, 2 , Naohito Shimoyama 3 , Hazel H. Szeto 4 , Peter W. Schiller 5, 6 , Megumi Shimoyama 3
Affiliation
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Several chemotherapeutic agents used for cancer treatment induce dose-limiting peripheral neuropathy that compromises patients’ quality of life and limits cancer treatment. Recently, mitochondrial dysfunction has been shown to be involved in the mechanism of chemotherapy-induced peripheral neuropathy. SS-20 is a mitochondria-targeted peptide that promotes mitochondrial respiration and restores mitochondrial bioenergetics. In the present study, we examined the protective effect of SS-20 against the development of chemotherapy-induced peripheral neuropathy utilizing a murine model of peripheral neuropathy induced by oxaliplatin, a first-line chemotherapy agent for colon cancer. Weekly administrations of oxaliplatin induced peripheral neuropathy as demonstrated by the development of neuropathic pain and loss of intraepidermal nerve fibers in the hind paw. Continuous administration of SS-20 protected against the development of oxaliplatin-induced neuropathic pain and mitigated the loss of intraepidermal nerve fibers to normal levels. Our findings suggest that SS-20 may be a drug candidate for the prevention of chemotherapy-induced peripheral neuropathy.
中文翻译：
线粒体靶向肽对小鼠化疗诱导的周围神经病发展的保护作用。
几种用于癌症治疗的化学治疗剂会引起剂量受限的周围神经病变，从而损害患者的生活质量并限制癌症的治疗。最近，线粒体功能障碍已被证明与化疗引起的周围神经病变的机制有关。SS-20是靶向线粒体的肽，可促进线粒体呼吸并恢复线粒体生物能。在本研究中，我们利用草酸奥沙利铂（一种结肠癌的一线化疗药物）诱导的周围神经病变的小鼠模型，研究了SS-20对化疗诱导的周围神经病变发展的保护作用。奥沙利铂每周给药可引起周围神经病变，这由后足神经性疼痛的发展和表皮内神经纤维的丧失所证实。连续施用SS-20可防止奥沙利铂引起的神经性疼痛的发生，并将表皮内神经纤维的损失减轻到正常水平。我们的研究结果表明SS-20可能是预防化疗引起的周围神经病的候选药物。
更新日期：2018-04-16
中文翻译：
线粒体靶向肽对小鼠化疗诱导的周围神经病发展的保护作用。
几种用于癌症治疗的化学治疗剂会引起剂量受限的周围神经病变，从而损害患者的生活质量并限制癌症的治疗。最近，线粒体功能障碍已被证明与化疗引起的周围神经病变的机制有关。SS-20是靶向线粒体的肽，可促进线粒体呼吸并恢复线粒体生物能。在本研究中，我们利用草酸奥沙利铂（一种结肠癌的一线化疗药物）诱导的周围神经病变的小鼠模型，研究了SS-20对化疗诱导的周围神经病变发展的保护作用。奥沙利铂每周给药可引起周围神经病变，这由后足神经性疼痛的发展和表皮内神经纤维的丧失所证实。连续施用SS-20可防止奥沙利铂引起的神经性疼痛的发生，并将表皮内神经纤维的损失减轻到正常水平。我们的研究结果表明SS-20可能是预防化疗引起的周围神经病的候选药物。
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