Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
Aging (Albany NY). 2021 Jan 2;13(3):3699-3711. doi: 10.18632/aging.202332.
Treatment of thoracic tumors with radiotherapy can lead to severe cardiac injury. We investigated the effects of dexrazoxane, a USFDA-approved cardioprotective drug administered with chemotherapy, on radiation-induced heart disease (RIHD) in a rat model. Male Sprague-Dawley rats were irradiated with a single dose of 20 Gy to the heart and treated with dexrazoxane at the time of irradiation and for 12 subsequent weeks. Dexrazoxane suppressed radiation-induced myocardial apoptosis and significantly reversed changes in serum cardiac troponin I levels and histopathological characteristics six months post-radiation. Treatment with dexrazoxane did not alter the radiosensitivity of thoracic tumors in a tumor formation experiment using male nude Balb/C mice with tumors generated by H292 cells. Dexrazoxane reduced the accumulation of reactive oxygen species in rat cardiac tissues, but not in tumors in nude mice. Transcriptome sequencing showed that and , which are involved in Toll-like receptor signaling, may be associated with the anti-RIHD effects of dexrazoxane. Immunohistochemistry revealed that dexrazoxane significantly decreased NF-κB p65 expression in cardiomyocytes. These findings suggest dexrazoxane may protect against RIHD by suppressing apoptosis and oxidative stress in cardiomyocytes.
放疗治疗胸部肿瘤可导致严重的心脏损伤。我们研究了美国食品和药物管理局批准的心脏保护药物右雷佐生（dexrazoxane）在大鼠模型中对放射性心脏病（RIHD）的影响，该药物与化疗联合使用。雄性 Sprague-Dawley 大鼠单次心脏照射 20 Gy，并在照射时及随后的 12 周内给予右雷佐生治疗。右雷佐生抑制了放射诱导的心肌细胞凋亡，并在放射后 6 个月显著逆转了血清心肌肌钙蛋白 I 水平和组织病理学特征的变化。在使用 H292 细胞生成肿瘤的雄性裸鼠肿瘤形成实验中，右雷佐生并未改变肿瘤的放射敏感性。右雷佐生减少了大鼠心脏组织中活性氧的积累，但对裸鼠肿瘤中没有影响。转录组测序显示，参与 Toll 样受体信号的和可能与右雷佐生的抗 RIHD 作用有关。免疫组织化学显示，右雷佐生显著降低了心肌细胞中 NF-κB p65 的表达。这些发现表明，右雷佐生可能通过抑制心肌细胞凋亡和氧化应激来预防 RIHD。
