CAS Key Laboratory of Molecular Nanostructure and Nanotechnology, and Beijing National Laboratory for Molecular Sciences, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, 100190, Beijing, China.
University of Chinese Academy of Sciences, 100049, Beijing, China.
Sci Rep. 2018 Nov 8;8(1):16573. doi: 10.1038/s41598-018-34967-7.
Despite the great efforts for tumor therapy in the last decades, currently chemotherapy induced toxicity remains a formidable problem for cancer patients, and it usually prohibits the cancer therapy from successful completion due to severe side effects. In general, the main side effects of chemotherapeutic agents are from the as-produced reactive oxygen species (ROS) that not only harm the tumor cells but also damage the patients' organs. Here we report the application of amino acid derivatives of fullerene (AADF) in the chemotherapy which strongly scavenge the excess ROS to protect the tested mice against the chemotherapy-induced hepatotoxicity and cardiotoxicity. Two amino acids, i.e., L-lysine and β-alanine were separately employed to chemically modify C fullerene, and L-lysine derivative of fullerene (C-Lys) exhibits superior radical scavenging activity to β-alanine derivative of C (C-Ala). As expected, C-Lys show much better protective effect than C-Ala against the chemotherapy injuries in vivo, which is verified by various histopathological, haematological examinations and antioxidative enzyme studies. Moreover, the L-glutathione level is increased and the cytochrome P-450 2E1 expression is inhibited. They are potentially developed as promising bodyguards for chemotherapy protection.
尽管在过去几十年中，肿瘤治疗领域做出了巨大努力，但目前化疗诱导的毒性仍然是癌症患者面临的一个严重问题，由于严重的副作用，通常会阻止癌症治疗的成功完成。一般来说，化疗药物的主要副作用来自于产生的活性氧（ROS），它不仅会伤害肿瘤细胞，还会损害患者的器官。在这里，我们报告了富勒烯氨基酸衍生物（AADF）在化疗中的应用，它可以强烈清除多余的 ROS，从而保护实验小鼠免受化疗引起的肝毒性和心脏毒性。我们分别使用两种氨基酸，即赖氨酸和β-丙氨酸，对 C 富勒烯进行化学修饰，富勒烯赖氨酸衍生物（C-Lys）表现出比 C 富勒烯β-丙氨酸衍生物（C-Ala）更强的自由基清除活性。不出所料，C-Lys 在体内对化疗损伤的保护作用明显优于 C-Ala，这通过各种组织病理学、血液学检查和抗氧化酶研究得到了验证。此外，谷胱甘肽水平增加，细胞色素 P-450 2E1 表达受到抑制。它们有望成为化疗保护的有前途的“保镖”。
