The Protective Effects of 5-Methoxytryptamine-α-lipoic Acid on Ionizing Radiation-Induced Hematopoietic Injury.
Antioxidants are prospective radioprotectors because of their ability to scavenge radiation-induced reactive oxygen species (ROS). The hematopoietic system is widely studied in radiation research because of its high radiosensitivity. In the present study, we describe the beneficial effects of 5-methoxytryptamine-α-lipoic acid (MLA), which was synthesized from melatonin and α-lipoic acid, against radiation-induced hematopoietic injury. MLA administration significantly enhanced the survival rate of mice after 7.2 Gy total body irradiation. The results showed that MLA not only markedly increased the numbers and clonogenic potential of hematopoietic cells but also decreased DNA damage, as determined by flow cytometric analysis of histone H2AX phosphorylation. In addition, MLA decreased the levels of ROS in hematopoietic cells by inhibiting NOX4 expression. These data demonstrate that MLA prevents radiation-induced hematopoietic syndrome by increasing the number and function of and by inhibiting DNA damage and ROS production in hematopoietic cells. These data suggest MLA is beneficial for the protection of radiation injuries.
Institute of Radiation Medicine, Chinese Academy of Medical Science and Peking Union Medical Collage, Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Tianjin 300192, China. lideguan@irm-cams.ac.cn.
Deguan
D
Li
Institute of Radiation Medicine, Chinese Academy of Medical Science and Peking Union Medical Collage, Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Tianjin 300192, China. tianzhenyuan1027@126.com.
Zhenyuan
Z
Tian
Institute of Radiation Medicine, Chinese Academy of Medical Science and Peking Union Medical Collage, Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Tianjin 300192, China. twsemail@126.com.
Weisheng
W
Tang
Institute of Radiation Medicine, Chinese Academy of Medical Science and Peking Union Medical Collage, Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Tianjin 300192, China. zhangjunling@irm-cams.ac.cn.
Junling
J
Zhang
Institute of Radiation Medicine, Chinese Academy of Medical Science and Peking Union Medical Collage, Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Tianjin 300192, China. lulu@irm-cams.ac.cn.
Lu
L
Lu
Institute of Radiation Medicine, Chinese Academy of Medical Science and Peking Union Medical Collage, Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Tianjin 300192, China. s654134369@126.com.
Zhaojin
Z
Sun
Institute of Radiation Medicine, Chinese Academy of Medical Science and Peking Union Medical Collage, Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Tianjin 300192, China. zhouzewei@irm-cams.ac.cn.
Zewei
Z
Zhou
Institute of Radiation Medicine, Chinese Academy of Medical Science and Peking Union Medical Collage, Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Tianjin 300192, China. fanfeiyue@irm-camc.ac.cn.
Feiyue
F
Fan
D008735:5-Methoxytryptamine / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D054508:Acute Radiation Syndrome / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control; D000818:Animals; D004249:DNA Damage / Q000187:drug effects; D006410:Hematopoiesis / Q000187:drug effects*; D006657:Histones / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D011839:Radiation, Ionizing; D011837:Radiation-Protective Agents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000378:metabolism; D008063:Thioctic Acid / Q000032:analysis* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*
D006657:Histones; D011837:Radiation-Protective Agents; D017382:Reactive Oxygen Species; D008735:5-Methoxytryptamine; D008063:Thioctic Acid; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C422943:Nox4 protein, mouse; D008550:Melatonin
5-methoxytryptamine-α-lipoic acid; hematopoietic cells; ionizing radiation; radiation protection; radioprotectors; reactive oxygen species (ROS)