The Protective Effects of 5-Methoxytryptamine-α-lipoic Acid on Ionizing Radiation-Induced Hematopoietic Injury

• Published in: International journal of molecular sciences Vol. 17; no. 6; p. 935
• Main Authors: Li, Deguan, Tian, Zhenyuan, Tang, Weisheng, Zhang, Junling, Lu, Lu, Sun, Zhaojin, Zhou, Zewei, Fan, Feiyue
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 14-06-2016; MDPI AG
• Subjects: 5-Methoxytryptamine - chemical synthesis; 5-Methoxytryptamine - chemistry; 5-Methoxytryptamine - pharmacology; 5-Methoxytryptamine - therapeutic use; 5-methoxytryptamine-α-lipoic acid; Acute Radiation Syndrome - drug therapy; Acute Radiation Syndrome - metabolism; Acute Radiation Syndrome - prevention & control; Animals; DNA Damage - drug effects; Hematopoiesis - drug effects; hematopoietic cells; Histones - metabolism; ionizing radiation; Male; Melatonin - chemistry; Mice; Mice, Inbred C57BL; NADPH Oxidase 4; NADPH Oxidases - genetics; NADPH Oxidases - metabolism; radiation protection; Radiation, Ionizing; Radiation-Protective Agents - administration & dosage; Radiation-Protective Agents - chemical synthesis; Radiation-Protective Agents - pharmacology; Radiation-Protective Agents - therapeutic use; radioprotectors; reactive oxygen species (ROS); Reactive Oxygen Species - metabolism; Thioctic Acid - analysis; Thioctic Acid - chemical synthesis; Thioctic Acid - chemistry; Thioctic Acid - pharmacology; Thioctic Acid - therapeutic use; 5-methoxytryptamine-α-lipoic acid; radiation protection; hematopoietic cells; radioprotectors; reactive oxygen species (ROS); ionizing radiation
• ISSN: 1422-0067; 1422-0067
• DOI: 10.3390/ijms17060935

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.