Deferoxamine promotes recovery of traumatic spinal cord injury by inhibiting ferroptosis

• Published in: Neural regeneration research Vol. 14; no. 3; pp. 532 - 541
• Main Authors: Yao, Xue, Zhang, Yan, Hao, Jian, Duan, Hui-Quan, Zhao, Chen-Xi, Sun, Chao, Li, Bo, Fan, Bao-You, Wang, Xu, Li, Wen-Xiang, Fu, Xuan-Hao, Hu, Yong, Liu, Chang, Kong, Xiao-Hong, Feng, Shi-Qing
• Format: Journal Article
• Language: English
• Published: India Wolters Kluwer India Pvt. Ltd 01.03.2019; Medknow Publications and Media Pvt. Ltd; Medknow Publications & Media Pvt. Ltd; International Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin, China%Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, China; Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, China; Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neuro-repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, China; State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, China; International Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin, China; Department of Orthopedics, Nankai Hospital, Tianjin, China%Department of Orthopedic and Traumatology, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China%School of Medicine, Nankai University, Tianjin, China%Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, China; Medknow Publications & Media Pvt Ltd; Wolters Kluwer Medknow Publications
• Subjects: Animals; Apoptosis; Biochemistry; Care and treatment; Cell death; Contusions; Deferoxamine; FDA approval; Ferroptosis; Lipids; Medical research; nerve regeneration; iron; spinal cord injury; secondary injury; ferroptosis; deferoxamine; GPX4; xCT; treatment; astrogliosis; lipid peroxidation; neural regeneration; Novels; Physiological aspects; Spinal cord injuries; United States > US; China; spinal cord injury; treatment; deferoxamine; ferroptosis; neural regeneration; GPX4; secondary injury; xCT; iron; nerve regeneration; astrogliosis; lipid peroxidation
• ISSN: 1673-5374; 1876-7958
• DOI: 10.4103/1673-5374.245480

Ferroptosis is an iron-dependent novel cell death pathway. Deferoxamine, a ferroptosis inhibitor, has been reported to promote spinal cord injury repair. It has yet to be clarified whether ferroptosis inhibition represents the mechanism of action of Deferoxamine on spinal cord injury recovery. A rat model of Deferoxamine at thoracic 10 segment was established using a modified Allen's method. Ninety 8-week-old female Wistar rats were used. Rats in the Deferoxamine group were intraperitoneally injected with 100 mg/kg Deferoxamine 30 minutes before injury. Simultaneously, the Sham and Deferoxamine groups served as controls. Drug administration was conducted for 7 consecutive days. The results were as follows: (1) Electron microscopy revealed shrunken mitochondria in the spinal cord injury group. (2) The Basso, Beattie and Bresnahan locomotor rating score showed that recovery of the hindlimb was remarkably better in the Deferoxamine group than in the spinal cord injury group. (3) The iron concentration was lower in the Deferoxamine group than in the spinal cord injury group after injury. (4) Western blot assay revealed that, compared with the spinal cord injury group, GPX4, xCT, and glutathione expression was markedly increased in the Deferoxamine group. (5) Real-time polymerase chain reaction revealed that, compared with the Deferoxamine group, mRNA levels of ferroptosis-related genes Acyl-CoA synthetase family member 2 (ACSF2) and iron-responsive element-binding protein 2 (IREB2) were up-regulated in the Deferoxamine group. (6) Deferoxamine increased survival of neurons and inhibited gliosis. These findings confirm that Deferoxamine can repair spinal cord injury by inhibiting ferroptosis. Targeting ferroptosis is therefore a promising therapeutic approach for spinal cord injury.