2. Academic Validation
  3. Alpha-tocopherol inhibits ferroptosis and promotes neural function recovery in rats with spinal cord injury via downregulating Alox15

Alpha-tocopherol inhibits ferroptosis and promotes neural function recovery in rats with spinal cord injury via downregulating Alox15

  • Biomed Pharmacother. 2024 Jun:175:116734. doi: 10.1016/j.biopha.2024.116734.
Rui Zhu 1,  Yu Kang 2,  Qiangwei Li 3,  Kai Peng 4,  Xuanming Shi 5,  Zongsheng Yin 6,  Yong Xuan 7
Affiliations

Affiliations

  • 1 Department of Orthopedics, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, 218 Jixi Road, Hefei 230022, China; Department of Orthopedics, Hefei Orthopedics Hospital, 58 Chaohu Northern Road, Hefei 238001, China.
  • 2 Department of Orthopedics, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, 218 Jixi Road, Hefei 230022, China.
  • 3 School of Basic Medical Sciences, Anhui Medical University, 81 Meishan Road, Hefei 230032, China.
  • 4 Department of Orthopedics, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, 218 Jixi Road, Hefei 230022, China; The Key Laboratory of Microbiology and Parasitology of Anhui Province, Anhui Medical University, 81 Meishan Road, Hefei 230032, China.
  • 5 School of Basic Medical Sciences, Anhui Medical University, 81 Meishan Road, Hefei 230032, China. Electronic address: xuanming.shi@ahmu.edu.cn.
  • 6 Department of Orthopedics, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, 218 Jixi Road, Hefei 230022, China. Electronic address: ahmu_zsyin@163.com.
  • 7 Department of Orthopedics, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, 218 Jixi Road, Hefei 230022, China; Department of Orthopedics, The Second People's Hospital of Hefei, 246 Heping Road, Hefei 230011, China. Electronic address: xy15251620255@163.com.
PMID: 38754264 DOI: 10.1016/j.biopha.2024.116734
Abstract

Spinal cord injury (SCI) is a type of central nervous system (CNS) injury in which Ferroptosis is becoming a promising target for treatment. Alpha-tocopherol (Vitamin E, Vit E) is a compound with anti-ferroptosis activity. The mechanism of alpha-tocopherol in regulating Ferroptosis after SCI has not been deeply studied. In this study, rats with SCI were treated by Alpha-tocopherol based on bioinformatic analysis and molecular docking prediction. Behavioral tests and histological findings showed that Alpha-tocopherol promoted neural function recovery and tissue repairment in rats with SCI. Subsequently, regulatory effects of Alpha-tocopherol on Alox15 and Ferroptosis were detected and then localized by immunofluorescence. In vitro, alpha-tocopherol improved the ROS accumulation, iron overload, lipid peroxidation and mitochondrial dysfunction. The effects of Alpha-tocopherol on the expression of Alox15, Ptgs2 and 4Hne were validated in vitro. Finally, the inhibitory effects of Alpha-tocopherol on Alox15 and Ferroptosis were weakened by the mutation of 87th residue of Alox15. In summary, alpha-tocopherol could alleviate SCI-induced Ferroptosis by downregulating Alox15 to promote neural function recovery in rats with SCI. Findings in this study could help further our understanding on SCI-induced Ferroptosis and provide a novel insight for treating SCI.

Keywords

Ferroptosis; Spinal cord injury; Vitamin E.

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