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
  • 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: [email protected].
  • 6. Department of Orthopedics, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, 218 Jixi Road, Hefei 230022, China. Electronic address: [email protected].
  • 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: [email protected].
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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