%0 Journal Article
%T Alpha-tocopherol inhibits ferroptosis and promotes neural function recovery in rats with spinal cord injury via downregulating Alox15.
%A Zhu R
%A Kang Y
%A Li Q
%A Peng K
%A Shi X
%A Yin Z
%A Xuan Y
%J Biomed Pharmacother
%V 175
%N 0
%D 2024 Jun 14
%M 38754264
%F 7.419
%R 10.1016/j.biopha.2024.116734
%X 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.