Deferoxamine promotes recovery of traumatic spinal cord injury by inhibiting ferroptosis.
Yao X1, Zhang Y2, Hao J3, Duan HQ2, Zhao CX2, Sun C2, Li B2, Fan BY2, Wang X2, Li WX2, Fu XH2, Hu Y4, Liu C5, Kong XH5, Feng SQ6.
Neural Regen Res. 2019 Mar;14(3):532-541. doi: 10.4103/1673-5374.245480.
Abstract
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.
KEYWORDS:
GPX4; astrogliosis; deferoxamine; ferroptosis; iron; lipid peroxidation; nerve regeneration; neural regeneration; secondary injury; spinal cord injury; treatment; xCT
PMID: 30539824 DOI: 10.4103/1673-5374.245480
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