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Cited by 298Spinal Cord Injury ResearchFerroptosis and cancer prognosisNerve injury and regeneration

Deferoxamine promotes recovery of traumatic spinal cord injury by inhibiting ferroptosis

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Feng, Shi-Qing, Yao, Xue, Zhang, Yan, Hao, Jian, Duan, Hui-Quan, Zhao, Chen-Xi, Sun, Chao, Li, Bo +7 more·2019·Neural Regeneration Research
DOI 10.4103/1673-5374.245480PMC PMC6334606
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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.

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Authors
Feng, S.-Q., Yao, X., Zhang, Y., Hao, J., Duan, H.-Q., Zhao, C.-X., Sun, C., Li, B., Fan, B.-Y., Wang, X., Li, W.-X., Fu, X.-H., Hu, Y., Liu, C., & Kong, X.-H.
Affiliations
  • Nankai University (CN)
  • Tianjin Medical University General Hospital (CN)
  • University of Hong Kong (HK)
ORCID
Venue
Neural Regeneration Research
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2019
Volume
14
Issue
3
Pages
532
ISSN
1673-5374 (ISSN-L)
DOI
10.4103/1673-5374.245480
PMC
PMC6334606
OpenAlex
W2904457678
Cited by
298
References
2
Citations by year
2026: 31 · 2025: 50 · 2024: 61 · 2023: 48 · 2022: 57 · 2021: 27 · 2020: 17 · 2019: 7
FWCI
9.45
Type
journal article
Language
en
Update notices
correction (2019-06-01)
Open access
Licence
cc-by-nc-sa
Locations
  • Neural Regeneration Research (publishedVersion, cc-by-nc-sa)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Spinal Cord Injury Research
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Ferroptosis and cancer prognosis
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
Keywords
deferoxamine, traumatic spinal cord injury, ferroptosis, ferroptosis inhibition, neuroprotection, locomotor recovery, iron metabolism, GPX4, SLC7A11, glutathione, IREB2, gliosis, mitochondrial damage

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