Deferoxamine promotes recovery of traumatic spinal cord injury by inhibiting ferroptosis

Yao, Xuemei; Zhang, Yan; Hao, Junhua; Duan, Huiquan; Zhao, Chenxi; Sun, Chao; Лі, Бо; Fan, Baoyou; Wang, Xu; Li, Wenxiang; Fu, Xuanhao; Hu, Yong; Liu, Chang; Kong, Xiaohong; Feng, Shiqing

doi:10.4103/1673-5374.245480

Cited by 212 publications

(21 citation statements)

References 40 publications

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“…Therefore, anti-ferroptotic seems to have potential in SCI, though there are few studies. Feng et al (2019) established a rat model of DFO and confirmed the positive role of DFO in treating SCI. In the DFO group, there were lower iron concentrations, markedly increased GPX4 expression, and increased neuronal survival ( Feng et al, 2019 ).…”

Section: The Role and Mechanism Of Ferroptosis In Acute Cns Injuriesmentioning

confidence: 76%

“… Feng et al (2019) established a rat model of DFO and confirmed the positive role of DFO in treating SCI. In the DFO group, there were lower iron concentrations, markedly increased GPX4 expression, and increased neuronal survival ( Feng et al, 2019 ). In the study conducted by Zhang Y. et al (2019) treatment with the third-generation ferrostatin, SRS 16-86, increased neuronal survival and promoted locomotor recovery in the SCI model, providing potential therapeutic strategies for SCI.…”

Section: The Role and Mechanism Of Ferroptosis In Acute Cns Injuriesmentioning

confidence: 76%

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Ferroptosis in Acute Central Nervous System Injuries: The Future Direction?

Shen

Lin

et al. 2020

Front. Cell Dev. Biol.

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Acute central nervous system (CNS) injuries, such as stroke, traumatic brain injury (TBI), and spinal cord injury (SCI) present a grave health care challenge worldwide due to high morbidity and mortality, as well as limited clinical therapeutic strategies. Established literature has shown that oxidative stress (OS), inflammation, excitotoxicity, and apoptosis play important roles in the pathophysiological processes of acute CNS injuries. Recently, there have been many studies on the topic of ferroptosis, a form of regulated cell death characterized by the accumulation of iron-dependent lipid peroxidation. Some studies have revealed an emerging connection between acute CNS injuries and ferroptosis. Ferroptosis, induced by the abnormal metabolism of lipids, glutathione (GSH), and iron, can accelerate acute CNS injuries. However, pharmaceutical agents, such as iron chelators, ferrostatin-1 (Fer-1), and liproxstatin-1 (Lip-1), can inhibit ferroptosis and may have neuroprotective effects after acute CNS injuries. However, the specific mechanisms underlying this connection has not yet been clearly elucidated. In this paper, we discuss the general mechanisms of ferroptosis and its role in stroke, TBI, and SCI. We also summarize ferroptosis-related drugs and highlight the potential therapeutic strategies in treating various acute CNS injuries. Additionally, this paper suggests a testable hypothesis that ferroptosis may be a novel direction for further research of acute CNS injuries by providing corresponding evidence.

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Section: The Role and Mechanism Of Ferroptosis In Acute Cns Injuriesmentioning

confidence: 76%

Section: The Role and Mechanism Of Ferroptosis In Acute Cns Injuriesmentioning

confidence: 76%

Ferroptosis in Acute Central Nervous System Injuries: The Future Direction?

Shen

Lin

et al. 2020

Front. Cell Dev. Biol.

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“…Does ferroptosis exist in SCI? Some scholars have found that the ferroptosis markers in the spinal cord tissue of SCI rats were obviously changed, and using transmission electron microscopy, they also observed changes in the mitochondria characteristic of ferroptosis, thus confirming that ferroptosis plays an important role in SCI [ 35 ]. After SCI occurred, the spinal cord bled profusely, red blood cells accumulated, cells broke up, and hemolysis occurred, and there was a local iron overload.…”

Section: Progress In Research On Ferroptosis In Scimentioning

confidence: 95%

“…Subsequent studies confirmed that ferroptosis was an important cause of the serious consequences of secondary injury after SCI, and DFO could promote the recovery of motor function in SCI rats by inhibiting ferroptosis [ 35 ]. Galluzzi et al [ 89 ] added ferrous ions to the culture dish of spinal nerve cells and observed that the amount of lipid peroxidation metabolites was proportional to the level of iron and positively correlated with neuronal inactivation.…”

Section: Progress In Research On Ferroptosis In Scimentioning

confidence: 99%

The Latest View on the Mechanism of Ferroptosis and Its Research Progress in Spinal Cord Injury

Chen

Liu

et al. 2020

Oxidative Medicine and Cellular Longevity

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Ferroptosis is a recently identified nonapoptotic form of cell death whose major markers are iron dependence and accumulation of lipid reactive oxygen species, accompanied by morphological changes such as shrunken mitochondria and increased membrane density. It appears to contribute to the death of tumors, ischemia-reperfusion, acute renal failure, and nervous system diseases, among others. The generative mechanism of ferroptosis includes iron overloading, lipid peroxidation, and downstream execution, while the regulatory mechanism involves the glutathione/glutathione peroxidase 4 pathway, as well as the mevalonate pathway and the transsulfuration pathway. In-depth research has continuously developed and enriched knowledge on the mechanism by which ferroptosis occurs. In recent years, reports of the noninterchangeable role played by selenium in glutathione peroxidase 4 and its function in suppressing ferroptosis and the discovery of ferroptosis suppressor protein 1, identified as a ferroptosis resistance factor parallel to the glutathione peroxidase 4 pathway, have expanded and deepened our understanding of the mechanism by which ferroptosis works. Ferroptosis has been reported in spinal cord injury animal model experiments, and the inhibition of ferroptosis could promote the recovery of neurological function. Here, we review the latest studies on mechanism by which ferroptosis occurs, focusing on the ferroptosis execution and the contents related to selenium and ferroptosis suppressor protein 1. In addition, we summarize the current research status of ferroptosis in spinal cord injury. The aim of this review is to better understand the mechanisms by which ferroptosis occurs and its role in the pathophysiological process of spinal cord injury, so as to provide a new idea and frame of reference for further exploration.

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“…The development of several previously promising candidate drugs for the treatment of SCI has been halted in preclinical and clinical trials owing to safety concerns [ 3 ], and the complex mechanisms of the secondary injuries induced by SCI have hitherto obstructed the discovery of novel, effective pharmacotherapies [ 4 ]. The reassessment of clinically used drugs used in other diseases for their expanded effectiveness on SCI could speed up the translation [ 5 ].…”

Section: Introductionmentioning

confidence: 99%