Deferoxamine therapy for intracerebral hemorrhage: A systematic review

Zeng, Liling; Tan, Li; Li, Haijun; Zhang, Qixin; Li, Yongxian; Guo, Jianwen

doi:10.1371/journal.pone.0193615

Cited by 36 publications

(32 citation statements)

References 38 publications

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“…Various evidence has shown that iron chelators reduce Hb- and iron-induced neurotoxicity attenuates brain edema, and improve functional neurologic outcomes after ICH ( Nakamura et al, 2004 ; Wu et al, 2012 ; Hatakeyama et al, 2013 ). A meta-analysis of 20 studies involving animal models of ICH revealed that DFO was neuroprotective, particularly when administered 2–4 h after ICH induction ( Cui et al, 2015 ), whereas there remains a lack of conclusive clinical evidence regarding iron chelators ( Zeng et al, 2018 ).…”

Section: Potential and Emerging Therapy Targeting Ferroptosis In Acutmentioning

confidence: 99%

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: Potential and Emerging Therapy Targeting Ferroptosis In Acutmentioning

confidence: 99%

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

Shen

Lin

et al. 2020

Front. Cell Dev. Biol.

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“…A systematic review and meta-analysis in experimental models of ICH showed that DFO was neuroprotective, e.g., reduction of brain edema and improvement of neurobehavioral outcomes, especially when it was administered 2-4 h after ICH induction (Cui et al, 2015). In clinical studies, conclusive evidence of the benefit of DFO treatment in ICH (Zeng et al, 2018) or AIS patients is still lacking; some clinical trials of DFO in ICH and AIS are currently ongoing.…”

Section: The Ferroptotic Component Of Stroke-induced Neurodegenerationmentioning

confidence: 99%

Deciphering the Iron Side of Stroke: Neurodegeneration at the Crossroads Between Iron Dyshomeostasis, Excitotoxicity, and Ferroptosis

DeGregorio-Rocasolano

2019

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In general, iron represents a double-edged sword in metabolism in most tissues, especially in the brain. Although the high metabolic demands of brain cells require iron as a redox-active metal for ATP-producing enzymes, the brain is highly vulnerable to the devastating consequences of excessive iron-induced oxidative stress and, as recently found, to ferroptosis as well. The blood–brain barrier (BBB) protects the brain from fluctuations in systemic iron. Under pathological conditions, especially in acute brain pathologies such as stroke, the BBB is disrupted, and iron pools from the blood gain sudden access to the brain parenchyma, which is crucial in mediating stroke-induced neurodegeneration. Each brain cell type reacts with changes in their expression of proteins involved in iron uptake, efflux, storage, and mobilization to preserve its internal iron homeostasis, with specific organelles such as mitochondria showing specialized responses. However, during ischemia, neurons are challenged with excess extracellular glutamate in the presence of high levels of extracellular iron; this causes glutamate receptor overactivation that boosts neuronal iron uptake and a subsequent overproduction of membrane peroxides. This glutamate-driven neuronal death can be attenuated by iron-chelating compounds or free radical scavenger molecules. Moreover, vascular wall rupture in hemorrhagic stroke results in the accumulation and lysis of iron-rich red blood cells at the brain parenchyma and the subsequent presence of hemoglobin and heme iron at the extracellular milieu, thereby contributing to iron-induced lipid peroxidation and cell death. This review summarizes recent progresses made in understanding the ferroptosis component underlying both ischemic and hemorrhagic stroke subtypes.

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“…This finding can be related with the capacity of DFX to cross the BBB and chelate iron ions (Keberle, ), reducing the metal accumulation in the nervous system (Hwang et al., ; Palmer, Roberts, & Bero, ). Thus, through this mechanism, DFX plays a neuroprotective role, and it could be used in the treatment of intracerebral hemorrhage (Selim, ; Zeng et al., ).…”

Section: Discussionmentioning

confidence: 99%

Deferoxamine pretreatment inhibits metal neurotoxicity in Caenorhabditis elegans

Alves

Zancan

Concato

et al. 2019

Environmental Quality Mgmt

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Neurodegenerative diseases are increasingly common in humans. Alzheimer's disease (AD) is a neurodegenerative disease characterized by the presence of extracellular plaques containing -amyloid peptides and neurofibrillary tangles in the brains. Researchers have focused on the elucidation of a correlation between high concentrations of aluminum or iron (in the organism with observed neuropathology). The objective of this study was to evaluate the effects of aluminum and iron on the behavioral parameters (pharyngeal pumping and defecation cycle) of the nematode Caenorhabditis elegans pretreated with deferoxamine (DFX). Acetylcholinesterase (AChE) activity was evaluated as well. DFX is a chelant that is widely used for the treatment of metal toxicity, and it has a high affinity for aluminum and iron. The worms were pretreated with DFX, and then exposed to aluminum and iron. In the absence of DFX, aluminum exposure decreased pharyngeal pumping compared with that in the control group. The defecation cycle of the control was significantly different from that of the worms exposed to aluminum. In contrast, an increased defecation cycle was observed in worms exposed to iron without DFX pretreatment. AChE activity increased in aluminum-exposed groups that received DFX pretreatment compared with those that did not receive pretreatment. These results suggest that pretreatment with DFX is effective in reducing metal toxicity, particularly with reference to AChE activity, which did not decrease in groups that did not receive DFX pretreatment. K E Y W O R D Saluminum, chelate therapy, cholinergic system, iron, worms

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Deferoxamine therapy for intracerebral hemorrhage: A systematic review

Cited by 36 publications

References 38 publications

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

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

Deciphering the Iron Side of Stroke: Neurodegeneration at the Crossroads Between Iron Dyshomeostasis, Excitotoxicity, and Ferroptosis

Deferoxamine pretreatment inhibits metal neurotoxicity in Caenorhabditis elegans

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