Edaravone attenuates oxidative stress induced by chronic cerebral hypoperfusion injury: role of ERK/Nrf2/HO-1 signaling pathway

Zhang, Dandan; Xiao, Yining; Lv, Peiyuan; Teng, Zhenjie; Dong, Yanhong; Qi, Qianqian; Liu, Zhijuan

doi:10.1080/01616412.2017.1376457

Cited by 59 publications

(31 citation statements)

References 40 publications

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“…The results of oxidative stress and antioxidative enzymes in the present study indicated that Eda may alleviate the severity of asthma by suppressing oxidative injury and restoring the antioxidative enzyme, SOD. It has been shown that Eda may exert a protective effect through the Nrf2/HO-1 pathway (28)(29)(30). Li et al (57) revealed that Eda protects against hyperosmolarity-induced oxidative stress and apoptosis in primary human corneal epithelial cells by increasing the expression of Nrf2 and its target genes, such as HO-1 and GPx-1.…”

Section: Discussionmentioning

confidence: 99%

“…Zhang et al (28) revealed that Eda reduced iron-mediated hydrocephalus and behavioral disorders in rats through Nrf2/HO-1 activation. In an animal model of cognitive damage induced by chronic cerebral hypoperfusion (CCH), Eda reduced CCH-induced cognitive damage and increased SOD activity and HO-1 levels, but decreased MDA levels in the hippocampus through activation of the Nrf2 pathway (29). Liu et al (30) found that Eda increased neuronal density and decreased neuronal damage induced by kainite, which was administrated in the right hippocampus CA3 region using the sereotactic technique and this enhanced the expression of Nrf2 and HO-1.…”

Section: Edaravone Attenuates Experimental Asthma In Mice Through Indmentioning

confidence: 99%

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Edaravone attenuates experimental asthma in mice through induction of HO‑1 and the Keap1/Nrf2 pathway

Pan

Feng

et al. 2019

Exp Ther Med

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Asthma is a chronic disease that threatens public health worldwide. Multiple studies have shown that oxidative stress plays an important role in the pathogenesis of asthma. Edaravone (Eda), a free radical scavenger, has been found to have a protective effect against lung injury due to its ability to eliminate reactive oxygen species. The present study aimed to investigate the effect of Eda on asthma and the mechanism underlying its actions. An experimental asthma model was induced in mice, before they were treated with different doses of Eda. Measurements of airway responsiveness to methacholine (Mch), cell counts and cytokine levels in bronchoalveolar lavage fluid (BALF) and of the oxidative products and antioxidant enzymes in lung tissue were taken in these asthma model mice and compared with control mice. Protein levels of kelch-like ECH-associated protein-1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) and hemeoxygenase-1 (HO-1) were determined in the lung tissue of normal mice and Nrf2 and HO-1-deficient mice subject to the asthma model to investigate the mechanisms underlying Eda action. The results indicated that Eda effectively reduced airway responsiveness to Mch. The total number of cells and the numbers of eosinophils, lymphocytes and neutrophils in BALF of asthma model mice were also significantly reduced by Eda treatment when compared with normal saline treatment. Eda treatment significantly alleviated perivascular edema, peribronchial inflammation and macrophage infiltration in the alveolar space and decreased the levels of inflammatory cytokines released in BALF compared with control. Eda also significantly reduced the levels of oxidative stress markers in BALF and restored the levels of antioxidative enzyme, superoxide dismutase, when compared with control. The Keap1/Nrf2 ratio was significantly decreased with Eda compared with control due to an increase in Nrf2 and a decrease in Keap1 expression. HO-1 expression was increased by Eda. The airway responsiveness of Nrf2-/mice or HO-1-/mice to Mch was significantly higher compared with normal mice treated with Eda. Taken together, the results of the present study show that Eda exerts anti-inflammatory and antioxidative effects, which suggests a potential use for Eda in reduction of asthma severity. The activated Keap1/Nrf2 pathway and HO-1 may be involved in the anti-asthmatic effect of Eda.

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Section: Discussionmentioning

confidence: 99%

Section: Edaravone Attenuates Experimental Asthma In Mice Through Indmentioning

confidence: 99%

Edaravone attenuates experimental asthma in mice through induction of HO‑1 and the Keap1/Nrf2 pathway

Pan

Feng

et al. 2019

Exp Ther Med

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“…Stroke is defined by sudden interruption of the local blood supply and by initiation of an anoxic and hypoglycemic state in the affected brain tissue. Under this condition, neuronal depolarization leads to the release of the neurotransmitter glutamate, which is the activator of the ionotropic NMDA receptor, resulting in Ca 2+ overload and excessive ROS production by mitochondria [ 98 , 99 , 100 , 101 , 102 ]. Furthermore, degradation of structural proteins of the vascular wall and loss of brain–blood barrier (BBB) integrity further enhance tissue oxygenation, which exacerbates ROS production.…”

Section: Nrf2 Mitochondrial Dynamics and Mitophagy In Neurologicmentioning

confidence: 99%

“…Furthermore, degradation of structural proteins of the vascular wall and loss of brain–blood barrier (BBB) integrity further enhance tissue oxygenation, which exacerbates ROS production. Although there are few studies on the alterations of the Nrf2 system in human patient specimens, Nrf2 pathway activators up-regulate the expression of tight junctional proteins (TJ) and promote redox metabolic functions and ATP synthesis with mitochondrial biogenesis, which protect neurons from stroke in animal models [ 98 , 99 , 100 , 101 , 102 , 103 , 104 ].…”

Section: Nrf2 Mitochondrial Dynamics and Mitophagy In Neurologicmentioning

confidence: 99%

Nuclear Factor-Erythroid 2-Related Factor 2 (Nrf2) and Mitochondrial Dynamics/Mitophagy in Neurological Diseases

Kang

2020

Antioxidants

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Mitochondria play an essential role in bioenergetics and respiratory functions for cell viability through numerous biochemical processes. To maintain mitochondria quality control and homeostasis, mitochondrial morphologies change rapidly in response to external insults and changes in metabolic status through fusion and fission (so called mitochondrial dynamics). Furthermore, damaged mitochondria are removed via a selective autophagosomal process, referred to as mitophagy. Although mitochondria are one of the sources of reactive oxygen species (ROS), they are themselves vulnerable to oxidative stress. Thus, endogenous antioxidant defense systems play an important role in cell survival under physiological and pathological conditions. Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a redox-sensitive transcription factor that maintains redox homeostasis by regulating antioxidant-response element (ARE)-dependent transcription and the expression of antioxidant defense enzymes. Although the Nrf2 system is positively associated with mitochondrial biogenesis and mitochondrial quality control, the relationship between Nrf2 signaling and mitochondrial dynamics/mitophagy has not been sufficiently addressed in the literature. This review article describes recent clinical and experimental observations on the relationship between Nrf2 and mitochondrial dynamics/mitophagy in various neurological diseases.

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“…Currently, the underlying mechanisms of VD have been linked to hippocampus neuron damage, inflammatory response, and oxidative stress ( Jiwa et al, 2010 ; Zhang et al, 2018 ). Furthermore, BCCAO-induced cognitive impairment and the occurrence of VD-like pathogenesis characterized by the deposition of beta-amyloid (Aβ) in the hippocampus are found ( Cai et al, 2017 ), and emerging strategies for interfering with the metabolism of Aβ might be promising therapeutic approaches to attenuate or reverse negative neurological consequences of BCCAO ( Won et al, 2013 ; Zhu et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Gastrodin Attenuates Bilateral Common Carotid Artery Occlusion-Induced Cognitive Deficits via Regulating Aβ-Related Proteins and Reducing Autophagy and Apoptosis in Rats

Liu

Gao

et al. 2018

Front. Pharmacol.

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Gastrodin (GAS), an active constituent extracted from Gastrodia elata Blume, is used to treat ischemic stroke, epilepsy, dizziness, and dementia for centuries in China. This study examined its effects on vascular dementia (VD) and the underlying molecular mechanisms. VD was established by ligation of bilateral common carotid artery occlusion (BCCAO). A total of 7 days after BCCAO surgery, GAS (15, 30, and 60 mg/kg) was orally administered for 28 consecutive days to evaluate therapeutic effects. Cognitive function was tested by the Morris water maze. The neuronal morphological changes were examined via Hematoxylin–Eosin staining. Flow cytometry was used for evaluating apoptosis in the hippocampi. The target protein expression was examined by Western blot. The results showed that BCCAO induced cognitive impairment, hippocampus CA1 and CA3 pyramidal neuron damage, beta-amyloid (Aβ) deposition, excessive autophagy, and apoptosis. GAS treatment significantly improved BCCAO-induced cognitive deficits and hippocampus neuron damage. Molecular analysis revealed that GAS exerted the protective effect via reducing the levels of Aβ1–40/42, APP, and β-site APP-cleaving enzyme 1 expression, and increasing Aβ-related protein, a disintegrin and metalloprotease 10, and insulin degrading enzyme expression. Meanwhile, GAS inhibited excessive autophagy via decreasing Beclin-1, LC3-II, and p62 levels. Furthermore, GAS inhibited apoptosis through the downregulation of Bax and upregulation of Bcl-2. Moreover, P38 MAPK signaling pathway was involved in the process. Our findings demonstrate that GAS was effective in the treatment of BCCAO-induced VD via targeting Aβ-related protein formation and inhibiting autophagy and apoptosis of hippocampus neurons.

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Edaravone attenuates oxidative stress induced by chronic cerebral hypoperfusion injury: role of ERK/Nrf2/HO-1 signaling pathway

Cited by 59 publications

References 40 publications

Edaravone attenuates experimental asthma in mice through induction of HO‑1 and the Keap1/Nrf2 pathway

Edaravone attenuates experimental asthma in mice through induction of HO‑1 and the Keap1/Nrf2 pathway

Nuclear Factor-Erythroid 2-Related Factor 2 (Nrf2) and Mitochondrial Dynamics/Mitophagy in Neurological Diseases

Gastrodin Attenuates Bilateral Common Carotid Artery Occlusion-Induced Cognitive Deficits via Regulating Aβ-Related Proteins and Reducing Autophagy and Apoptosis in Rats

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