Edaravone attenuates brain damage in rats after acute CO poisoning through inhibiting apoptosis and oxidative stress

Li, Qin; Bi, Ming Jun; Bi, Wei; Kang, Hai; Yan, Le Jing; Guo, Yunliang

doi:10.1002/tox.22052

Cited by 28 publications

(16 citation statements)

References 14 publications

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“…Notably, preventive effect of antioxidants such as vitamin supplements and N-acetylcysteine on bone loss has been reported before (29,30). It is found that Edaravone has neuroprotective influence on cerebral ischemia by increasing the basal expressions of HO-1 and Nrf-2 proteins, which are two important antioxidative stress proteins in tissues and cells (31). Additionally, Edaravone has antiapoptosis abilities.…”

Section: Discussionmentioning

confidence: 96%

Protective effect of Edaravone against hypoxia-induced cytotoxicity in osteoblasts MC3T3-E1 cells

2015

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Edaravone is a newly developed clinical medicine for the treatment of acute cerebral infarction. Reduced blood supply to bones (hypoxia) has been involved in the pathological development of osteoporosis. In this study, we investigated the effect of Edaravone and its latent mechanism on hypoxiainduced cell toxicity in MC3T3-E1 cells. Cell viability was determined by the 3-(4,5-dimethyl-thiazol-2yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Intracellular reactive oxygen species (ROS) and nitric oxide (NO) were determined by the fluorescence dyes 2 0 ,7 0 -dichlorofluorescein diacetate (DCFH-DA) and 4-amino-5-methylamino-2 0 ,7 0 -difluorofluorescein diacetate (DAF-FM DA), respectively. mRNA and proteins were determined by real-time polymerase chain reaction and Western blot analysis, respectively. Edaravone significantly restored the hypoxia-induced reduction of MC3T3-E1 cell viability and inhibited lactate dehydrogenase release. In addition, we found that Edaravone inhibits the generation of ROS and NO. Hoechst staining results indicated that the nuclear condensation characteristic of apoptosis was increased in MC3T3-E1 cells after hypoxia exposure, which was significantly suppressed by Edaravone treatment. Mechanistically, we found that Edaravone markedly reduced the expression of cleaved caspase-3 and blunted the release of cytochrome c. These findings strongly suggested that Edaravone suppresses hypoxia-induced cytotoxicity in MC3T3-E1 cells. The pleiotropic effects of Edaravone on hypoxia exposure in osteoblasts suggest potential antiosteoporosis mechanisms of Edaravone.

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Section: Discussionmentioning

confidence: 96%

Protective effect of Edaravone against hypoxia-induced cytotoxicity in osteoblasts MC3T3-E1 cells

2015

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“…Edaravone has been reported to protect lung isolated mitochondria against ROS generation and mitochondrial dysfunction induced by the toxin Paraquat (PQ) [18]. Notably, a previous study found that edaravone improves mitochondrial function and reduces apoptosis by modulating mitochondria-dependent apoptosis pathways [19]. .…”

Section: Discussionmentioning

confidence: 99%

Edaravone protects against hyperosmolarity-induced oxidative stress and apoptosis in primary human corneal epithelial cells

Liu

Zeng

et al. 2017

PLoS ONE

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An increase in the osmolarity of tears induced by excessive evaporation of the aqueous tear phase is a major pathological mechanism behind dry eye. Exposure of epithelial cells on the surface of the human eye to hyperosmolarity leads to oxidative stress, mitochondrial dysfunction, and apoptosis. Edaravone, a hydroxyl radical scavenging agent, is clinically used to reduce neuronal damage following ischemic stroke. In this study, we found that treatment with hyperosmotic media at 400 and 450 mOsM increased the levels of ROS and mitochondrial oxidative damage, which were ameliorated by edaravone treatment in a dose-dependent manner. We also found that edaravone could improve mitochondrial function in HCEpiCs by increasing the levels of ATP and mitochondrial membrane potential. MTT and LDH assays indicated that edaravone could attenuate hyperosmolarity-induced cell death. It was found that edaravone prevented apoptosis by decreasing the level of cleaved caspase-3, and attenuating the release of cytochrome C. Mechanistically, we found that edaravone augmented the expression of Nrf2 and its target genes, such as HO-1, GPx-1, and GCLC.

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“…Our previous study indicated that the significantly ultrastructural alterations occurred in brain parenchyma in rats after CO exposure, including brain edema, chromatin condensation, nucleus membrane and cell organelles decomposition, even neuronal death (Li Q. et al, 2015; Li et al, 2016). N -butylphthalide (NBP), a new drug extracted from celery seeds (see Figure 1 ), was approved by China Food and Drug Administration in 2002.…”

Section: Introductionmentioning

confidence: 99%

“…Meanwhile, NBP had also positive effects in stabilizing the NVUs and improving the neurological deficits through its primary target vascular endothelium (Li et al, 2007; Thored et al, 2007). Besides, the application of NBP could inhibit neuronal apoptosis, and attenuate brain parenchymal injury induced by CO poisoning (Li et al, 2016). Nevertheless, the effects of NBP on the ultrastructural integrity and on the BBB after CO poisoning are still unknown.…”

Section: Introductionmentioning

confidence: 99%

N-Butylphthalide Alleviates Blood–Brain Barrier Impairment in Rats Exposed to Carbon Monoxide

Zhang

Guo

et al. 2016

Front. Pharmacol.

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Carbon monoxide (CO) poisoning is one of the most important health concerns and may result in neuropathologic changes and neurologic sequelae. However, few studies have addressed the correlation between CO poisoning and blood–brain barrier (BBB) impairment. In this study, we investigated the effects of N-butylphthalide (NBP) on the expressions of zonula occludens-1 (ZO-1), claudin-5 and aquaporin-4 (AQP-4) proteins in a CO poisoning rat model. The results indicated that the brain water content was obviously increased, and the tight junctions between endothelial cells were disrupted, resulting in significant cerebral edema and BBB dysfunction in a rat model of CO poisoning. Meanwhile, the ultrastructure of endothelial cells and pericytes was seriously damaged, and the expressions of ZO-1 and claudin-5 were decreased at an early stage (<7 days). NBP treatment could efficiently maintain the ultrastructural and functional integrity of BBB, alleviate cerebral edema. Besides, NBP could also markedly increase the levels of both ZO-1 and claudin-5 proteins compared with those in rats exposed to CO (P < 0.05), whereas NBP had no apparent regulatory effect on AQP-4 expression. Taken together, this study highlights the importance of ZO-1 and claudin-5 proteins in maintaining BBB ultrastructure and function after CO poisoning. NBP, as a novel treatment approach, may effectively inhibit the down-regulation of ZO-1 and claudin-5 proteins (but not AQP-4), thereby preserving the barrier function and reducing cerebral edema after CO poisoning.

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Edaravone attenuates brain damage in rats after acute CO poisoning through inhibiting apoptosis and oxidative stress

Cited by 28 publications

References 14 publications

Protective effect of Edaravone against hypoxia-induced cytotoxicity in osteoblasts MC3T3-E1 cells

Protective effect of Edaravone against hypoxia-induced cytotoxicity in osteoblasts MC3T3-E1 cells

Edaravone protects against hyperosmolarity-induced oxidative stress and apoptosis in primary human corneal epithelial cells

N-Butylphthalide Alleviates Blood–Brain Barrier Impairment in Rats Exposed to Carbon Monoxide

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