Edaravone prevents high glucose-induced injury in retinal Müller cells through thioredoxin1 and the PGC-1α/NRF1/TFAM pathway
Context Oxidative injury in a high-glucose (HG) environment may be a mechanism of diabetic retinopathy (DR) and edaravone can protect retinal ganglion cells by scavenging ROS. Objective To explore the effect of edaravone on HG-induced injury. Materials and methods First, Müller cells were cultured b...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2021-01-01
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| Series: | Pharmaceutical Biology |
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| Online Access: | http://dx.doi.org/10.1080/13880209.2021.1972123 |
| _version_ | 1818663566991949824 |
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| author | Juanping Yin Xinke Chen |
| author_facet | Juanping Yin Xinke Chen |
| author_sort | Juanping Yin |
| collection | DOAJ |
| description | Context Oxidative injury in a high-glucose (HG) environment may be a mechanism of diabetic retinopathy (DR) and edaravone can protect retinal ganglion cells by scavenging ROS. Objective To explore the effect of edaravone on HG-induced injury. Materials and methods First, Müller cells were cultured by different concentrations of glucose for different durations to obtain a suitable culture concentrations and duration. Müller cells were then divided into Control, HG + Vehicle, HG + Eda-5 μM, HG + Eda-10 μM, HG + Eda-20 μM, and HG + Eda-40 μM groups. Cells were cultured by 20 mM glucose and different concentrations of edaravone for 72 h. Results The IC50 of glucose at 12–72 h is 489.3, 103.5, 27.92 and 20.71 mM, respectively. When Müller cells were cultured in 20 mM glucose for 72 h, the cell viability was 52.3%. Edaravone significantly increased cell viability compared to Vehicle (68.4% vs 53.3%; 78.6% vs 53.3%). The EC50 of edaravone is 34.38 μM. HG induced high apoptosis rate (25.5%), while edaravone (20 and 40 μM) reduced it to 12.5% and 6.89%. HG increased the DCF fluorescence signal (189% of Control) and decreased the mitochondrial membrane potential by 57%. Edaravone significantly decreased the DCF fluorescence signal (144% and 132% of Control) and recovered the mitochondrial membrane potential to 68% and 89% of Control. Furthermore, HG decreased the expression of TRX1, PGC-1α, NRF1 and TFAM, which were restored by edaravone. Discussion and conclusion These findings provide a new potential approach for the treatment of DR and indicated new molecular targets in the prevention of DR. |
| first_indexed | 2024-12-17T05:18:54Z |
| format | Article |
| id | doaj.art-4d065cbab9784859bdfff4f79abbf7bb |
| institution | Directory Open Access Journal |
| issn | 1388-0209 1744-5116 |
| language | English |
| last_indexed | 2024-12-17T05:18:54Z |
| publishDate | 2021-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Pharmaceutical Biology |
| spelling | doaj.art-4d065cbab9784859bdfff4f79abbf7bb2022-12-21T22:02:01ZengTaylor & Francis GroupPharmaceutical Biology1388-02091744-51162021-01-015911233124410.1080/13880209.2021.19721231972123Edaravone prevents high glucose-induced injury in retinal Müller cells through thioredoxin1 and the PGC-1α/NRF1/TFAM pathwayJuanping Yin0Xinke Chen1Department of Ophthalmology, The Fourth Hospital of Changsha, Changsha Hospital of Hunan Normal UniversityDepartment of Ophthalmology, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and DisordersContext Oxidative injury in a high-glucose (HG) environment may be a mechanism of diabetic retinopathy (DR) and edaravone can protect retinal ganglion cells by scavenging ROS. Objective To explore the effect of edaravone on HG-induced injury. Materials and methods First, Müller cells were cultured by different concentrations of glucose for different durations to obtain a suitable culture concentrations and duration. Müller cells were then divided into Control, HG + Vehicle, HG + Eda-5 μM, HG + Eda-10 μM, HG + Eda-20 μM, and HG + Eda-40 μM groups. Cells were cultured by 20 mM glucose and different concentrations of edaravone for 72 h. Results The IC50 of glucose at 12–72 h is 489.3, 103.5, 27.92 and 20.71 mM, respectively. When Müller cells were cultured in 20 mM glucose for 72 h, the cell viability was 52.3%. Edaravone significantly increased cell viability compared to Vehicle (68.4% vs 53.3%; 78.6% vs 53.3%). The EC50 of edaravone is 34.38 μM. HG induced high apoptosis rate (25.5%), while edaravone (20 and 40 μM) reduced it to 12.5% and 6.89%. HG increased the DCF fluorescence signal (189% of Control) and decreased the mitochondrial membrane potential by 57%. Edaravone significantly decreased the DCF fluorescence signal (144% and 132% of Control) and recovered the mitochondrial membrane potential to 68% and 89% of Control. Furthermore, HG decreased the expression of TRX1, PGC-1α, NRF1 and TFAM, which were restored by edaravone. Discussion and conclusion These findings provide a new potential approach for the treatment of DR and indicated new molecular targets in the prevention of DR.http://dx.doi.org/10.1080/13880209.2021.1972123diabetesretinarosantioxidantapoptosismitochondrial membrane potentialoxidative productsantioxidative enzymes |
| spellingShingle | Juanping Yin Xinke Chen Edaravone prevents high glucose-induced injury in retinal Müller cells through thioredoxin1 and the PGC-1α/NRF1/TFAM pathway Pharmaceutical Biology diabetes retina ros antioxidant apoptosis mitochondrial membrane potential oxidative products antioxidative enzymes |
| title | Edaravone prevents high glucose-induced injury in retinal Müller cells through thioredoxin1 and the PGC-1α/NRF1/TFAM pathway |
| title_full | Edaravone prevents high glucose-induced injury in retinal Müller cells through thioredoxin1 and the PGC-1α/NRF1/TFAM pathway |
| title_fullStr | Edaravone prevents high glucose-induced injury in retinal Müller cells through thioredoxin1 and the PGC-1α/NRF1/TFAM pathway |
| title_full_unstemmed | Edaravone prevents high glucose-induced injury in retinal Müller cells through thioredoxin1 and the PGC-1α/NRF1/TFAM pathway |
| title_short | Edaravone prevents high glucose-induced injury in retinal Müller cells through thioredoxin1 and the PGC-1α/NRF1/TFAM pathway |
| title_sort | edaravone prevents high glucose induced injury in retinal muller cells through thioredoxin1 and the pgc 1α nrf1 tfam pathway |
| topic | diabetes retina ros antioxidant apoptosis mitochondrial membrane potential oxidative products antioxidative enzymes |
| url | http://dx.doi.org/10.1080/13880209.2021.1972123 |
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