Metformin Protects Radiation-Induced Early Brain Injury by Reducing Inflammation and DNA Damage
Radiation-induced brain injury (RIBI) is one of the most common and fatal complications of cranial radiation therapy (CRT); however, no effective intervention is available currently. Metformin has been reported to have anti-RIBI activity as a first-line anti-diabetic drug. However, the mechanism of...
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MDPI AG
2023-04-01
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| Series: | Brain Sciences |
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| Online Access: | https://www.mdpi.com/2076-3425/13/4/645 |
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| author | Jiabao Xiang Yiming Lu Cheng Quan Yan Gao Gangqiao Zhou |
| author_facet | Jiabao Xiang Yiming Lu Cheng Quan Yan Gao Gangqiao Zhou |
| author_sort | Jiabao Xiang |
| collection | DOAJ |
| description | Radiation-induced brain injury (RIBI) is one of the most common and fatal complications of cranial radiation therapy (CRT); however, no effective intervention is available currently. Metformin has been reported to have anti-RIBI activity as a first-line anti-diabetic drug. However, the mechanism of action is unclear. An RIBI mice model and an in vitro cell model under 30 and 10 Gy <sup>60</sup>Co γ-rays exposure were established to investigate the mechanism of metformin in RIBI. The results showed that pre-treatment with metformin protects hippocampal neurogenesis in the brain of mice and improves learning and memory ability after irradiation. Further investigations revealed that metformin pretreatment reduces inflammation and decreases DNA damage in the in vitro BV2 cell line. In addition, we observed that metformin inhibits the activation of <i>IκB</i> and <i>IRF-3</i>, which are downstream components of the cGAS-STING pathway. These findings suggest that metformin might protect the brain from RIBI, at least partly, through the cGAS pathway, making it a potential therapeutic drug for RIBI. |
| first_indexed | 2024-03-11T05:11:28Z |
| format | Article |
| id | doaj.art-d8bf4229be6b4020b1d2ef8e90fabd81 |
| institution | Directory Open Access Journal |
| issn | 2076-3425 |
| language | English |
| last_indexed | 2024-03-11T05:11:28Z |
| publishDate | 2023-04-01 |
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| record_format | Article |
| series | Brain Sciences |
| spelling | doaj.art-d8bf4229be6b4020b1d2ef8e90fabd812023-11-17T18:33:05ZengMDPI AGBrain Sciences2076-34252023-04-0113464510.3390/brainsci13040645Metformin Protects Radiation-Induced Early Brain Injury by Reducing Inflammation and DNA DamageJiabao Xiang0Yiming Lu1Cheng Quan2Yan Gao3Gangqiao Zhou4Graduate Collaborative Training Base of Academy of Military Sciences, Hengyang Medical School, University of South China, Hengyang 421001, ChinaDepartment of Genetics & Integrative Omics, State Key Laboratory of Proteomics, National Center for Protein Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, ChinaDepartment of Genetics & Integrative Omics, State Key Laboratory of Proteomics, National Center for Protein Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, ChinaCenter of Cognition and Brain Science, Beijing Institute of Basic Medical Sciences, Beijing 100850, ChinaGraduate Collaborative Training Base of Academy of Military Sciences, Hengyang Medical School, University of South China, Hengyang 421001, ChinaRadiation-induced brain injury (RIBI) is one of the most common and fatal complications of cranial radiation therapy (CRT); however, no effective intervention is available currently. Metformin has been reported to have anti-RIBI activity as a first-line anti-diabetic drug. However, the mechanism of action is unclear. An RIBI mice model and an in vitro cell model under 30 and 10 Gy <sup>60</sup>Co γ-rays exposure were established to investigate the mechanism of metformin in RIBI. The results showed that pre-treatment with metformin protects hippocampal neurogenesis in the brain of mice and improves learning and memory ability after irradiation. Further investigations revealed that metformin pretreatment reduces inflammation and decreases DNA damage in the in vitro BV2 cell line. In addition, we observed that metformin inhibits the activation of <i>IκB</i> and <i>IRF-3</i>, which are downstream components of the cGAS-STING pathway. These findings suggest that metformin might protect the brain from RIBI, at least partly, through the cGAS pathway, making it a potential therapeutic drug for RIBI.https://www.mdpi.com/2076-3425/13/4/645metforminradiationradiation-induced brain injury |
| spellingShingle | Jiabao Xiang Yiming Lu Cheng Quan Yan Gao Gangqiao Zhou Metformin Protects Radiation-Induced Early Brain Injury by Reducing Inflammation and DNA Damage Brain Sciences metformin radiation radiation-induced brain injury |
| title | Metformin Protects Radiation-Induced Early Brain Injury by Reducing Inflammation and DNA Damage |
| title_full | Metformin Protects Radiation-Induced Early Brain Injury by Reducing Inflammation and DNA Damage |
| title_fullStr | Metformin Protects Radiation-Induced Early Brain Injury by Reducing Inflammation and DNA Damage |
| title_full_unstemmed | Metformin Protects Radiation-Induced Early Brain Injury by Reducing Inflammation and DNA Damage |
| title_short | Metformin Protects Radiation-Induced Early Brain Injury by Reducing Inflammation and DNA Damage |
| title_sort | metformin protects radiation induced early brain injury by reducing inflammation and dna damage |
| topic | metformin radiation radiation-induced brain injury |
| url | https://www.mdpi.com/2076-3425/13/4/645 |
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