Protective effects of phenformin on zebrafish embryonic neurodevelopmental toxicity induced by X-ray radiation
Radiotherapy (RT) is a common treatment for head and neck cancers, but central nervous system function can be impaired by clinical radiation doses. This experimental study evaluated the protective efficacy of the anti-hyperglycaemic/anti-neoplastic agent phenformin against radiation-induced developm...
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Taylor & Francis Group
2019-12-01
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| Series: | Artificial Cells, Nanomedicine, and Biotechnology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/21691401.2019.1687505 |
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| author | Lu Gan Menghuan Guo Jing Si Jinhua Zhang Zhiyuan Liu Jin Zhao Fang Wang Junfang Yan Hongyan Li Hong Zhang |
| author_facet | Lu Gan Menghuan Guo Jing Si Jinhua Zhang Zhiyuan Liu Jin Zhao Fang Wang Junfang Yan Hongyan Li Hong Zhang |
| author_sort | Lu Gan |
| collection | DOAJ |
| description | Radiotherapy (RT) is a common treatment for head and neck cancers, but central nervous system function can be impaired by clinical radiation doses. This experimental study evaluated the protective efficacy of the anti-hyperglycaemic/anti-neoplastic agent phenformin against radiation-induced developmental toxicity in zebrafish embryos. Zebrafish embryos pre-treated with 25 μM phenformin 1 h before x-ray irradiation were compared to irradiation-only embryos for mortality, hatching rate, morphology, spontaneous movement, heart beat, larval swimming, activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), malondialdehyde content (MDA, a by-product of membrane lipid oxidation), and acetylcholinesterase (AChE) activity. In addition, expression levels of multiple genes related to neural development and apoptosis (sod2, bdnf, ache, p53, bax, and bcl-2) were compared by RT-PCR and associated protein expression levels by western blotting. Pre-treatment with phenformin increased hatching rate, spontaneous movement, heart beat, and larval motor activity, decreased mortality and malformation rate, increased SOD, CAT, and AChE activities, and reduced MDA compared to irradiation-only embryos. The mRNA expression levels of anti-apoptotic sod2, bdnf, ache, and bcl-2 were enhanced while mRNA expression of p53 and pro-apoptotic bax were reduced in the phenformin pre-treatment group. Further, p53, Bax, and γ-H2AX (a biomarker of DNA damage) were downregulated while Bcl-2 and BDNF were upregulated by phenformin pre-treatment. Taken together, this study supports the protective efficacy of phenformin against radiation toxicity in zebrafish embryos by suppressing oxidative stress and ensuing apoptosis. |
| format | Article |
| id | doaj-art-11d3b95f00b94306b0069e88aa1cb6a8 |
| institution | Matheson Library |
| issn | 2169-1401 2169-141X |
| language | English |
| publishDate | 2019-12-01 |
| publisher | Taylor & Francis Group |
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| series | Artificial Cells, Nanomedicine, and Biotechnology |
| spelling | doaj-art-11d3b95f00b94306b0069e88aa1cb6a82025-07-21T21:20:27ZengTaylor & Francis GroupArtificial Cells, Nanomedicine, and Biotechnology2169-14012169-141X2019-12-014714202421010.1080/21691401.2019.1687505Protective effects of phenformin on zebrafish embryonic neurodevelopmental toxicity induced by X-ray radiationLu Gan0Menghuan Guo1Jing Si2Jinhua Zhang3Zhiyuan Liu4Jin Zhao5Fang Wang6Junfang Yan7Hongyan Li8Hong Zhang9Department of Radiation Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, ChinaSchool of Pharmacy, Lanzhou University, Lanzhou, ChinaDepartment of Radiation Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, ChinaDepartment of Radiation Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, ChinaCollege of Chemical Engineering, Northwest Minzu University, Lanzhou, ChinaMedical College of Northwest Minzu University, Lanzhou, ChinaDepartment of Radiation Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, ChinaDepartment of Radiation Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, ChinaDepartment of Radiation Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, ChinaDepartment of Radiation Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, ChinaRadiotherapy (RT) is a common treatment for head and neck cancers, but central nervous system function can be impaired by clinical radiation doses. This experimental study evaluated the protective efficacy of the anti-hyperglycaemic/anti-neoplastic agent phenformin against radiation-induced developmental toxicity in zebrafish embryos. Zebrafish embryos pre-treated with 25 μM phenformin 1 h before x-ray irradiation were compared to irradiation-only embryos for mortality, hatching rate, morphology, spontaneous movement, heart beat, larval swimming, activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), malondialdehyde content (MDA, a by-product of membrane lipid oxidation), and acetylcholinesterase (AChE) activity. In addition, expression levels of multiple genes related to neural development and apoptosis (sod2, bdnf, ache, p53, bax, and bcl-2) were compared by RT-PCR and associated protein expression levels by western blotting. Pre-treatment with phenformin increased hatching rate, spontaneous movement, heart beat, and larval motor activity, decreased mortality and malformation rate, increased SOD, CAT, and AChE activities, and reduced MDA compared to irradiation-only embryos. The mRNA expression levels of anti-apoptotic sod2, bdnf, ache, and bcl-2 were enhanced while mRNA expression of p53 and pro-apoptotic bax were reduced in the phenformin pre-treatment group. Further, p53, Bax, and γ-H2AX (a biomarker of DNA damage) were downregulated while Bcl-2 and BDNF were upregulated by phenformin pre-treatment. Taken together, this study supports the protective efficacy of phenformin against radiation toxicity in zebrafish embryos by suppressing oxidative stress and ensuing apoptosis.https://www.tandfonline.com/doi/10.1080/21691401.2019.1687505X-ray irradiationzebrafishphenforminneurodevelopmental protective effects |
| spellingShingle | Lu Gan Menghuan Guo Jing Si Jinhua Zhang Zhiyuan Liu Jin Zhao Fang Wang Junfang Yan Hongyan Li Hong Zhang Protective effects of phenformin on zebrafish embryonic neurodevelopmental toxicity induced by X-ray radiation Artificial Cells, Nanomedicine, and Biotechnology X-ray irradiation zebrafish phenformin neurodevelopmental protective effects |
| title | Protective effects of phenformin on zebrafish embryonic neurodevelopmental toxicity induced by X-ray radiation |
| title_full | Protective effects of phenformin on zebrafish embryonic neurodevelopmental toxicity induced by X-ray radiation |
| title_fullStr | Protective effects of phenformin on zebrafish embryonic neurodevelopmental toxicity induced by X-ray radiation |
| title_full_unstemmed | Protective effects of phenformin on zebrafish embryonic neurodevelopmental toxicity induced by X-ray radiation |
| title_short | Protective effects of phenformin on zebrafish embryonic neurodevelopmental toxicity induced by X-ray radiation |
| title_sort | protective effects of phenformin on zebrafish embryonic neurodevelopmental toxicity induced by x ray radiation |
| topic | X-ray irradiation zebrafish phenformin neurodevelopmental protective effects |
| url | https://www.tandfonline.com/doi/10.1080/21691401.2019.1687505 |
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