Astilbin antagonizes developmental cardiotoxicity after cadmium exposure in chicken embryos by inhibiting endoplasmic reticulum stress and maintaining calcium homeostasis
Cadmium (Cd) is a dangerous heavy metal with high toxicity that is known to impair development. Astilbin (ASB) is a protective flavonoid compound. We aimed to explore whether ASB can antagonize the myocardial developmental toxicity of Cd exposure. Cd (2 µg) and/or ASB (0.002 µg) were injected into e...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-01-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651323013519 |
| _version_ | 1797350578211258368 |
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| author | Yue Zhu Haoyue Guan Xingxi Zhu Jingzeng Cai Xing Jiao Jianhua Shan Yangyang Li Qiong Wu Ziwei Zhang |
| author_facet | Yue Zhu Haoyue Guan Xingxi Zhu Jingzeng Cai Xing Jiao Jianhua Shan Yangyang Li Qiong Wu Ziwei Zhang |
| author_sort | Yue Zhu |
| collection | DOAJ |
| description | Cadmium (Cd) is a dangerous heavy metal with high toxicity that is known to impair development. Astilbin (ASB) is a protective flavonoid compound. We aimed to explore whether ASB can antagonize the myocardial developmental toxicity of Cd exposure. Cd (2 µg) and/or ASB (0.002 µg) were injected into embryonized eggs that were 1 day old. Histological examinations revealed Cd-induced ventricular dilation, reduced wall thickness, and disrupted myocardial fiber connections, while co-administration of ASB mitigated these effects. Electron microscopy confirmed ASB's ability to counteract Cd-induced myocardial cell myofibril damage. Real-time quantitative PCR (QRT-PCR) and western blot (WB) molecular investigations revealed that Cd increased endoplasmic reticulum stress in myocardial tissue and primary cardiomyocytes, as shown by raised expression of stress-related genes (GRP78, XBP1, GRP94, ATF4, ATF6, IRE1, and CHOP). Moreover, Cd disrupted calcium homeostasis, affecting important genes linked to Ca2+ channels and causing an excess of Ca2+ in the cytoplasm. In addition, we detected genes related to development and differentiation-related genes in myocardial tissue and primary cardiomyocytes. The results showed that the downregulation of transcription factors in the IrxA cluster, Mefs, and Tbxs families after Cd exposure indicated that cardiac transcription was hindered and cardiac markers (TnnT2, TnnC1, Gata4, Gata6, and Nkx2–5) were abnormally expressed. ASB successfully mitigated these disturbances. During the cell cycle, primary cardiomyocytes undergo growth arrest in flow cytometry. These results suggest that the maturation and differentiation of cardiomyocytes are inhibited after Cd exposure, and ASB has an antagonistic effect on Cd. The present study indicated that Cd could trigger developmental cardiotoxicity in chicken embryos and primary cardiomyocytes by endoplasmic reticulum stress and Ca2+ overload, respectively, while ASB has an antagonistic effect. |
| first_indexed | 2024-03-08T12:47:57Z |
| format | Article |
| id | doaj.art-09325838ffe948debd61c14f1ff276f3 |
| institution | Directory Open Access Journal |
| issn | 0147-6513 |
| language | English |
| last_indexed | 2024-03-08T12:47:57Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj.art-09325838ffe948debd61c14f1ff276f32024-01-21T05:04:59ZengElsevierEcotoxicology and Environmental Safety0147-65132024-01-01270115847Astilbin antagonizes developmental cardiotoxicity after cadmium exposure in chicken embryos by inhibiting endoplasmic reticulum stress and maintaining calcium homeostasisYue Zhu0Haoyue Guan1Xingxi Zhu2Jingzeng Cai3Xing Jiao4Jianhua Shan5Yangyang Li6Qiong Wu7Ziwei Zhang8College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR ChinaCollege of Animal Science and Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, PR ChinaMacao Polytechnic University, Macao 999078, PR ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China; Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, PR ChinaChina Institute of Water Resources and Hydropower Research, Beijing 100038, PR ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR ChinaChina Agricultural University, Beijing 10000, PR ChinaAnimal Science and Technology College, Beijing University of Agriculture, Beijing 100096, PR ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China; Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, PR China; Corresponding author at: College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China.Cadmium (Cd) is a dangerous heavy metal with high toxicity that is known to impair development. Astilbin (ASB) is a protective flavonoid compound. We aimed to explore whether ASB can antagonize the myocardial developmental toxicity of Cd exposure. Cd (2 µg) and/or ASB (0.002 µg) were injected into embryonized eggs that were 1 day old. Histological examinations revealed Cd-induced ventricular dilation, reduced wall thickness, and disrupted myocardial fiber connections, while co-administration of ASB mitigated these effects. Electron microscopy confirmed ASB's ability to counteract Cd-induced myocardial cell myofibril damage. Real-time quantitative PCR (QRT-PCR) and western blot (WB) molecular investigations revealed that Cd increased endoplasmic reticulum stress in myocardial tissue and primary cardiomyocytes, as shown by raised expression of stress-related genes (GRP78, XBP1, GRP94, ATF4, ATF6, IRE1, and CHOP). Moreover, Cd disrupted calcium homeostasis, affecting important genes linked to Ca2+ channels and causing an excess of Ca2+ in the cytoplasm. In addition, we detected genes related to development and differentiation-related genes in myocardial tissue and primary cardiomyocytes. The results showed that the downregulation of transcription factors in the IrxA cluster, Mefs, and Tbxs families after Cd exposure indicated that cardiac transcription was hindered and cardiac markers (TnnT2, TnnC1, Gata4, Gata6, and Nkx2–5) were abnormally expressed. ASB successfully mitigated these disturbances. During the cell cycle, primary cardiomyocytes undergo growth arrest in flow cytometry. These results suggest that the maturation and differentiation of cardiomyocytes are inhibited after Cd exposure, and ASB has an antagonistic effect on Cd. The present study indicated that Cd could trigger developmental cardiotoxicity in chicken embryos and primary cardiomyocytes by endoplasmic reticulum stress and Ca2+ overload, respectively, while ASB has an antagonistic effect.http://www.sciencedirect.com/science/article/pii/S0147651323013519CadmiumFlavonoidsMyocardiumDevelopmentChicken Embryos |
| spellingShingle | Yue Zhu Haoyue Guan Xingxi Zhu Jingzeng Cai Xing Jiao Jianhua Shan Yangyang Li Qiong Wu Ziwei Zhang Astilbin antagonizes developmental cardiotoxicity after cadmium exposure in chicken embryos by inhibiting endoplasmic reticulum stress and maintaining calcium homeostasis Ecotoxicology and Environmental Safety Cadmium Flavonoids Myocardium Development Chicken Embryos |
| title | Astilbin antagonizes developmental cardiotoxicity after cadmium exposure in chicken embryos by inhibiting endoplasmic reticulum stress and maintaining calcium homeostasis |
| title_full | Astilbin antagonizes developmental cardiotoxicity after cadmium exposure in chicken embryos by inhibiting endoplasmic reticulum stress and maintaining calcium homeostasis |
| title_fullStr | Astilbin antagonizes developmental cardiotoxicity after cadmium exposure in chicken embryos by inhibiting endoplasmic reticulum stress and maintaining calcium homeostasis |
| title_full_unstemmed | Astilbin antagonizes developmental cardiotoxicity after cadmium exposure in chicken embryos by inhibiting endoplasmic reticulum stress and maintaining calcium homeostasis |
| title_short | Astilbin antagonizes developmental cardiotoxicity after cadmium exposure in chicken embryos by inhibiting endoplasmic reticulum stress and maintaining calcium homeostasis |
| title_sort | astilbin antagonizes developmental cardiotoxicity after cadmium exposure in chicken embryos by inhibiting endoplasmic reticulum stress and maintaining calcium homeostasis |
| topic | Cadmium Flavonoids Myocardium Development Chicken Embryos |
| url | http://www.sciencedirect.com/science/article/pii/S0147651323013519 |
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