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Ferrous Oxide Nanoparticles Induced Abnormal Cardiac Development in Zebrafish Through Hypoxia and Ferroptosis

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Chemical Research in Chinese Universities Aims and scope

Abstract

Ferrous oxide nanoparticles(nFeO) have potential applications in biomedicine, industrial processes, and waste water treatment. However, the biocompatibility of nFeO remains uncertain. In this study, we synthesized rhombus-shaped nFeO and exposed them to zebrafish embryos to investigate the bio-safety of nFeO. Our results showed that exposure to nFeO led to pericardial edema, heart bleeding, and enlarged ventricles. Furthermore, the content of dissolved oxygen decreased. Fe2+ ions, which were released from the core of nFeO, were oxidized into Fe3+. This caused the overexpression of tfa and fpn genes, which carried Fe3+ into and out of the cell membrane, respectively. The overload of Fe3+ caused ferroptosis in zebrafish larvae, which was evidenced by the overexpression of the marker gene ptgs2 and the marker production malondialdehyde(MDA) of ferroptosis. However, neither the ferrostatin-1(Fer-1) inhibitor nor deferoxiamine(DFO) could completely rescue the toxicity caused by nFeO. We found that co-treatment of nFeO with CaO2, a dissolved oxygen donor, and Fer-1 or DFO could totally rescue pericardial edema and heart bleeding. Our results provide new knowledge that both hypoxia and ferroptosis play important roles in nFeO-induced zebrafish cardiac developmental toxicity, which is beneficial for the development and safe application of iron-based nanomaterials in the future.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (No.42177411), the Youth Innovation Fund Project of Xiamen, China (No.3502Z20206087), and the Guiding Project of Science and Technology in Medical and Health Field of Quanzhou City, China(No.2022N029S).

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  1. These authors contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Cellular Stress Biology, Xiang’an Hospital of Xiamen University, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, 361102, China

    Naying Zheng, Tingting Liao & Zhenghong Zuo

  2. Department of Microbiology and Immunology, Fujian Provincial Key Laboratory of Functional and Clinical Translational Medicine, Xiamen Key Laboratory of Respiratory Diseases, Xiamen Medical College, Xiamen, 361023, China

    Shuzhen Chen

  3. Chest Pain Center, Anxi County Hospital, Quanzhou, 362400, China

    Xintan Chen & Ruyu Zhan

  4. State Key Laboratory of Natural Medicines, Key Laboratory of Drug Quality Control and Pharmacovigilance, Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, 210009, China

    Yiyue Shi & Xiaolian Sun

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  1. Naying Zheng
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  2. Xintan Chen
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  7. Shuzhen Chen
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Correspondence to Shuzhen Chen or Zhenghong Zuo.

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Zheng, N., Chen, X., Zhan, R. et al. Ferrous Oxide Nanoparticles Induced Abnormal Cardiac Development in Zebrafish Through Hypoxia and Ferroptosis. Chem. Res. Chin. Univ. 39, 502–507 (2023). https://doi.org/10.1007/s40242-023-3055-8

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  • DOI: https://doi.org/10.1007/s40242-023-3055-8

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