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

doi:10.1007/s40242-023-3055-8

高等学校化学研究 ›› 2023, Vol. 39 ›› Issue (3): 502-507.doi: 10.1007/s40242-023-3055-8

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

Naying Zheng¹, Xintan Chen³, Ruyu Zhan³, Tingting Liao¹, Yiyue Shi⁴, Xiaolian Sun⁴, Shuzhen Chen², Zhenghong Zuo¹

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

收稿日期:2023-02-28 发布日期:2023-05-25
通讯作者: Shuzhen Chen, Zhenghong Zuo E-mail:cszlotus@126.com;zuozhenghong@xmu.edu.cn
基金资助:
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).

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

ZHENG Naying, CHEN Xintan, ZHAN Ruyu, LIAO Tingting, SHI Yiyue, SUN Xiaolian, CHEN Shuzhen, ZUO Zhenghong

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

Received:2023-02-28 Published:2023-05-25
Contact: Shuzhen Chen, Zhenghong Zuo E-mail:cszlotus@126.com;zuozhenghong@xmu.edu.cn
Supported by:
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).

摘要/Abstract

摘要： 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.

关键词: Nanoparticle, Biocompatibility, Heart, Zebrafish, Iron

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.

Key words: Nanoparticle, Biocompatibility, Heart, Zebrafish, Iron

Naying Zheng, Xintan Chen, Ruyu Zhan, Tingting Liao, Yiyue Shi, Xiaolian Sun, Shuzhen Chen, Zhenghong Zuo. Ferrous Oxide Nanoparticles Induced Abnormal Cardiac Development in Zebrafish Through Hypoxia and Ferroptosis[J]. 高等学校化学研究, 2023, 39(3): 502-507.

ZHENG Naying, CHEN Xintan, ZHAN Ruyu, LIAO Tingting, SHI Yiyue, SUN Xiaolian, CHEN Shuzhen, ZUO Zhenghong. Ferrous Oxide Nanoparticles Induced Abnormal Cardiac Development in Zebrafish Through Hypoxia and Ferroptosis[J]. Chemical Research in Chinese Universities, 2023, 39(3): 502-507.

参考文献

[1] Fernandes N., Rodrigues C. F., Moreira A. F., Correia I. J., Biomater. Sci., 2020, 8, 2990
[2] Miao Y., Chen Y., Xue F., Liu K., Zhu B., Gao J., Yin J., Zhang C., Li G., EBioMedicine, 2022, 76, 103847
[3] Adegbeye M. J., Elghandour M. M. M. Y., Barbabosa-Pliego A., Monroy J. C., Mellado M., Ravi Kanth Reddy P., Salem A. Z. M., J. Equine. Vet. Sci., 2019, 78, 29
[4] Lian L., Lv J., Wang X., Lou D., J. Chromatogr. A, 2018, 1534, 1
[5] Nezamzadeh-Ejhieh A., Shirzadi A., Chemosphere, 2014, 107, 136
[6] Lei C., Sun Y., Tsang D. C. W., Lin, D., Environ. Pollut., 2018, 232, 10
[7] Couto D., Freitas M., Vilas-Boas V., Dias I., Porto G., Lopez-Quintela M. A., Rivas J., Freitas P., Carvalho F., Fernandes E., Toxicol. Lett., 2014, 225, 57
[8] Sheykhbaglou R., Sedghi M., Fathi-Achachlouie B., An. Acad. Bras. Cienc., 2018, 90, 485
[9] Al-Rawi M., Al-Mudallal N., Taha A. A., Arch Razi Inst., 2021, 76, 795
[10] Gore A. V., Pillay L. M., Venero Galanternik M., Weinstein B. M., Wiley Interdiscip Rev. Dev. Biol., 2018, 7, e312
[11] Busse B., Galloway J. L., Gray R. S., Harris M. P., Kwon R. Y., J. Orthop. Res., 2020, 38, 925
[12] Horzmann K. A., Freeman J. L., Toxicol Sci., 2018, 163, 5
[13] MacRae C. A., Peterson R. T., Nat. Rev. Drug Discov., 2015, 14, 721
[14] Bambino K., Chu J., Curr. Top Dev. Biol., 2017, 124, 331
[15] Lebedeva L., Zhumabayeva B., Gebauer T., Kisselev I., Aitasheva Z., Zebrafish, 2020, 17, 359
[16] Zhou Z., Pope J. R., Johnson R. L., Jamieson W. D., Worthy H. L., Kailasam S., Ahmed R. D., Taban I., Auhim H. S., Watkins D. W., Rizkallah P. J., Castell O. K., Jones D. D., Angew. Chem. Int. Ed. Engl., 2017, 56, 6492
[17] Zheng N., Sun X., Shi Y., Chen L., Wang L., Cai H., Han C., Liao T., Yang C., Zuo Z., He C., Sci. Total Environ., 2022, 158715
[18] Lin S., Zhao Y., Ji Z., Ear J., Chang C. H., Zhang H., Low-Kam C., Yamada K., Meng H., Wang X., Liu R., Pokhrel S., Madler L., Damoiseaux R., Xia T., Godwin H. A., Lin S., Nel A. E., Small, 2013, 9(9/10), 1776
[19] Fang X., Wang H., Han D., Xie E., Yang X., Wei J., Gu S., Gao F., Zhu N., Yin X., Cheng Q., Zhang P., Dai W., Chen J., Yang F., Yang H. T., Linkermann A., Gu W., Min J., Wang F., Proc. Natl. Acad. Sci. USA, 2019, 116, 2672
[20] Yalcin H. C., Amindari A., Butcher J. T., Althani A., Yacoub M., Dev. Dyn., 2017, 246, 868
[21] Meng Y., Zhong K., Xiao J., Huang Y., Wei Y., Tang L., Chen S., Wu J., Ma J., Cao Z., Liao X., Lu H., Chemosphere, 2020, 255, 126889
[22] Li K., Wu J. Q., Jiang L. L., Shen L. Z., Li J. Y., He Z. H., Wei P., Lv Z., He M. F., Chemosphere, 2017, 171, 40
[23] Battaglia A. M., Chirillo R., Aversa I., Sacco A., Costanzo F., Biamonte F., Cells, 2020, 9, 6
[24] Li J., Cao F., Yin H. L., Huang Z. J., Lin Z. T., Mao N., Sun B., Wang G., Cell Death Dis., 2020, 11, 88
[25] Gao M., Monian P., Quadri N., Ramasamy R., Jiang X., Mol. Cell, 2015, 59, 298
[26] Park E., Chung S. W., Cell Death Dis., 2019, 10, 822
[27] Li Y., Zeng X., Lu D., Yin M., Shan M., Gao Y., Hum. Reprod., 2021, 36, 951
[28] Ma R., Fang L., Chen L., Wang X., Jiang J., Gao L., Theranostics, 2022, 12, 2266
[29] Gong Y., Wang N., Liu N., Dong H., DNA Cell Biol., 2019, 38, 725
[30] Zhang Z., Guo M., Li Y., Shen M., Kong D., Shao J., Ding H., Tan S., Chen A., Zhang F., Zheng S., Autophagy, 2020, 16, 1482
[31] Liu P., Feng Y., Li H., Chen X., Wang G., Xu S., Li Y., Zhao L., Cell Mol. Biol. Lett., 2020, 25, 10
[32] Chen C., Chen J., Wang Y., Liu Z., Wu Y., J. Biol. Chem., 2021, 296, 100187
[33] Small C. D., El-Khoury M., Deslongchamps G., Benfey T. J., Crawford B. D., J. Dev. Biol., 2020, 8, 1
[34] Fuhrmann D. C., Mondorf A., Beifuss J., Jung M., Brune B., Redox Biol., 2020, 36, 101670
[35] Lee C., Kim J. Y., Lee W. I., Nelson K. L., Yoon J., Sedlak D. L., Environ. Sci. Technol., 2008, 42, 4927
[36] Mandic M., Best C., Perry S. F., Proc. Biol. Sci., 2020, 287, 20200798
[37] Baba Y., Higa J. K., Shimada B. K., Horiuchi K. M., Suhara T., Kobayashi M., Woo J. D., Aoyagi H., Marh K. S., Kitaoka H., Matsui T., Am. J. Physiol. Heart Circ. Physiol., 2018, 314, H659

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

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

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