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

doi:10.1007/s40242-023-3055-8

Abstract

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

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.

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