A Drosophila model of gestational antimony exposure uncovers growth and developmental disorders caused by disrupting oxidative stress homeostasis

• Published in: Free radical biology & medicine 2023-11, Vol.208, p.418-429
• Main Authors: Wang, Xiaoke, Zhou, Peiyao, Zhang, Ziyang, Huang, Qiuru, Chen, Xia, Ji, Li, Cheng, Xinmeng, Shi, Yi, Yu, Shali, Tang, Juan, Sun, Chi, Zhao, Xinyuan, Yu, Jun
• Format: Article
• Language: English
• Subjects: Antimony; Development; Drosophila; Oxidative stress; Toxicity
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2023.09.002

The toxic heavy metal antimony (Sb) is ubiquitous in our daily lives. Various models have shown that Sb induces neuronal and reproductive toxicity. However, little is known about the developmental toxicity of Sb exposure during gestation and the underlying mechanisms. To study its effects on growth and development, Drosophila stages from eggs to pupae were exposed to different Sb concentrations (0, 0.3, 0.6 and 1.2 mg/mL Sb); RNA sequencing was used to identify the underlying mechanism. The model revealed that prenatal Sb exposure significantly reduced larval body size and weight, the pupation and eclosion rates, and the number of flies at all stages. With 1.2 mg/mL Sb exposure in 3rd instar larvae, 484 genes were upregulated and 694 downregulated compared to controls. Biological analysis showed that the disrupted transcripts were related to the oxidative stress pathway, as verified by reactive oxygen species (ROS) scavenger N-acetylcysteine (NAC) and glutathione (GSH) intervention experiments. Sb exposure induced oxidative stress imbalance could be rectified by chelation and antioxidant effects of NAC/GSH. The Drosophila Schneider 2 (S2) model further demonstrated that NAC and GSH greatly ameliorated cell death induced by Sb exposure. In conclusion, gestational Sb exposure disrupted oxidative stress homeostasis, thereby impairing growth and development. [Display omitted] •A Drosophila model of gestational Sb exposure was performed to investigate effects on development.•Sb exposure reduced larval body size, larval weight, pupation and eclosion rates.•Sb exposure induced genotoxicity related with oxidative stress pathway.•Sb mediated oxidative stress imbalance was rectified by chelation and antioxidant effects of NAC/GSH.