School of Animal Science and Technology, Henan University of Science and Technology, Luoyang 471003, China.
School of Animal Science and Technology, Henan University of Science and Technology, Luoyang 471003, China.
Aquat Toxicol. 2024 Oct;275:107078. doi: 10.1016/j.aquatox.2024.107078. Epub 2024 Sep 2.
In recent years, there is a great concern about the potential adverse effects of carbon nanotubes (CNTs) on the aquatic systems due to their increasingly extensive application. In this study, juvenile Cyprinus carpio were exposed to multi-walled CNTs (MWCNTs) at concentrations of 0, 0.25, and 2.5 mg L for 28 days. Then, oxidative stress indicators and metabolite profile of the livers were assessed. Results showed the significant increase of malondialdehyde (MDA) content and decrease of glutathione (GSH) activities in fish treated with 2.5 mg L MWCNTs. LC-MS untargeted metabolomics demonstrated that 406 and 274 metabolites in fish treated with 2.5 mg L MWCNTs were significantly up- and down-regulated, respectively. KEGG functional annotation analysis showed the disturbance of amino acid metabolism, lipid metabolism, and nucleotide metabolism. In addition, ferroptosis signaling pathway was detected. Therefore, iron content analysis and quantitative real-time RT-PCR assay were performed furtherly to validate the contribution of ferroptosis to MWCNTs-induced hepatotoxicity. The iron content increased significantly and the mRNA levels of ferroptosis-related genes including STEAP3, ACSL4, NCOA4, TFR1, NRF2, SLC3A2, SLC7A11, GPX4, and FPN1 were also obviously changed. Taken together, our study suggested that MWCNTs exposure-induced ferroptosis were associated with iron overload and lipid peroxidation via NRF2/SLC7A11/GSH/GPX4 axis. Our findings provide essential information to understand the mechanism of CNTs-induced hepatotoxicity in fish and explore potential biomarkers.
近年来，由于碳纳米管（CNTs）的应用越来越广泛，人们对其对水生系统可能产生的不良影响非常关注。在这项研究中，将幼鲤暴露于浓度为 0、0.25 和 2.5 mg/L 的多壁碳纳米管（MWCNTs）中 28 天。然后，评估了肝脏的氧化应激指标和代谢物谱。结果表明，用 2.5 mg/L MWCNTs 处理的鱼的丙二醛（MDA）含量显著增加，谷胱甘肽（GSH）活性降低。LC-MS 无靶向代谢组学表明，用 2.5 mg/L MWCNTs 处理的鱼中有 406 种和 274 种代谢物分别显著上调和下调。KEGG 功能注释分析表明，氨基酸代谢、脂质代谢和核苷酸代谢受到干扰。此外，还检测到铁死亡信号通路。因此，进一步进行了铁含量分析和定量实时 RT-PCR 测定，以验证铁死亡对 MWCNTs 诱导的肝毒性的贡献。铁含量显著增加，铁死亡相关基因包括 STEAP3、ACSL4、NCOA4、TFR1、NRF2、SLC3A2、SLC7A11、GPX4 和 FPN1 的 mRNA 水平也明显改变。总之，我们的研究表明，MWCNTs 暴露诱导的铁死亡与铁过载和脂质过氧化有关，通过 NRF2/SLC7A11/GSH/GPX4 轴。我们的研究结果为理解鱼类 CNTs 诱导的肝毒性机制和探索潜在生物标志物提供了重要信息。
