College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China; College of Life Sciences, South China Agricultural University, Guangzhou 510642, China.
College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.
Pestic Biochem Physiol. 2024 May;201:105904. doi: 10.1016/j.pestbp.2024.105904. Epub 2024 Apr 10.
Arsenic (As) and polystyrene nanoplastics (PSNPs) co-exposure induced biotoxicity and ecological risks have attracted wide attention. However, the combined effects of As and PSNPs on the kidney and their underlying mechanisms of toxicities remain to be explored. Here, we investigated the effects of As and PSNPs co-exposure on structure and function in mice kidney, and further explored the possible mechanisms. In this study, we identified that co-exposure to As and PSNPs exhibited conspicuous renal structural damage and pathological changes, accompanied by renal tissue fibrosis (increased protein expression of Collagen I and α-SMA and deposition of collagen fibers), whereas alone exposure to As or PSNPs does not exhibit nephrotoxicity. Subsequently, our results further showed that combined action of As and PSNPs induced mitochondrial oxidative damage and impaired mitochondrial dynamic balance. Furthermore, co-treatment with As and PSNPs activated NCOA4-mediated ferritinophagy and ferroptosis in mice kidney and TCMK-1 cells, which was confirmed by the changes in the expression of ferritinophagy and ferroptosis related indicators (NCOA4, LC3, ATG5, ATG7, FTH1, FTL, GPX4, SLC7A11, FSP1, ACSL4 and PTGS2). Meaningfully, pretreatment with the mtROS-targeted scavenger Mito-TEMPO significantly attenuated As and PSNPs co-exposure induced mitochondrial damage, ferritinophagy and ferroptosis. In conclusion, these findings demonstrated that mtROS-dependent ferritinophagy and ferroptosis are important factors in As and PSNPs co-exposure induced kidney injury and fibrosis. This study provides a new insight into the study of combined toxicity of nanoplastics and heavy metal pollutants.
砷（As）和聚苯乙烯纳米塑料（PSNPs）共同暴露引起的生物毒性和生态风险引起了广泛关注。然而，As 和 PSNPs 共同暴露对肾脏的联合作用及其毒性的潜在机制仍有待探索。在这里，我们研究了 As 和 PSNPs 共同暴露对小鼠肾脏结构和功能的影响，并进一步探讨了可能的机制。在这项研究中，我们发现 As 和 PSNPs 共同暴露表现出明显的肾脏结构损伤和病理变化，伴有肾组织纤维化（胶原蛋白 I 和α-SMA 蛋白表达增加和胶原蛋白纤维沉积），而单独暴露于 As 或 PSNPs 则不会引起肾毒性。随后，我们的结果进一步表明，As 和 PSNPs 的联合作用诱导了线粒体氧化损伤并破坏了线粒体的动态平衡。此外，As 和 PSNPs 的共同处理激活了 NCOA4 介导的铁蛋白自噬和铁死亡，这在铁蛋白自噬和铁死亡相关指标（NCOA4、LC3、ATG5、ATG7、FTH1、FTL、GPX4、SLC7A11、FSP1、ACSL4 和 PTGS2）的表达变化中得到了证实。有意义的是，mtROS 靶向清除剂 Mito-TEMPO 的预处理显著减轻了 As 和 PSNPs 共同暴露引起的线粒体损伤、铁蛋白自噬和铁死亡。总之，这些发现表明，mtROS 依赖性铁蛋白自噬和铁死亡是 As 和 PSNPs 共同暴露引起肾脏损伤和纤维化的重要因素。本研究为纳米塑料和重金属污染物联合毒性的研究提供了新的视角。
