Abstract：
Polystyrene microplastic (PS-MPs) contamination has become a worldwide hotspot of concern, and its entry into organisms can cause oxidative stress resulting in multi-organ damage. The plasticizer di (2-ethylhexyl) phthalate (DEHP) is a common endocrine disruptor, these two environmental toxins often occur together, but their combined toxicity to the kidney and its mechanism of toxicity are unknown. Therefore, in this study, we established PS-MPS and/or DEHP-exposed mouse models. The results showed that alone exposure to both PS-MPs and DEHP caused inflammatory cell infiltration, cell membrane rupture, and content spillage in kidney tissues. There were also down-regulation of antioxidant enzyme levels, increased ROS content, activated of the NF-κB pathway, stimulated the levels of heat shock proteins (HSPs), pyroptosis, and inflammatory associated factors. Notably, the co-exposure group showed greater toxicity to kidney tissues, the cellular assay further validated these results. The introduction of the antioxidant n-acetylcysteine (NAC) and the NLRP3 inhibitor (MCC950) could mitigate the changes in the above measures. In summary, co-exposure of PS-MPs and DEHP induced oxidative stress that activated the NF-κB/NLRP3 pathway and aggravated kidney pyroptosis and inflammation, as well as that HSPs are also involved in this pathologic injury process. This study not only enriched the nephrotoxicity of plasticizers and microplastics, but also provided new insights into the toxicity mechanisms of multicomponent co-pollution in environmental.
摘要：
聚苯乙烯微塑料(PS-MPs)污染已成为全球关注的热点,并且其进入生物体会引起氧化应激，从而导致多器官损伤。增塑剂邻苯二甲酸二(2-乙基己基)酯(DEHP)是一种常见的内分泌干扰物,这两种环境毒素经常同时发生，但它们对肾脏的综合毒性及其毒性机制尚不清楚。因此,在这项研究中，我们建立了PS-MPS和/或DEHP暴露的小鼠模型。结果表明，单独暴露于PS-MPs和DEHP会引起炎症细胞浸润，细胞膜破裂,和内容物溢出到肾脏组织中。抗氧化酶水平也下调，ROS含量增加，NF-κB通路的激活，刺激热休克蛋白（HSPs）的水平，焦亡,和炎症相关因子。值得注意的是,共同暴露组对肾脏组织表现出更大的毒性，细胞试验进一步验证了这些结果.抗氧化剂N-乙酰半胱氨酸（NAC）和NLRP3抑制剂（MCC950）的引入可以减轻上述措施的变化。总之,PS-MPs和DEHP共同暴露诱导氧化应激，激活NF-κB/NLRP3通路，加重肾脏功能亢进和炎症反应，以及HSPs也参与了这一病理损伤过程。这项研究不仅丰富了增塑剂和微塑料的肾毒性，同时也为多组分共污染在环境中的毒性机制提供了新的见解。
