Ageing is a nature process of microplastics that occurrs daily, and human beings are inevitably exposed to aged microplastics. However, a systematic understanding of ageing status and its toxic effect is currently still lacking. In this study, plastic cup lids-originated polypropylene (PP) microplastics were UV-photoaged until the carbonyl index (CI), a canonical indicator for plastic ageing, achieved 0.08, 0.17, 0.22 and 0.28. The adverse hepatic effect of these aged PPs (aPPs) was evaluated in Balb/c mice (75 ng/mL water, about 200 particles/day) and human-originated liver organoids (LOs, 50 particles/mL, ranged from 5.94 to 13.15 ng/mL) at low-dose equivalent to human exposure level. Low-dose of aged PP could induce hepatic reductive stress both in vitro and in vivo, by elevating the NADH/NAD+ratio in a CI-dependent manner, together with hepatoxicity (indicated by increased AST secretion and cytotoxicity), and disrupted the genes encoding the nutrients transporters and NADH subunits accompanied by the restricted ATP supply, declined mitochondrial membrane potential and mitochondrial complexI/IV activities, without significant increase in MDA levels in the liver. These changes in the liver disrupted systematic metabolism, representing a circulatory panel of increases in the lactate, triglyceride, Fgf21 levels, and decreases in the pyruvate level, linked the reductive stress to the declined body weight gain but elevated hepatic NADH contents following aPPs exposure. Additionally, assessing by the LOs, it was found that digestion drastically accelerated the ageing of aPPs and worsen the energy supply upon mitochondria, representing a “scattergun effect” induced by the formation of micro- and nano-plastics mixture toward NADH/NAD+imbalance.

中文翻译：

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老化的聚丙烯微塑料碎片诱导衰老状态依赖性生物能量失衡和还原应激：基于体内和肝脏类器官的体外研究


老化是微塑料每天都会发生的自然过程，人类不可避免地会接触老化的微塑料。然而，目前仍然缺乏对衰老状况及其毒性作用的系统了解。在这项研究中，对源自塑料杯盖的聚丙烯 (PP) 微塑料进行紫外线光老化，直到羰基指数 (CI)（塑料老化的标准指标）达到 0.08、0.17、0.22 和 0.28。在 Balb/c 小鼠（75 ng/mL 水，约 200 个颗粒/天）和人源性肝脏类器官（LO，50 个颗粒/mL，范围为 5.94 至 13.15）中评估了这些老化 PP (aPP) 的不良肝脏影响。 ng/mL），低剂量相当于人体暴露水平。低剂量的老化 PP 可通过 CI 依赖性方式提高 NADH/NAD+ 比率，在体外和体内诱导肝脏还原应激，并产生肝毒性（表现为 AST 分泌增加和细胞毒性），并破坏基因编码营养物质转运蛋白和 NADH 亚基，伴随着 ATP 供应受限、线粒体膜电位和线粒体复合物 I/IV 活性下降，但肝脏中 MDA 水平没有显着增加。肝脏中的这些变化扰乱了系统代谢，代表了循环系统中乳酸、甘油三酯、Fgf21水平的增加和丙酮酸水平的降低，将还原应激与aPP暴露后体重增加下降但肝脏NADH含量升高联系起来。此外，LOs的评估发现，消化极大地加速了aPP的老化，并恶化了线粒体的能量供应，代表了微纳米塑料混合物的形成导致NADH/NAD+失衡的“散射枪效应” 。