Aged fragmented-polypropylene microplastics induced ageing statues-dependent bioenergetic imbalance and reductive stress: In vivo and liver organoids-based in vitro study

• DOI: 10.1016/j.envint.2024.108949
• Publication Date: 2024-08-15T22:31:49Z
• Authors: Wei Cheng; Hange Chen; Yue Zhou; Yifei You; Dong Lei; Yan Li; Yan Feng; Yan Wang
• Keywords: Bioenergetics

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