Hepatotoxic of polystyrene microplastics in aged mice: Focus on the role of gastrointestinal transformation and AMPK/FoxO pathway

Microplastic (MP) toxicity has attracted widespread attention, whereas before triggering hepatotoxicity, ingested MPs first undergo transportation and digestion processes in the gastrointestinal tract, possibly interacting with the gastrointestinal contents (GIC). More alarming is the need for more understanding of how this process may impact the liver health of aged animals. This study selected old mice. Firstly, we incubated polystyrene microplastics (PS-MPs, 1 μm) with GIC extract. The results of SEM/EDS indicated a structural alteration in PS-MPs. Additionally, impurities resembling corona, rich in heteroatoms (O, N, and S), were observed. This resulted in an enhanced aggregating phenomenon of MPs. We conducted a 10-day experiment exposing aged mice to four concentrations of PS-MPs, ranging from 1 × 103 to 1 × 1012 particles/L. Subsequent measurements of tissue pathology and body and organ weights were conducted, revealing alterations in liver structure. In the liver, 12 crucial metabolites were found by LC-MS technology, including purines, lipids, and amino acids. The AMPK/FoxO pathway was enriched, activated, and validated in western blotting results. We also comprehensively examined the innate immune system, inflammatory factors, and oxidative stress indicators. The results indicated decreased C3 levels, stable C4 levels, inflammatory factors (IL-6 and IL-8), and antioxidant enzymes were increased to varying degrees. PS-MPs also caused DNA oxidative damage. These toxic effects exhibited a specific dose dependence. Overall, after the formation of the gastrointestinal corona, PS-MPs subsequently impact various cellular processes, such as cycle arrest (p21), leading to hepatic and health crises in the elderly. The presence of gastrointestinal coronas also underscores the MPs' morphology and characteristics, which should be distinguished after ingestion.