Exposure to Polyethylene Terephthalate Microplastic Induces Mouse Liver Fibrosis Through Oxidative Stress and p38 MAPK/p65 NF-κB Signaling Pathway.

Abstract

Microplastic (MP) pollution has garnered attention due to its potential impact on living organisms. Among these, polyethylene terephthalate microplastics (PET-MPs) are frequently detected in both environmental samples and human tissues. Despite this, the effects of PET-MPs on liver damage and fibrosis in mammals remain insufficiently understood. This study demonstrated that oral exposure to PET-MPs at doses of 1 mg/day (with a diameter of 1 μm) over 42 days resulted in inhibited weight gain and altered organ coefficients in male mice, suggesting possible liver damage. Using HE and Masson staining revealed pathological changes in the livers of exposed mice, such as hepatocyte swelling, inflammatory cell infiltration, and collagen deposition. Liver function tests confirmed elevated serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Further, the elevated levels of oxidative stress markers, along with the enhanced expression of proteins related to the p38 MAPK/p65 NF-κB signaling pathway as revealed by western blot analysis, both of which are strongly associated with liver damage and fibrosis. To further elucidate these mechanisms, experiments involving N-acetylcysteine (NAC) to counteract oxidative stress and SB203580 to inhibit p38 MAPK activation demonstrated that both interventions effectively mitigated liver fibrosis. Exposure to PET-MPs may trigger liver injury and fibrosis in mice. During this process, oxidative stress and the p38 MAPK/p65 NF-κB signaling pathway may play significant mediating roles.