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Co-Exposure to Polystyrene Microplastics and Bisphenol A Contributes to the Formation of Liver Fibrosis in Mice
Bonan Xiao1,2,3, Wanghao Yang1,2,3, Hao Dong1,2,3
1Northwest A&F University, Yangling, Shaanxi 712100, China.
Abstract:
The food safety risks posed by exposure to polystyrene microplastics (PS-MPs) and bisphenol A (BPA) have become an issue worldwide. However, the toxic effects of PS-MPs and BPA coexposure on the mammalian liver remain elusive. In this study, we found that PS-MPs and BPA coexposure have synergistic toxic effects on AML12 cells and the mouse liver. Histopathological staining revealed excessive accumulation of the extracellular matrix in the coexposure liver. Co-exposure to PS-MPs and BPA downregulated Bmal1 and E-cad both in vitro and in vivo. Additionally, Bmal1 AML12 cells and liver-specific Bmal1 mice exhibited significantly reduced E-cad levels, with no significant reduction under PS-MPs and BPA coexposure. Notably, overexpression of BMAL1 and CLOCK significantly enhanced luciferase activity driven by the E-cad gene intron region (containing an E-box cis-element). These results demonstrated that coexposure to PS-MPs and BPA contributed to the development of liver fibrosis by inhibiting the BMAL1/E-cad signaling pathway.
Insights
Polystyrene microplastics (PS-MPs) and bisphenol A (BPA) exposure synergistically harm the liver by inhibiting the BMAL1/E-cad pathway, leading to fibrosis. This research clarifies the toxic effects of these common contaminants.
Area of Science:
- Environmental Health
- Toxicology
- Molecular Biology
Background:
- Food safety concerns regarding polystyrene microplastics (PS-MPs) and bisphenol A (BPA) are globally significant.
- The combined toxicological impact of PS-MPs and BPA on mammalian liver function is not well understood.
Purpose of the Study:
- To investigate the synergistic toxic effects of PS-MPs and BPA coexposure on liver cells and mouse livers.
- To elucidate the molecular mechanisms underlying PS-MP and BPA-induced liver damage.
Main Methods:
- Utilized AML12 cells and mouse models for in vitro and in vivo studies.
- Performed histopathological staining to assess liver tissue changes.
- Quantified the expression levels of Bmal1 and E-cad genes.
- Conducted luciferase reporter assays to examine gene regulation.
Main Results:
- Coexposure to PS-MPs and BPA demonstrated synergistic toxicity in AML12 cells and mouse livers.
- Histopathology revealed excessive extracellular matrix accumulation, indicative of fibrosis.
- Bmal1 and E-cad gene expression were downregulated following coexposure.
- BMAL1 and CLOCK overexpression enhanced E-cad gene activity, suggesting a regulatory role.
Conclusions:
- Coexposure to PS-MPs and BPA promotes liver fibrosis by suppressing the BMAL1/E-cad signaling pathway.
- The study identifies a novel mechanism of toxicity for these prevalent environmental contaminants.
- Findings highlight the critical need for assessing combined exposure risks in food safety.
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