Oral Administration of Polyethylene Microplastics Induces BPA-Associated Antioxidant Activation and Synaptic-Related...

Background/Objectives: The pervasive presence of microplastics (MPs) and plastic-associated chemicals has raised concerns regarding their potential effects on the central nervous system. Polyethylene (PE), widely used in food-contact materials, can carry bisphenol A (BPA), an endocrine disruptor with oxidative and neuroactive properties. Although both MPs and BPA can cross biological barriers, their acute effects on the prefrontal cortex (PFC) remain poorly understood. The aim of the study was to evaluate the acute impact of orally administered free BPA, free MPs, and BPA adsorbed onto PE MPs (PE-BPA) on oxidative stress, inflammation, and gene expression in the PFC of Wistar rats. Animals received a single dose of BPA, PE-BPA, PE alone, or vehicle. Methods: Biochemical and transcriptional analyses were performed to evaluate the antioxidant and inflammatory responses as well as the potential changes in synaptic-related gene expression. Results: BPA-containing treatments produced selective early molecular responses. Catalase (CAT) and glutathione S-transferase (GST) activities were significantly increased in the PE-BPA group, with GST being also elevated in the BPA-alone group, whereas superoxide dismutase (SOD), myeloperoxidase (MPO), and malondialdehyde (MDA) levels did not significantly change. Transcriptional analyses revealed upregulation of the antioxidant genes Nrf2 and CAT in the PE-BPA group. Co-exposure to BPA and MPs also altered synaptic markers, including decreased brain-derived neurotrophic factor (BDNF) and Sert along with increased Nr2A expression, while inflammatory gene expression remained unaffected. Conclusions: These findings indicate that acute co-exposure to BPA and PE microplastics elicits early antioxidant activation and selective synaptic-related transcriptional changes in the PFC, suggesting that MPs may modulate BPA-associated molecular responses in the brain.