Abstract

There is a paucity of in vivo assays to investigate the potential deleterious effects of plastic-laden compounds in the gastrointestinal tract of mammals, compared to in vitro testing and ecotoxicity assays in marine organisms. This work aims to fill this gap through a comprehensive evaluation of the acute toxicokinetics and bioavailability of bisphenol A (BPA)-adsorbed medium-density polyethylene (PE) microplastics (MPs) (ca. 3000 mu g BPA/g), with a mean particle size of 136 mu m, which were administered via oral gavage at a mere 0.67 mg BPA/kg body weight for 24 h using a murine model. The determination of plasma BPA-glucuronide revealed that BPA associated with MPs (PE-BPA) is bioavailable to a similar extent to that of freely dissolved BPA, with Area Under the Curves (AUC) values of 1249 f 182 and 928 f 276 mu g h & sdot;L- 1 for the 0 -> 6 h interval (AUC0 -> 6h), and 3586 f 526 and 2325 f 634 mu g h & sdot;L- 1 for the 0 -> 24 h interval (AUC0 -> 24h), corresponding to PE-BPA and free BPA, respectively. Several biomarker assays of the small intestine and liver, and the investigation of the gut barrier function were conducted to elucidate the potential deleterious effects of PE-BPA as compared to BPA and PE alone. Acute exposure to PE-BPA increased the expression of the detoxification biomarkers multidrug resistance protein 1 (MDR1) and UDP-glucuronosyltransferase 2b1 (UGT2b1) in the jejunum, particularly when PE and BPA occurred together, likely due to the extended intestinal residence time of the BPA-laden MPs. Oxidative stress markers, such as superoxide dismutase activity, and inflammatory responses, evaluated by myeloperoxidase activity, were also elevated in the PE-BPA group, suggesting a defensive response but without evidence of oxidative damage as determined by the malondialdehyde levels. In conclusion, the findings suggest that BPA associated with MPs exhibits similar bioavailability than that of freely dissolved BPA, with the subsequent activation of detoxification pathways and inflammatory responses.