Oxidative and Inflammatory Damage by Environmental Polyethylene Microplastics in Caco-2 Cells Is Prevented by Polyphenol-Rich Limoncella Apple Extract

Background: Humans are constantly exposed to environmental microplastic (MP) particles, which can be absorbed through the gut and exert adverse health effects. This study aimed to investigate the harmful effects of environmental polyethylene MPs (PE, 2.6 μm) on differentiated Caco-2 (D-Caco-2) intestinal epithelial cells and to assess the protective potential of Limoncella apple polyphenol extract (LAPE). Methods: D-Caco-2 cells were exposed to PE, LAPE, or their combination. Cell viability and lipid peroxidation were evaluated using MTT and TBARS assays, respectively. The organization of F-actin and alkaline phosphatase proteins was evaluated by immunofluorescence, whereas occludin and NF-κB were evaluated by Western blot analysis. Results: PE reduced D-Caco-2 viability and impaired cell differentiation by increasing lipid peroxidation. In addition, PE destructured F-actin organization and altered the expression of occludin, a tight-junction protein. Conclusions: Our findings show that PE increases oxidative stress, triggering epithelial–mesenchymal transition and dedifferentiation in Caco-2 cells. Interestingly, LAPE, owing to its antioxidant and anti-inflammatory properties, counteracted the harmful effects of PE, suggesting its potential as a nutraceutical strategy to prevent MP-induced damage in the gastrointestinal (GI) tract.