Deleterious effects of plastic component bisphenol a on mitochondrial function in human intestinal cells

Plastic compounds released into the environment can be accumulated in human tissues causing various health issues. It has been demonstrated that Bisphenol A (BPA), widely used in polycarbonate plastics and food packaging, can accumulate in gastrointestinal (GI) tract, inducing oxidative stress, metabolic dysfunction, and other cellular disturbances, including mitochondrial damage. However, the mechanisms by which BPA affects the GI function and affects mitochondrial function in the absorptive cells of the intestine, are still not completely understood. The aim of this study is to investigate whether BPA enters intact human intestinal cells and affects mitochondrial electron transport chain (ETC) function. High-resolution respirometry (O2k system, OROBOROS) and fluorometry were used to assess mitochondrial respiration and membrane potential (mt-MP) in Caco-2 cells under acute exposure to BPA. Cellular respiration was stimulated with complex I (C-I), II (C-II), IV (C-IV) and β-oxidation substrates in both intact and permeabilized Caco-2 cells. Morphological analysis of cells exposed to BPA was performed by electron microscopy. In intact cells, respiration rate decreased in presence of BPA, thus confirming the detrimental effects of BPA on ETC. In permeabilized cells, BPA caused a decrease of respiratory activity in presence of C-I and C-II substrates following a reduction of the ETC oxidative capacity and a depolarization of mt-MP. Morphological analysis suggested that BPA can be internalized by endocytosis. The reduced respiration rate in both intact and permeabilized cells indicates that BPA reaches mitochondria even without membrane permeabilization. BPA compromises both oxidative phosphorylation (OxPhos) and mt-MP, thus leading to an impairment of energy metabolism that could contribute to pathological alterations of the gastrointestinal function.