Bisphenol S induced endothelial dysfunction via mitochondrial pathway in the vascular endothelial cells, and...

As a replacement of bisphenol A, bisphenol S (BPS) is commonly used in the wrappers and food containers of daily life. Epidemiological studies demonstrate a close link between BPS exposure and vascular diseases, where the biological activities of BPS remain scarcely known. Herein, the effects of BPS on endothelial function as well as the underlying mechanism were investigated in human umbilical vein endothelial cells (HUVECs) and mouse arteries. It was found that exposure of BPS dose-dependently induced endothelial dysfunction (i.e., decline of nitric oxide (NO) formation) in HUVECs, accompanied by the increase of reactive oxygen species (ROS) production and loss of mitochondria membrane potential. Mitochondria-specific antioxidant (Mito-Tempol) or superoxide scavenger (tiron) abolished the harmful effects of BPS, while superoxide dismutase (SOD)-specific siRNA exhibited negative influence, suggesting that mitochondrial ROS was responsible for BPS-induced endothelial dysfunction and SOD was a sensitive target of BPS. Consistently, plasma NO formation and endothelium-dependent vasodilation was significantly impaired in mice exposed to dietary BPS. In addition, the binding of bovine serum albumin (BSA, the most abundant protein in blood) to BPS considerably alleviated ROS formation and endothelial dysfunction in HUVECs. BPS primarily interacted with Sudlow site I of albumin to generate BSA-BPS complex through static mechanism, in which the hydrogen bonds and electrostatic forces played important roles. Altogether, dietary exposure to emerging BPS would disrupt vascular homeostasis via the induction of mitochondrial ROS formation and consequent endothelial dysfunction, highlighting the detoxification impact of albumin protein on the hazardous effects of environmental pollutants.