2,3',4,4',5-Pentachlorobiphenyl impairs insulin-induced NO production partly through excessive ROS production in endothelial cells.

ABSTRACT

Polychlorinated biphenyls (PCBs) have been reported to be associated with increased risk to hypertension, atherosclerosis, cardiovascular disease, etc. 2,3',4,4',5-Pentachlorobiphenyl, known as PCB-118, is a member of coplanar PCBs which renders their structure similar to polychlorinated dibenzo-p-dioxins (PCDDs) and has dioxin-like activity. In our current study, we investigated the effect of PCB-118 exposure on nitric oxide (NO) production and the underlying mechanisms in vitro. Exposure of PCB-118 impaired insulin-induced NO production and endothelial nitric oxide synthase (eNOS) activity in human umbilical vein endothelial cells (HUVECs) with no significant effect on cell viability. Furthermore, PCB-118 treatment induced oxidative stress. In addition, scavenging of reactive oxygen species (ROS) by 10 µM N-acetyl-l-cysteine (NAC) partly rescued impaired insulin-induced eNOS activities and NO productions induced by PCB-118 in HUVECs. Taken together, these results indicate that PCB-118 mediates lower eNOS activity and impairs insulin-induced NO production partly through excessive ROS production in endothelial cells.