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.

Are Persistent Organic Pollutants Linked to Lipid Abnormalities, Atherosclerosis and Cardiovascular Disease? A Review

“…Second, several experimental studies have shown that PCBs increased reactive oxygen species and oxidative stress. 48 51 52 53 Similar findings have also been reported by us in humans. 54 In that study, PCBs and OC pesticides were related to circulating levels of oxidized LDL and conjugated diens.…”

“…Exposure of human umbilical vein endothelial cells (HUVECs) to PCB-118 attenuated insulin-induced NO production and activity of endothelial NO synthase. 51 Furthermore, PCB104 exposure of ex vivo rat aortic attenuated acetylcholine-mediated vasodilation, an NO-dependent process. 55 Fourth, apoptosis of endothelial cells is one mechanism in atherosclerosis formation.…”

Endocrine-disrupting chemicals and risk of diabetes: an evidence-based review

“…β-blockers, thiazide diuretics and neuroleptic drugs). Several downstream effects of the agonistic/antagonistic actions on the receptors described above, such as mitochondrial dysfunction [ 38 ], inflammation [ 39 ], oxidative stress [ 40 ] and alterations in thyroid and cortisol pathways [ 41 ], comprise possible mediating pathways linking different EDCs to glucose disturbances.…”

Isorhapontigenin ameliorates cerebral ischemia/reperfusion injury via modulating Kinase Cε/Nrf2/HO‐1 signaling pathway

“…Oxidative stress is one of the critical pathological mechanisms of ischemic stroke (Jena et al., 2017 ). Excessive ROS are mainly derived from mitochondria with a functional disorder, causing peroxidative damage of nucleic acids, lipids and proteins, and impairing normal physiological functions (Yang, Can, et al., 2017 ). Excessive ROS production promotes pathological processes of neurodegenerative diseases (Zhao et al., 2015 ).…”