Exploring oxidative stress and endothelial dysfunction as a mechanism linking bisphenol S exposure to vascular disease in human umbilical vein endothelial cells and a mouse model of postnatal exposure
Background: Structural analogues used to replace bisphenol A (BPA) since the introduction of new regulatory restrictions are considered emerging environmental toxicants and remain understudied with respect to their biological actions and health effects. Studies reveal a link between BPA exposure and...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-12-01
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| Series: | Environment International |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S016041202200530X |
| _version_ | 1811206840711643136 |
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| author | Sarah Easson Radha Dutt Singh Liam Connors Taylor Scheidl Larissa Baker Anshul Jadli Hai-Lei Zhu Jennifer Thompson |
| author_facet | Sarah Easson Radha Dutt Singh Liam Connors Taylor Scheidl Larissa Baker Anshul Jadli Hai-Lei Zhu Jennifer Thompson |
| author_sort | Sarah Easson |
| collection | DOAJ |
| description | Background: Structural analogues used to replace bisphenol A (BPA) since the introduction of new regulatory restrictions are considered emerging environmental toxicants and remain understudied with respect to their biological actions and health effects. Studies reveal a link between BPA exposure and vascular disease in human populations, whereas the vascular effects of BPA substitutes remain largely unknown. Objectives: To determine the effect of BPS, a commonly used BPA substitute, on redox balance, nitric oxide (NO) availability and microvascular NO-dependent dilation. Methods: In human umbilical vein endothelial cells (HUVEC), production of reactive oxygen species (ROS) and NO after exposure to BPS was measured using fluorescent probes for DCFDA and DAF-FM diacetate, respectively. The contribution of endothelial NO synthase (eNOS) uncoupling to ROS generation was determined by measuring ROS in the presence or absence of an eNOS inhibitor (L-NAME) or eNOS co-factor, BH4, while the contribution of mitochondria-derived ROS was determined by treating cells with mitochondria-specific antioxidants prior to BPS exposure. Bioenergetic profiles were assessed using Seahorse extracellular flux analysis and mitochondria membrane polarization was measured with TMRE and JC-1 assays. In a mouse model of low dose BPS exposure, NO-mediated endothelial function was assessed in pressurized microvessels by inducing endothelium-dependent dilation in the presence or absence of L-NAME. Results: BPS exposure (≥25 nM) reduced NO and increased ROS production in HUVEC, the latter corrected by treating cells with L-NAME or BH4. BPS exposure led to a loss of mitochondria membrane potential but had no impact on bioenergetic parameters except for a decrease in the spare respiratory capacity. Treatment of HUVEC with mitochondria-specific antioxidants abolished the effect of BPS on NO and ROS. NO-mediated vasodilation was impaired in male mice exposed to BPS. Discussion: Exposure to BPS may promote cardiovascular disease by perturbing NO-mediated vascular homeostasis through the induction of oxidative stress. |
| first_indexed | 2024-04-12T03:53:37Z |
| format | Article |
| id | doaj.art-3279097c40be47c6bd3a78de430b519f |
| institution | Directory Open Access Journal |
| issn | 0160-4120 |
| language | English |
| last_indexed | 2024-04-12T03:53:37Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Environment International |
| spelling | doaj.art-3279097c40be47c6bd3a78de430b519f2022-12-22T03:48:53ZengElsevierEnvironment International0160-41202022-12-01170107603Exploring oxidative stress and endothelial dysfunction as a mechanism linking bisphenol S exposure to vascular disease in human umbilical vein endothelial cells and a mouse model of postnatal exposureSarah Easson0Radha Dutt Singh1Liam Connors2Taylor Scheidl3Larissa Baker4Anshul Jadli5Hai-Lei Zhu6Jennifer Thompson7Department of Physiology and Pharmacology, University of Calgary, 3330 Hospital Dr. NW, Calgary, Alberta T2N 1N4, CanadaDepartment of Physiology and Pharmacology, University of Calgary, 3330 Hospital Dr. NW, Calgary, Alberta T2N 1N4, Canada; Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Canada; Alberta Children’s Hospital Research Institute, Cumming School of Medicine, University of Calgary, CanadaDepartment of Physiology and Pharmacology, University of Calgary, 3330 Hospital Dr. NW, Calgary, Alberta T2N 1N4, Canada; Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, CanadaDepartment of Physiology and Pharmacology, University of Calgary, 3330 Hospital Dr. NW, Calgary, Alberta T2N 1N4, Canada; Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Canada; Alberta Children’s Hospital Research Institute, Cumming School of Medicine, University of Calgary, CanadaDepartment of Physiology and Pharmacology, University of Calgary, 3330 Hospital Dr. NW, Calgary, Alberta T2N 1N4, CanadaDepartment of Physiology and Pharmacology, University of Calgary, 3330 Hospital Dr. NW, Calgary, Alberta T2N 1N4, Canada; Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, CanadaDepartment of Physiology and Pharmacology, University of Calgary, 3330 Hospital Dr. NW, Calgary, Alberta T2N 1N4, CanadaDepartment of Physiology and Pharmacology, University of Calgary, 3330 Hospital Dr. NW, Calgary, Alberta T2N 1N4, Canada; Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Canada; Alberta Children’s Hospital Research Institute, Cumming School of Medicine, University of Calgary, Canada; Corresponding author at: University of Calgary, Heritage Medical Research Building rm. 78, 3330 Hospital Dr. NW, Calgary, Alberta T2N 4N1, Canada.Background: Structural analogues used to replace bisphenol A (BPA) since the introduction of new regulatory restrictions are considered emerging environmental toxicants and remain understudied with respect to their biological actions and health effects. Studies reveal a link between BPA exposure and vascular disease in human populations, whereas the vascular effects of BPA substitutes remain largely unknown. Objectives: To determine the effect of BPS, a commonly used BPA substitute, on redox balance, nitric oxide (NO) availability and microvascular NO-dependent dilation. Methods: In human umbilical vein endothelial cells (HUVEC), production of reactive oxygen species (ROS) and NO after exposure to BPS was measured using fluorescent probes for DCFDA and DAF-FM diacetate, respectively. The contribution of endothelial NO synthase (eNOS) uncoupling to ROS generation was determined by measuring ROS in the presence or absence of an eNOS inhibitor (L-NAME) or eNOS co-factor, BH4, while the contribution of mitochondria-derived ROS was determined by treating cells with mitochondria-specific antioxidants prior to BPS exposure. Bioenergetic profiles were assessed using Seahorse extracellular flux analysis and mitochondria membrane polarization was measured with TMRE and JC-1 assays. In a mouse model of low dose BPS exposure, NO-mediated endothelial function was assessed in pressurized microvessels by inducing endothelium-dependent dilation in the presence or absence of L-NAME. Results: BPS exposure (≥25 nM) reduced NO and increased ROS production in HUVEC, the latter corrected by treating cells with L-NAME or BH4. BPS exposure led to a loss of mitochondria membrane potential but had no impact on bioenergetic parameters except for a decrease in the spare respiratory capacity. Treatment of HUVEC with mitochondria-specific antioxidants abolished the effect of BPS on NO and ROS. NO-mediated vasodilation was impaired in male mice exposed to BPS. Discussion: Exposure to BPS may promote cardiovascular disease by perturbing NO-mediated vascular homeostasis through the induction of oxidative stress.http://www.sciencedirect.com/science/article/pii/S016041202200530XBisphenolEndothelial functionOxidative stressMitochondria |
| spellingShingle | Sarah Easson Radha Dutt Singh Liam Connors Taylor Scheidl Larissa Baker Anshul Jadli Hai-Lei Zhu Jennifer Thompson Exploring oxidative stress and endothelial dysfunction as a mechanism linking bisphenol S exposure to vascular disease in human umbilical vein endothelial cells and a mouse model of postnatal exposure Environment International Bisphenol Endothelial function Oxidative stress Mitochondria |
| title | Exploring oxidative stress and endothelial dysfunction as a mechanism linking bisphenol S exposure to vascular disease in human umbilical vein endothelial cells and a mouse model of postnatal exposure |
| title_full | Exploring oxidative stress and endothelial dysfunction as a mechanism linking bisphenol S exposure to vascular disease in human umbilical vein endothelial cells and a mouse model of postnatal exposure |
| title_fullStr | Exploring oxidative stress and endothelial dysfunction as a mechanism linking bisphenol S exposure to vascular disease in human umbilical vein endothelial cells and a mouse model of postnatal exposure |
| title_full_unstemmed | Exploring oxidative stress and endothelial dysfunction as a mechanism linking bisphenol S exposure to vascular disease in human umbilical vein endothelial cells and a mouse model of postnatal exposure |
| title_short | Exploring oxidative stress and endothelial dysfunction as a mechanism linking bisphenol S exposure to vascular disease in human umbilical vein endothelial cells and a mouse model of postnatal exposure |
| title_sort | exploring oxidative stress and endothelial dysfunction as a mechanism linking bisphenol s exposure to vascular disease in human umbilical vein endothelial cells and a mouse model of postnatal exposure |
| topic | Bisphenol Endothelial function Oxidative stress Mitochondria |
| url | http://www.sciencedirect.com/science/article/pii/S016041202200530X |
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