title: Arsenic and fluoride induce apoptosis, inflammation and oxidative stress in cultured human umbilical vein endothelial cells.
abstract: Excessive amount of inorganic arsenic (iAs) and fluoride (F) coexist in drinking water in many regions, which is associated with high risk of vascular diseases. However, the underlying mechanisms are not well studied. The present study was to evaluate the effects of iAs and F individual or combined exposure on endothelial activation and apoptosis in vitro. Primary human umbilical vein endothelial cells (HUVECs) were exposed to 5 μM As2O3and/or 1 mM NaF. Changes in endothelial cell apoptosis, inflammation, oxidative stress and nitric oxide (NO) production were analyzed. The results showed that iAs and/or F induced significant increase in endothelial cell apoptosis and inflammation as indicated by the increase of mRNA and protein expression of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and pentraxin 3. Furthermore, iAs and/or F exposure induced intracellular reactive oxygen species and malondialdehyde generation. Results showed iAs and/or F exposure increased the activity of NADPH oxidase (NOX) and up-regulated the mRNA expression of NOX subunits p22phox. The results indicated that activation of NOX was related to oxidative stress induced by iAs and/or F. Also, iAs and/or F reduced NO production in HUVECs. The up-regulation of inflammation genes expression and oxidative stress in iAs and F co-exposed ECs were less pronounced as compared to single F-exposed cells, which showed an antagonistic effect between iAs and F. In conclusion, endothelial activation and apoptosis induced by iAs and/or F are potential mechanisms in their vascular toxicity. Oxidative stress and impaired NO production are involved in their pro-inflammatory and pro-apoptotic effects.
authors.affiliation: College of Life Science, Shanxi Agricultural University, Taigu, Shanxi 030801, China; Shanxi Key Laboratory of Environmental Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi 030801, China.
authors.forename: Yanqin
authors.initials: Y
authors.lastname: Ma
authors.affiliation: College of Life Science, Shanxi Agricultural University, Taigu, Shanxi 030801, China.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Ma
authors.affiliation: College of Life Science, Shanxi Agricultural University, Taigu, Shanxi 030801, China.
authors.forename: Shuqin
authors.initials: S
authors.lastname: Yin
authors.affiliation: Health Toxicology Department, School of Public Health, Shanxi Medical University, Taiyuan, Shanxi 030001, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Yan
authors.affiliation: Shanxi Key Laboratory of Environmental Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi 030801, China. Electronic address: wangjd53@outlook.com.
authors.forename: Jundong
authors.initials: J
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology; D000077237:Arsenic Trioxide; D001152:Arsenicals; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D005459:Fluorides / Q000633:toxicity*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007249:Inflammation; D015227:Lipid Peroxidation / Q000187:drug effects / Q000276:immunology; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D009569:Nitric Oxide / Q000235:genetics / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects* / Q000276:immunology; D010087:Oxides / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D001152:Arsenicals; D010087:Oxides; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D019255:NADPH Oxidases; D005459:Fluorides; D000077237:Arsenic Trioxide
keywords: Apoptosis; Arsenic; Fluoride; Inflammation; Oxidative stress