Arsenic and fluoride induce apoptosis, inflammation and oxidative stress in cultured human umbilical vein endothelial cells

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 As2O3 and/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.