4.7 Article

Effects of DEHP, DEHT and DINP Alone or in a Mixture on Cell Viability and Mitochondrial Metabolism of Endothelial Cells In Vitro

Journal

TOXICS
Volume 10, Issue 7, Pages -

Publisher

MDPI
DOI: 10.3390/toxics10070373

Keywords

DEHP; DEHT; DINP; mixture effects; human microvascular endothelial cells; in vitro; mitochondrial dysfunction

Funding

  1. University of Rouen Normandy
  2. Regional Council of Normandy

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Plasticizers have adverse effects on endothelial cells, disrupting both cellular function and mitochondrial function. However, endothelial cells may undergo metabolic adaptation to combat the cellular stress induced by plasticizers.
Plasticizers are chemicals in high demand, used in a wide range of commercial products. Human are exposed through multiple pathways, from numerous sources, to multiple plasticizers. This is a matter of concern, as it may contribute to adverse health effects. The vascular system carries plasticizers throughout the body and therefore can interact with the endothelium. The aim of the study was to evaluate the in vitro toxicity on endothelial cells by considering the individual and the mixture effects of bis-(2-ethylhexyl) phthalate (DEHP), diisononyl phthalate (DINP) or bis-(2-ethylhexyl) terephthalate (DEHT). In this study, their cytotoxicity on HMEC-1 cells was evaluated on cell function (viability, cell counting, total glutathione and intracellular adenosines) and mitochondrial function (mitochondrial respiration). Results showed cellular physiological perturbations induced with all the condition tested, excepted for DEHT. Plasticizers induced a cytotoxicity by targeting mitochondrial respiration, depleting mitochondrial ATP production and increasing glycolytic metabolism. Additionally, delayed effects were observed between the cellular and the mitochondrial parameters. These results suggest that endothelial cells could go through a metabolic adaptation to face plasticizer-induced cellular stress, to effectively maintain their cellular processes. This study provides additional information on the adverse effects of plasticizers on endothelial cells.

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