Journal
ENVIRONMENTAL TOXICOLOGY
Volume 34, Issue 9, Pages 1034-1042Publisher
WILEY
DOI: 10.1002/tox.22774
Keywords
apoptosis; di (2-ethylhexyl) phthalate; Nrf2; HO-1 antioxidant pathway; oxidative stress
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Funding
- Ministere Tunisien de l'Enseignement Superieure et de la Recherche Scientifique et de la Technologie
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The di (2-ethylhexyl) phthalate (DEHP) is a plasticizer used in the polyvinyl chloride industry. Human exposure to this plasticizer is inevitable and contributes to several side effects. In this study, we examined whether DEHP induces apoptosis and oxidative stress in embryonic kidney cells (HEK-293) and whether the nuclear factor E2-related factor 2 (Nrf-2)/heme oxygenase-1 (HO-1) antioxidant pathway is involved in the pathogenesis of this process. We demonstrated that DEHP is cytotoxic to HEK-293 cells. It causes oxidative damage through the generation of free radicals, induces lipid peroxidation, and alters superoxide dismutase and catalase activities. Simultaneously, DEHP treatment decreases the expression and the protein level of Nrf-2 and HO-1. Inhibition of the Nrf-2/HO-1 pathway is related to the mitochondrial pathway of apoptosis. This apoptotic process is characterized by a loss of mitochondrial transmembrane potential (Delta psi m) and upregulation of the expression of caspase-3 mRNA as well as its protein level.
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