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Di (2‐ethylhexyl) phthalate induces cytotoxicity in HEK‐293 cell line, implication of the Nrf‐2/HO‐1 antioxidant pathway
Author(s) -
Amara Ines,
Timoumi Rim,
Graiet Imen,
Ben Salem Intidhar,
Adelou Kamilath,
AbidEssefi Salwa
Publication year - 2019
Publication title -
environmental toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.813
H-Index - 77
eISSN - 1522-7278
pISSN - 1520-4081
DOI - 10.1002/tox.22774
Subject(s) - phthalate , superoxide dismutase , chemistry , oxidative stress , catalase , hek 293 cells , antioxidant , lipid peroxidation , apoptosis , reactive oxygen species , downregulation and upregulation , heme oxygenase , cytotoxicity , microbiology and biotechnology , biochemistry , heme , biology , enzyme , in vitro , organic chemistry , gene
Abstract 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 (ΔΨm) and upregulation of the expression of caspase‐3 mRNA as well as its protein level.