Di (2‐ethylhexyl) phthalate induces cytotoxicity in HEK‐293 cell line, implication of the Nrf‐2/HO‐1 antioxidant pathway
Autor: | Kamilath Adelou, Salwa Abid-Essefi, Ines Amara, Imen Graiet, Rim Timoumi, Intidhar Ben Salem |
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Rok vydání: | 2019 |
Předmět: |
endocrine system
Antioxidant Cell Survival NF-E2-Related Factor 2 Health Toxicology and Mutagenesis medicine.medical_treatment Apoptosis 010501 environmental sciences Management Monitoring Policy and Law Toxicology medicine.disease_cause 01 natural sciences Antioxidants Lipid peroxidation Superoxide dismutase 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Downregulation and upregulation Plasticizers Diethylhexyl Phthalate medicine Humans 0105 earth and related environmental sciences biology Chemistry Phthalate General Medicine Mitochondria Cell biology Oxidative Stress HEK293 Cells Catalase 030220 oncology & carcinogenesis biology.protein Lipid Peroxidation Heme Oxygenase-1 Oxidative stress |
Zdroj: | Environmental Toxicology. 34:1034-1042 |
ISSN: | 1522-7278 1520-4081 |
DOI: | 10.1002/tox.22774 |
Popis: | 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. |
Databáze: | OpenAIRE |
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