Di-(2-ethylhexyl)-phthalate induces oxidative stress in human endometrial stromal cells in vitro

Cho, Yeon Jean; Park, Seung Bin; Han, Myoungseok

doi:10.1016/j.mce.2015.03.003

Cited by 99 publications

(63 citation statements)

References 35 publications

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“…Exposure of endometrial cells to DEHP at high concentrations (1000 pmol) increased ROS production and decreased the expression of antioxidant enzymes, glutathione peroxidase, heme oxygenase and catalase (Cho et al, 2015) in vitro . Among vinyl chloride workers, urinary MEHP, MEHHP and MEOHP were positively associated with the production of superoxide anion in sperm (Huang et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Urinary phthalate and phthalate alternative metabolites and isoprostane among couples undergoing fertility treatment

Olmsted

Cantonwine

et al. 2017

Environmental Research

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Background Epidemiological data suggest associations between phthalate exposures to a variety of adverse reproductive outcomes including reduced sperm quality and reproductive success. While mechanisms of these associations are not fully elucidated, oxidative stress has been implicated as a potential mediator. We examined associations of urinary metabolites of phthalates and phthalate alternative plasticizers with oxidative stress among couples seeking fertility treatment. Methods Seventeen urinary plasticizer metabolites and 15-F2t isoprostane, a biomarker of oxidative stress, were quantified in spot samples from 50 couples seeking fertility treatment who enrolled in the Sperm Environmental Epigenetics and Development Study during 2014-2015. Results In multivariable analyses, percent change in isoprostane was positively associated with interquartile range increases for the oxidative metabolites of di-2-ethylhexyl phthalate, [mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP; 20.0%, p=0.02), mono-2-ethyl-5-oxohexyl phthalate (MEOHP; 24.1%, p=0.01), and mono-2-ethyl-5-carboxypentyl phthalate (MECPP; 24.1%, p=0.004)], mono-isobutyl phthalate (MiBP; 17.8%, p=0.02), mono-hydroxyisobutyl phthalate (MHiBP; 27.5%, p=0.003), and cyclohexane-1,2-dicarboxylic acid mono-hydroxy-isononyl ester (MHINCH; 32.3%, p=0.002). Stratification of participants by sex revealed that isoprostane was positively associated with MHiBP (41.4%, p=0.01) and monocarboxy-isononyl phthalate (MCNP; 26.0%, p=0.02) among females and MEOHP (35.8%, p=0.03), MiBP (29.2%, p=0.01), MHiBP (34.7%, p=0.007) and MHINCH (49.0%, p=0.002) among males. Conclusions Our results suggest that exposure to phthalates and phthalate replacements are associated with higher levels of oxidative stress in a sex-specific manner. Additional studies are needed to replicate our findings and to examine the potential health implications of the use of phthalates and alternative phthalates in consumer end products.

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Section: Discussionmentioning

confidence: 99%

Urinary phthalate and phthalate alternative metabolites and isoprostane among couples undergoing fertility treatment

Olmsted

Cantonwine

et al. 2017

Environmental Research

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show abstract

Section: Introductionmentioning

confidence: 99%

“…Previous researches have demonstrated, in vitro and in vivo, that DEHP induces cytotoxicity through reactive oxygen species (ROS) generation leading to lipid peroxidation, DNA damage, decrease in the GSH, and significant increase in the activities of superoxide dismutase (SOD), catalase (CAT), and GPx. [13][14][15][16] To reduce ROS formation or to detoxify ROS, physiological systems have involved several adaptive mechanisms that employed antioxidant enzymes or antioxidant compounds. 17 The master cellular sensor for oxidative stress is the nuclear factor (erythroid-derived 2)like 2 (Nrf2).…”

Section: Introductionmentioning

confidence: 99%

Di (2‐ethylhexyl) phthalate induces cytotoxicity in HEK‐293 cell line, implication of the Nrf‐2/HO‐1 antioxidant pathway

Amara

Timoumi

Graiet

et al. 2019

Environmental Toxicology

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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 (ΔΨm) and upregulation of the expression of caspase‐3 mRNA as well as its protein level.

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“…A significant increase in the level of ROS was observed in arrested SOD following MEHP treatment [32]. DEHP increased ROS generation and decreased expression of SOD , glutathione peroxidase (GPX), heme oxygenase (HO), and CAT [33]. Phthalate exposure was also reported to induce oxidative stress and immune related gene expression [34].…”

Section: Discussionmentioning

confidence: 99%

Oxidative Stress-Related Genetic Variants May Modify Associations of Phthalate Exposures with Asthma

Wang

Karmaus

2017

IJERPH

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Background: Phthalate exposure may increase the risk of asthma. Little is known about whether oxidative-stress related genes may alter this association. First, this motivated us to investigate whether genetic polymorphisms of the oxidative-stress related genes glutathione S-transferase Mu 1 (GSTM1), glutathione S-transferase pi 1 (GSTP1), superoxide dismutase 2 (SOD2), catalase (CAT), myeloperoxidase (MPO), and EPHX1 in children are associated with phthalate urine concentrations. Second, we addressed the question whether these genes may affect the influence of phthalates on asthma. Methods: In a case-control study composed of 126 asthmatic children and 327 controls, urine phthalate metabolites (monoethyl phthalate (MEP), monobutyl phthalate (MBP), monobenzyl phthalate (MBzP), and mono(2-ethyl-5-hydroxyhexyl)phthalate (MEHHP) were measured by UPLC-MS/MS at age 3. Genetic variants were analyzed by TaqMan assay. Information on asthma and environmental exposures was also collected. Analyses of variance and logistic regressions were performed. Results: Urine MEHHP levels were associated with asthma (adjusted OR 1.33, 95% CI (1.11–1.60). Children with the GSTP1 (rs1695) AA and SOD2 (rs5746136) TT genotypes had higher MEHHP levels as compared to GG and CC types, respectively. Since only SOD2 TT genotype was significantly associated with asthma (adjusted OR (95% CI): 2.78 (1.54–5.02)), we estimated whether SOD2 variants modify the association of MEHHP levels and asthma. As MEHHP concentrations were dependent on GSTP1 and SOD2, but the assessment of interaction requires independent variables, we estimated MEHHP residuals and assessed their interaction, showing that the OR for SOD2 TT was further elevated to 3.32 (1.75–6.32) when the residuals of MEHHP were high. Conclusions: Urine phthalate metabolite concentrations are associated with oxidative-stress related genetic variants. Genetic variants of SOD2, considered to be reflect oxidative stress metabolisms, might modify the association of phthalate exposure with asthma.

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Di-(2-ethylhexyl)-phthalate induces oxidative stress in human endometrial stromal cells in vitro

Cited by 99 publications

References 35 publications

Urinary phthalate and phthalate alternative metabolites and isoprostane among couples undergoing fertility treatment

Urinary phthalate and phthalate alternative metabolites and isoprostane among couples undergoing fertility treatment

Di (2‐ethylhexyl) phthalate induces cytotoxicity in HEK‐293 cell line, implication of the Nrf‐2/HO‐1 antioxidant pathway

Oxidative Stress-Related Genetic Variants May Modify Associations of Phthalate Exposures with Asthma

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