Oxidative DNA damage induced by di-(2-ethylhexyl) phthalate in HEK-293 cell line

Wang, Xuan; Jiang, Lijie; Ge, Lan; Chen, Min; Yang, Guang; Ji, Fang; Zhong, Laifu; Guan, Yingjie; Liu, Xiaofang

doi:10.1016/j.etap.2015.03.016

Cited by 36 publications

(14 citation statements)

References 42 publications

(43 reference statements)

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“…This could partly explain the DNA fragmentation observed in our work after DEHP treatment. Similar results have been reported in Human embryonic kidney 293 cells (HEK‐293) cells treated with DEHP, which showed that this phthalate induced oxidative DNA damage …”

Section: Discussionsupporting

confidence: 85%

Di (2‐ethylhexyl) phthalate targets the thioredoxin system and the oxidative branch of the pentose phosphate pathway in liver of Balb/c mice

Amara

Timoumi

Annabi

et al. 2019

Environmental Toxicology

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Di (2-ethylhexyl) phthalate (DEHP) is a plasticizer that gives flexibility to various polyvinyl chloride products. It is a pollutant easily released into the environment and can cause many adverse effects to living organisms including hepatotoxicity. The thioredoxin system is a determining factor in the redox balance maintaining in the liver, which is a vulnerable tissue of reactive oxygen species overproduction because of its high energy needs. In order to determine if the thioredoxin system is a target in the development of DEHP hepatotoxicity, Balb/c mice were administered with DEHP intraperitoneally daily for 30 days. Results demonstrated that after DEHP exposure, biochemical profile changes were observed. This phthalate causes oxidative damage through the induction of lipid peroxydation as well as the increase of superoxide dismutase and catalase activities. As new evidence provided in this study, we demonstrated that the DEHP affected the thioredoxin system by altering the expression and the activity of thioredoxin (Trx) and thioredoxin Reductase (TrxR1). The two enzyme activities of the oxidative phase of the pentose phosphate pathway:Glucose-6-phosphate dehydrogenase and 6-Phosphogluconate dehydrogenase were also affected by this phthalate. This leads to a decrease in the level of nicotinamide adenine dinucleotide phosphate used by the TrxR1 to maintain the regeneration of the reduced Trx. We also demonstrated that such effects can be responsible of DEHP-induced DNA damage. K E Y W O R D S di (2-ethylhexyl) phthalate, DNA damage, oxidative stress, pentose phosphate pathway, thioredoxin system 1 | INTRODUCTION Di (2-ethylhexyl) phthalate (DEHP) is an organic compound abundantly used as a plasticizer to soften and increase the flexibility ofplastic. It has aroused public concern since the large mass of DEHPbased product frequently used like food packaging, cosmetics, perfumes, and medical devices. 1 Due to its low covalent binding to plastic polymers, DEHP can migrate from plastic matrix to foods, beverages, and even in a direct way in body fluids. 2 Therefore, exposure to this phthalate appears to be inevitable and humans may be exposed to it through digestive system and skin absorption or via inhalation. Nakamiya et al 3 reported that human body introduces around 25 mg of DEHP every day only from food. It was found that DEHP concentrations are approximately 25 mg/kg in cheese, 158 mg/kg in oily

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Section: Discussionsupporting

confidence: 85%

Di (2‐ethylhexyl) phthalate targets the thioredoxin system and the oxidative branch of the pentose phosphate pathway in liver of Balb/c mice

Amara

Timoumi

Annabi

et al. 2019

Environmental Toxicology

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“…1 Di-(2-ethylhexyl) Phthalate (DEHP) is a conventional plasticizer used for providing flexibility to polyvinyl chloride. 2 The ester is omnipresent in nature as a synthetic pollutant from industrial and municipal sewages, posing severe health risks, including mutations and carcinomas due to DNA damage as a consequence of enhanced production of reactive oxygen species and free radicals 3,4 ; cell cycle arrest by inhibition of DNA synthesis at the S phase 5 ; impairment of liver, lungs, kidney, heart, and reproductive organs etc. 6 Moreover, serious complications related to cognitive/behavioral development have reported in children and even neonates stemming from disruption of endocrine pathways under extreme DEHP exposure.…”

Section: Introductionmentioning

confidence: 99%

Computational optimization of in vitro parameters for di‐(2‐ethylhexyl) phthalate production from Anabaena circinalis

Sarkar¹,

Andavan²

2018

J of Cellular Biochemistry

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Di-(2-ethylhexyl) phthalate (DEHP) is a ubiquitous environmental toxicant, and finds extensive commercial application as a plasticizer to reduce the rigidity of polyvinyl chloride. Besides numerous negative impacts on environment and public health, the compound exhibits acute bioactivity against microbes and has therapeutic value too. Considering this biochemical significance, searching of its new biogenic sources has become an active area of research. Here, DEHP is identified from the biomass of a toxic strain of Anabaena circinalis, which is quite unobvious, and simultaneously, the in vitro physical conditions are optimized by using a swarm-based multiparameter optimization technique. A purified fraction collected from column chromatography is subjected to gas chromatography (GC) to fetch the compound peak and then subsequent mass analysis for its identification. The mass spectrum describes the molecular weight along with the structure of DEHP with 99.9% experimental accuracy. An experimental observation table has been used to frame a fitness function using the curve fitting approach when temperature (T), light and dark period (LD), and duration of subculture cycle (DSC) are considered as the target parameters to be optimized. The optimum values obtained for T, LD, and DSC are 20°C, 14:10 hour light and dark ratio approximately, and 40 days, respectively. This experimental finding of A. circinalis FSS 124 as a novel source of DEHP and subsequent optimization using soft computing tools might be a benchmark for process optimization in biological research.

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“…Accordingly, we moved on to investigate the ReactAlphaLISA assay in cell media as a simple phenotypic screen of cellular MG levels. HEK293 cells were grown in low and high glucose media while treated with 0–150 μM buthionine sulfoximine (BSO), an inhibitor of GSH synthesis, which has been shown to reduce GSH levels in HEK293 cells [31]. GSH reacts spontaneously with MG generating the hemithioacetal substrate for GLO1, thus reduced MG detoxification and increased MG levels were expected in response to BSO treatment.…”

Section: Resultsmentioning

confidence: 99%

ReactELISA method for quantifying methylglyoxal levels in plasma and cell cultures

et al. 2019

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Methylglyoxal (MG) is a toxic glycolytic by-product associated with increased levels of inflammation and oxidative stress and has been linked to ageing-related diseases, such as diabetes and Alzheimer's disease. As MG is a highly reactive dicarbonyl compound, forming both reversible and irreversible adducts with a range of endogenous nucleophiles, measuring endogenous levels of MG are quite troublesome. Furthermore, as MG is a small metabolite it is not very immunogenic, excluding conventional ELISA for detection purposes, thus only more instrumentally demanding LC-MS/MS-based methods have demonstrated convincing quantitative data. In the present work we develop a novel bifunctional MG capture probe as well as a high specificity monoclonal antibody to finally setup a robust reaction-based ELISA (ReactELISA) method for detecting the highly reactive and low-level (nM) metabolite MG in human biological specimens. The assay is tested and validated against the current golden standard LC-MS/MS method in human blood plasma and cell-culture media. Furthermore, we demonstrate the assays ability to measure small perturbations of MG levels in growth media caused by a small molecule drug buthionine sulfoximine (BSO) of current clinical relevance. Finally, the assay is converted into a homogenous (no-wash) AlphaLISA version (ReactAlphaLISA), which offers the potential for operationally simple screening of further small molecules capable of perturbing cellular MG. Such compounds could be of relevance as probes to gain insight into MG metabolism as well as drug-leads to alleviate ageing-related diseases.

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Oxidative DNA damage induced by di-(2-ethylhexyl) phthalate in HEK-293 cell line

Cited by 36 publications

References 42 publications

Di (2‐ethylhexyl) phthalate targets the thioredoxin system and the oxidative branch of the pentose phosphate pathway in liver of Balb/c mice

Di (2‐ethylhexyl) phthalate targets the thioredoxin system and the oxidative branch of the pentose phosphate pathway in liver of Balb/c mice

Computational optimization of in vitro parameters for di‐(2‐ethylhexyl) phthalate production from Anabaena circinalis

ReactELISA method for quantifying methylglyoxal levels in plasma and cell cultures

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