The combined effects of DEHP and PCBs on phospholipase in the livers of mice

Lin, Yi; Huang, Qiansheng; Chen, Yajie; Fang, Chao; Sun, Xia; Dong, Shuang

doi:10.1002/tox.21885

Cited by 11 publications

(7 citation statements)

References 31 publications

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“…It has been shown that E 2 and benzophenone-2 (weak xenoestrogen) decrease in expression of Ahr mRNA in pituitary, thyroid, and uterus female Sprague–Dawley rats (Schlecht et al 2004 ). Similar trend was observed by Lin et al ( 2015b ) where combined exposure of the mice to DEHP and Aroclor 1254 slightly but not significantly decrease expression of AhR mRNA expression in animal liver (Lin et al 2015b ). Furthermore, DEHP decrease in Cyp1a1 activity in rat liver (Seo et al 2004 ).…”

Section: Discussionsupporting

confidence: 84%

The Action of Di-(2-Ethylhexyl) Phthalate (DEHP) in Mouse Cerebral Cells Involves an Impairment in Aryl Hydrocarbon Receptor (AhR) Signaling

et al. 2018

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Di-(2-ethylhexyl) phthalate (DEHP) is used as a plasticizer in various plastic compounds, such as polyvinyl chloride (PVC), and products including baby toys, packaging films and sheets, medical tubing, and blood storage bags. Epidemiological data suggest that phthalates increase the risk of the nervous system disorders; however, the impact of DEHP on the brain cells and the mechanisms of its action have not been clarified. The aim of the present study was to investigate the effects of DEHP on production of reactive oxygen species (ROS) and aryl hydrocarbon receptor (AhR), as well as Cyp1a1 and Cyp1b1 mRNA and protein expression in primary mouse cortical neurons and glial cells in the in vitro mono-cultures. Our experiments showed that DEHP stimulated ROS production in both types of mouse neocortical cells. Moreover, the results strongly support involvement of the AhR/Cyp1A1 signaling pathway in the action of DEHP in neurons and glial cells. However, the effects of DEHP acting on the AhR signaling pathways in these two types of neocortical cells were different. In neurons, AhR mRNA expression did not change, but AhR protein expression decreased in response to DEHP. A similar trend was observed for Cyp1a1 and Cyp1b1 mRNA and protein expression. Failure to induce Cyp1a1 in neurons was confirmed by EROD assay. In primary glial cells, a decrease in AhR protein level was accompanied by a decrease in AhR mRNA expression. In glial cells, mRNA and protein expression of Cyp1a1 as well as Cyp1a1-related EROD activity were significantly increased. As for Cyp1b1, both in neurons and glial cells Cyp1b1 mRNA expression did not significantly change, whereas Cyp1b1 protein level were decreased. We postulate that developmental exposure to DEHP which dysregulates AhR/Cyp1a1 may disrupt defense processes in brain neocortical cells that could increase their susceptibility to environmental toxins.

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Section: Discussionsupporting

confidence: 84%

The Action of Di-(2-Ethylhexyl) Phthalate (DEHP) in Mouse Cerebral Cells Involves an Impairment in Aryl Hydrocarbon Receptor (AhR) Signaling

et al. 2018

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“…These studies also reported significant alterations of the hepatic gene signature consistent with the liver being the primary site for detoxification (Table 1 ). Interestingly, whenever males and females have been studied, sex-differences have also been observed ( 35 , 40 , 41 ) as compiled (Table 1 ) which highlights the necessity, as mandated by the National Institutes of Health (NIH), to consider sex as a biological variable ( 49 ). Also consistent with our data ( 34 , 37 ), it was shown that the nutritional component was as well a variable to consider.…”

Section: Evidences For a Cocktail Effect From Natural Or Artificial Mmentioning

confidence: 99%

“…Other combinations of low-dosed pollutants in mixture have later been tested in mouse ( 35 , 38 , 40 ) or rat ( 41 ) models as well as in juvenile seabream ( 36 ). These studies also reported significant alterations of the hepatic gene signature consistent with the liver being the primary site for detoxification (Table 1 ).…”

Section: Evidences For a Cocktail Effect From Natural Or Artificial Mmentioning

confidence: 99%

Environmental Pollutants and Metabolic Disorders: The Multi-Exposure Scenario of Life

Magueresse-Battistoni

Vidal

Naville

2018

Front. Endocrinol.

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Obesity and diabetes have reached epidemic proportions the past few decades and continue to progress worldwide with no clear sign of decline of the epidemic. Obesity is of high concern because it is the main risk factor for a number of non-communicable diseases such as cardiovascular diseases and type 2 diabetes. Metabolic diseases constitute a major challenge as they are associated with an overall reduced quality of life and impose a heavy economic burden on countries. These are multifactorial diseases and it is now recognized that environmental exposure to man-made chemical pollutants is part of the equation. Yet, risk assessment procedures are based on a one-by-one chemical evaluation which does not meet the specificities of the multi-exposure scenario of life, e.g., a combined and long-term exposure to even the smallest amounts of chemicals. Indeed, it is assumed that environmental exposure to chemicals will be negligible based on the low potency of each chemical and that they do not interact. Within this mini-review, strong evidences are brought that exposure to low levels of multiple chemicals especially those shown to interfere with hormonal action, the so-called endocrine disrupting compounds do trigger metabolic disturbances in conditions in which no effect was expected if considering the concentration of each individual chemical in the mixture. This is known as the cocktail effect. It means that risk assessment procedures are not protective enough and thus that it should be revisited for the sake of Public Health.

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“…Chemical mixtures extracted from natural water could also disturb the function of steroid hormones where PPARs act as key regulators [ 82 , 83 ]. In our study, cotreatment with DEHP and PCBs promoted the expression of PPAR γ but not the other PPAR types in mice liver [ 84 ].…”

Section: Environmental Chemicals As Exogenous Ligandsmentioning

confidence: 99%

Mediating Roles of PPARs in the Effects of Environmental Chemicals on Sex Steroids

Huang

Chen

2017

PPAR Research

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Peroxisome proliferator-activated receptors (PPARs) are ligand-activated nuclear receptors that are widely involved in various physiological functions. They are widely expressed through the reproductive system. Their roles in the metabolism and function of sex steroids and thus the etiology of reproductive disorders receive great concern. Various kinds of exogenous chemicals, especially environmental pollutants, exert their adverse impact on the reproductive system through disturbing the PPAR signaling pathway. Chemicals could bind to PPARs and modulate the transcription of downstream genes containing PPRE (peroxisome proliferator response element). This will lead to altered expression of genes related to metabolism of sex steroids and thus the abnormal physiological function of sex steroids. In this review, various kinds of environmental ligands are summarized and discussed. Their interactions with three types of PPARs are classified by various data from transcript profiles, PPRE reporter in cell line, in silico docking, and gene silencing. The review will contribute to the understanding of the roles of PPARs in the reproductive toxicology of environmental chemicals.

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The combined effects of DEHP and PCBs on phospholipase in the livers of mice

Cited by 11 publications

References 31 publications

The Action of Di-(2-Ethylhexyl) Phthalate (DEHP) in Mouse Cerebral Cells Involves an Impairment in Aryl Hydrocarbon Receptor (AhR) Signaling

The Action of Di-(2-Ethylhexyl) Phthalate (DEHP) in Mouse Cerebral Cells Involves an Impairment in Aryl Hydrocarbon Receptor (AhR) Signaling

Environmental Pollutants and Metabolic Disorders: The Multi-Exposure Scenario of Life

Mediating Roles of PPARs in the Effects of Environmental Chemicals on Sex Steroids

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