In vitro endocrine disruption potential of organophosphate flame retardants via human nuclear receptors

Kojima, Hiroyuki; Takeuchi, Shinji; Itoh, Toshihiro; Iida, Mitsuru; Kobayashi, Satoshi; Yoshida, Toshihide

doi:10.1016/j.tox.2013.09.004

Cited by 311 publications

(177 citation statements)

References 37 publications

Supporting

Mentioning

166

Contrasting

Unclassified

Order By: Relevance

“…However, our results were different from those of a previously reported in vitro study, which showed that several OPEs, including TDCPP, had no TR activity (Kojima et al, 2013). By examining the experimental details of this study, we realized that the cell line, expression plasmids and transfection reagent used in the previous study were different from those used in the current study, and may have led to the observed differences in the results.…”

Section: Discussioncontrasting

confidence: 99%

“…According to the results of previous studies, TR pathway appears to be interfered by OPEs. To the best of our knowledge, there has been only one paper reported in the literature pertaining to the activities of OPEs towards the human TR, where none of the test compounds showed any agonistic or antagonistic activity (Kojima et al, 2013). Given that different results were obtained from different studies, such as the conflicting results described above for the activities of OPEs towards the ER and PPARγ, it is still necessary to study the effects of OPEs towards the TR to determine the toxicity mechanisms of these compounds.…”

Section: J O U R N a L O F E N V I R O N M E N T A L S C I E N C E Smentioning

confidence: 99%

“…The results of two recent studies suggested that some of these OPE compounds could exert their toxicity via the activation of the peroxisome proliferator-activated receptor (PPARγ) pathway (Belcher et al, 2014;Fang et al, 2015). Furthermore, Kojima et al (2013) evaluated the effects of OPEs against eight human nuclear receptor pathways and found that four of these pathways were affected by the OPEs:ER agonistic activity, androgen receptor antagonistic activity, glucocorticoid receptor antagonistic activity and PXR agonistic activity. No effects were observed for the other four nuclear receptor pathways (thyroid hormone receptor (TR), retinoic acid receptor (RAR), retinoid X receptor (RXR) and PPARγ) (Kojima et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, Kojima et al (2013) evaluated the effects of OPEs against eight human nuclear receptor pathways and found that four of these pathways were affected by the OPEs:ER agonistic activity, androgen receptor antagonistic activity, glucocorticoid receptor antagonistic activity and PXR agonistic activity. No effects were observed for the other four nuclear receptor pathways (thyroid hormone receptor (TR), retinoic acid receptor (RAR), retinoid X receptor (RXR) and PPARγ) (Kojima et al, 2013). Given that the data obtained to date remain scattered and sometimes contradictory, further work is required to understand the disruptive impact of OPEs on the nuclear receptor pathways.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

In vitro assessment of thyroid hormone receptor activity of four organophosphate esters

Ren

Cao

Yang

et al. 2016

Journal of Environmental Sciences

View full text Add to dashboard Cite

Previous animal experiments have implied that organophosphate esters (OPEs) have a disruption effect on the thyroid endocrine system. However, knowledge of the toxicological mechanism remains limited. In this study, the activities of four OPEs have been characterized against the thyroid hormone (TH) nuclear receptor (TR) using two in vitro models, with the aim of evaluating their toxicity mechanisms towards the TR. The results of a TH-dependent cell proliferation assay showed that tris(2-chloro-1-(chloromethyl)ethyl)phosphate (TDCPP) could induce cell growth, while the other three OPEs had no effect. The results of a luciferase reporter gene assay revealed that all four of the OPEs tested in the current study showed agonistic activity towards TRβ, with TDCPP being the most potent one. Moreover, molecular docking revealed that all the tested OPEs could fit into the ligand binding pocket of TRβ, with TDCPP binding more effectively than the other three OPEs. Taken together, these data suggest that OPEs might disrupt the thyroid endocrine system via a mechanism involving the activation of TR.

show abstract

Section: Discussioncontrasting

confidence: 99%

Section: J O U R N a L O F E N V I R O N M E N T A L S C I E N C E Smentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

In vitro assessment of thyroid hormone receptor activity of four organophosphate esters

Ren

Cao

Yang

et al. 2016

Journal of Environmental Sciences

View full text Add to dashboard Cite

show abstract

“…In vitro reporter gene assays showed that TDCPP has potential endocrine-disrupting effects and can act as an androgen receptor (AR) antagonist (Kojima et al, 2013 (McGee et al, 2012;Fu et al, 2013;Liu et al, 2013a), including thyroid endocrine-disruption activity, as it reduced the levels of circulating T4 levels in zebrafish larvae (Wang et al, 2013). Moreover, in cultured chicken embryos TDCPP caused altered expression of TH-responsive genes (Crump et al, 2012;Farhat et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Bioconcentration, metabolism and neurotoxicity of the organophorous flame retardant 1,3-dichloro 2-propyl phosphate (TDCPP) to zebrafish

et al. 2015

View full text Add to dashboard Cite

Gestational triphenyl phosphate exposure in C57Bl/6 mice perturbs expression of insulin‐like growth factor signaling genes in maternal and fetal liver

Philbrook

Restivo

Belanger

et al. 2018

Birth Defects Research

View full text Add to dashboard Cite

Triphenyl phosphate (TPhP) is an organophosphorus flame retardant and plasticizer that has been added to numerous consumer products in recent years. TPhP is not overtly toxic, however recent studies have suggested that it may have metabolic disrupting effects following developmental exposure. The present study aimed to investigate the developmental and potential metabolic effects of TPhP in a murine model. C57Bl/6 dams were exposed on gestational days (GD) 8, 10, 12, and 14 to 0, 5, 25, or 50 mg/kg TPhP via intraperitoneal injection. Dams were euthanized on GD19, maternal organs excised and weighed, fetal measurements taken, and maternal and fetal livers retained for analysis. A significant increase in placenta size of TPhP exposed mice was found. Maternal and fetal liver gene expression of insulin-like growth factor (Igf) 1 and 2, as well as downstream genes involved in Igf signaling were measured. Additionally, Igf1 protein levels were measured in both maternal and fetal liver. A significant decrease in transcript levels of Igf1 and Irs2 was detected in maternal livers, whereas a significant increase in transcript levels of all genes measured was detected in fetal liver. A significant decrease in Igf1 protein levels was detected in maternal liver, however the increase in Igf1 protein levels in fetal livers was not found to be statistically significant. These results support previous findings that TPhP does not cause overt structural developmental toxicity. These data also support the hypothesis that TPhP could disrupt maternal and fetal metabolism, justifying the need for follow-up studies to investigate further.

show abstract

In vitro endocrine disruption potential of organophosphate flame retardants via human nuclear receptors

Cited by 311 publications

References 37 publications

In vitro assessment of thyroid hormone receptor activity of four organophosphate esters

In vitro assessment of thyroid hormone receptor activity of four organophosphate esters

Bioconcentration, metabolism and neurotoxicity of the organophorous flame retardant 1,3-dichloro 2-propyl phosphate (TDCPP) to zebrafish

Gestational triphenyl phosphate exposure in C57Bl/6 mice perturbs expression of insulin‐like growth factor signaling genes in maternal and fetal liver

Contact Info

Product

Resources

About