Thyroid Disruption by Di-n-Butyl Phthalate DBP and Mono-n-Butyl Phthalate MBP in Xenopus laevisReport as inadecuate




Thyroid Disruption by Di-n-Butyl Phthalate DBP and Mono-n-Butyl Phthalate MBP in Xenopus laevis - Download this document for free, or read online. Document in PDF available to download.

Background

Di-n-butyl phthalate DBP, a chemical widely used in many consumer products, is estrogenic and capable of producing seriously reproductive and developmental effects in laboratory animals. However, recent in vitro studies have shown that DBP and mono-n-butyl phthalate MBP, the major metabolite of DBP, possessed thyroid hormone receptor TR antagonist activity. It is therefore important to consider DBP and MBP that may interfere with thyroid hormone system.

Methodology-Principal Findings

Nieuwkoop and Faber stage 51 Xenopus laevis were exposed to DBP and MBP 2, 10 or 15 mg-L separately for 21 days. The two test chemicals decelerated spontaneous metamorphosis in X. laevis at concentrations of 10 and 15 mg-L. Moreover, MBP seemed to possess stronger activity. The effects of DBP and MBP on inducing changes of expression of selected thyroid hormone response genes: thyroid hormone receptor-beta TRβ, retinoid X receptor gamma RXRγ, alpha and beta subunits of thyroid-stimulating hormone TSHα and TSHβ were detected by qPCR at all concentrations of the compounds. Using mammalian two-hybrid assay in vitro, we found that DBP and MBP enhanced the interactions between co-repressor SMRT silencing mediator for retinoid and thyroid hormone receptors and TR in a dose-dependent manner, and MBP displayed more markedly. In addition, MBP at low concentrations 2 and 10 mg-L caused aberrant methylation of TRβ in head tissue.

Conclusions

The current findings highlight potential disruption of thyroid signalling by DBP and MBP and provide data for human risk assessment.



Author: Ouxi Shen , Wei Wu , Guizhen Du, Renping Liu, Lugang Yu, Hong Sun, Xiumei Han, Yi Jiang, Wei Shi, Wei Hu, Ling Song, Yankai Xia,

Source: http://plos.srce.hr/



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