Triphenyl phosphate-induced developmental toxicity in zebrafish: potential role of the retinoic acid receptor

Aquatic Toxicology
Gregory M IsalesDavid C Volz

Abstract

Using zebrafish as a model, we previously reported that developmental exposure to triphenyl phosphate (TPP) - a high-production volume organophosphate-based flame retardant - results in dioxin-like cardiac looping impairments that are independent of the aryl hydrocarbon receptor. Using a pharmacologic approach, the objective of this study was to investigate the potential role of retinoic acid receptor (RAR) - a nuclear receptor that regulates vertebrate heart morphogenesis - in mediating TPP-induced developmental toxicity in zebrafish. We first revealed that static exposure of zebrafish from 5-72h post-fertilization (hpf) to TPP in the presence of non-toxic concentrations of an RAR antagonist (BMS493) significantly enhanced TPP-induced toxicity (relative to TPP alone), even though identical non-toxic BMS493 concentrations mitigated retinoic acid (RA)-induced toxicity. BMS493-mediated enhancement of TPP toxicity was not a result of differential TPP uptake or metabolism, as internal embryonic doses of TPP and diphenyl phosphate (DPP) - a primary TPP metabolite - were not different in the presence or absence of BMS493. Using real-time PCR, we then quantified the relative change in expression of cytochrome P450 26a1 (cyp26a1) - a m...Continue Reading

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Citations

Aug 31, 2016·Environmental Science & Technology·David C VolzYinsheng Wang
Dec 14, 2016·Chemical Research in Toxicology·Derik E HaggardRobert L Tanguay
Apr 14, 2017·Environmental Science & Technology·Robin E DodsonJoseph G Allen
Mar 13, 2018·Toxicological Sciences : an Official Journal of the Society of Toxicology·Constance A MitchellDavid C Volz
Aug 2, 2019·Toxicological Sciences : an Official Journal of the Society of Toxicology·Aalekhya ReddamDavid C Volz
Aug 18, 2020·Medicinal Research Reviews·Xiaoxiao YangBinghe Wang
Aug 28, 2020·Neurotoxicology and Teratology·Mathan RameshSathisaran Umamaheswari
Apr 27, 2021·Frontiers in Cell and Developmental Biology·Subham DasguptaRobyn L Tanguay
Sep 12, 2020·Ecotoxicology and Environmental Safety·Kazuki KandaHisato Iwata
Mar 14, 2019·Environmental Science & Technology·Constance A MitchellDavid C Volz

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