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Acute in vitro Nephrotoxicity of Three Brominated Flame Retardants
Author(s) -
Barnett Lillie,
Cummings Brian S.
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.03345
Subject(s) - propidium iodide , tetrabromobisphenol a , polybrominated diphenyl ethers , toxicity , chemistry , brominated flame retardant , nephrotoxicity , apoptosis , viability assay , fire retardant , annexin , kidney , programmed cell death , pharmacology , microbiology and biotechnology , biology , biochemistry , pollutant , endocrinology , organic chemistry
Brominated flame retardants (BFRs) are organohalogens commonly added to commercial products such as computers, electronics, textiles and furniture to reduce their flammability. BFRs have significant environmental persistence and are reported to be detected in human blood and breastmilk. In particular, tetrabromobisphenol A (TBBPA), hexabromocyclododecane (HBCD), and polybrominated diphenyl ethers (PBDEs) occupy nearly 20 percent of the global flame retardant market and are suggested to have adverse effects on humans and wildlife. As such, the mechanisms of BFR‐induced toxicity are actively being explored under the U.S. EPA Toxic Substance Control Act. We previously determined the effects of TBBPA, HBCD, and BDE 47 on cell viability in rat (NRK 52E), adult human (HK‐2 and RPTEC), and human embryonic (HEK‐293) kidney cells after 48 hours, and demonstrated that these compounds induce concentration‐dependent effects on MTT staining. Assessment of the mechanism of cell death using annexin V staining and propidium iodide (PI) staining showed that all three compounds induce apoptosis in these cells. We subsequently performed RNAseq and pathway analysis in these cells to identify key signaling pathways involved in the mechanism of BFR‐induced toxicity. Furthermore, we explored how BFR nephrotoxicity impacts neighboring cells by treating human fibroblasts with conditioned media from BFR‐treated kidney cells and measuring morphological, molecular, and functional changes in fibroblast activation using RT‐PCR, wound healing and high content image analysis. Ultimately, these data will aid future studies concerning the molecular mechanisms of BFR toxicity in kidney cells and how this impacts kidney epithelia‐fibroblast crosstalk using chronic exposure at environmentally relevant doses.