Differential Nephrotoxicity of Three Brominated Flame Retardants in Rat and Human Renal Cells

Abstract

Brominated flame retardants (BFRs) are a class of 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 have been reported 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. Previous research shows that these compounds cause nephrotoxicity in rats and mice; however, the mechanisms mediating this nephrotoxicity are unknown. In the present study, we determined the effects of TBBPA, HBCD, and BDE 47 on cell viability in rat (NRK), human embryonic (HEK‐293), and adult human (HK‐2) kidney cells after 48 hours. We observed a concentration‐ and species‐dependent effect on MTT staining, with IC50 values of 58, 38, and 3 μM for TBBPA; 20, 16, and 7 μM for HBCD; and 46, 40, and 14 μM for BDE 47 in NRK, HEK‐293, and HK‐2 cells, respectively. We assessed the mechanisms of cell death by measuring annexin V staining and propidium iodide (PI) staining as markers of apoptosis and necrosis, and by studying changes in nuclear morphology via DAPI staining. Significant increases in both the percentage of annexin V‐positive cells and the percentage of annexin V and PI double‐positive cells suggested that all compounds were inducing apoptosis. These data suggest that BFRs induce species‐dependent toxicity in renal cells, with higher levels of toxicity being induced in human cells. The mechanisms mediating this differential toxicity is the subject of future studies.Support or Funding InformationThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.