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Effects on 2,2’,4,4’-Tetrabromodiphenyl ether (BDE 47) on Thyroxine Metabolism and Transport in Primary Rat and Human Hepatocytes
Citation:
Richardson, V. AND Chris Mazur. Effects on 2,2’,4,4’-Tetrabromodiphenyl ether (BDE 47) on Thyroxine Metabolism and Transport in Primary Rat and Human Hepatocytes. Society of Toxicology Annual Meeting, New Orleans, LA, March 13 - 17, 2016.
Impact/Purpose:
To present at Society of Toxicology 2015
Description:
Polybrominated diphenyl ethers (PBDEs), a major class of brominated flame retardants, are used in consumer products including furniture, electronics, textiles, and plastics. PBDEs bioaccumulate in wildlife and humans; BDE 47 is the predominant PBDE congener detected and typically accounts for ~half of total tissue PBDEs. They act as endocrine disruptors through interference with thyroid hormone (TH) homeostasis. Although consequences of exposure to humans have not been determined, PBDE-mediated decreases in TH profoundly affect developing rodents. PBDE-mediated decreases in THs are linked to the induction of hepatic uridinediphosphate- glucuronosyltransferases (UGTs) in rodents. It is not certain that metabolism alone mediates the effects of PBDEs on circulating TH concentrations as PBDEs increase the expression of genes involved not only in TH metabolism but also TH transport. In this study, we used primary rat and human hepatocytes to examine the effects of BDE 47 on hepatic metabolism and uptake of thyroxine (T4) and the role these mechanisms may play in TH disruption. Hepatocytes from human or Sprague-Dawley rats were treated (72 hours) with BDE 47 (0 or 30 uM). Medium was removed and replaced with 0.05 or 0.1 uM T4 (rat or human median serum concentration, respectively). Cells were collected after 30 seconds to measure T4 uptake and media was collected after 24 hours to measure T4-glucuronide (T4G). Medium and cells were analyzed by liquid chromatography. In untreated hepatocytes, T4G in the medium of rats was ~20-times greater than in the medium of humans. Following BDE 47 exposure, T4G in the medium of rat hepatocytes was unchanged; however, T4G in the medium of human hepatocytes increased ~2-fold. T4 uptake into rat and human hepatocytes was unchanged following BDE 47 exposure. The data do not show significant BDE 47-mediated alteration in active transport of T4 in rat and human hepatocytes, but do show significant species differences in hepatic UGT activity toward T4. (This abstract does not reflect US EPA policy.)