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Effects of phenobarbital on thyroid hormone contabolism in rat hepatocytes
Citation:
RICHARDSON, V. AND M. J. DEVITO. Effects of phenobarbital on thyroid hormone contabolism in rat hepatocytes. Presented at International Society for the Study of Xenobiotics, Baltimore, MD, October 18 - 22, 2009.
Impact/Purpose:
research results
Description:
Hepatic enzyme inducers such as phenobarbital (PB) decrease circulating thyroid hormone (TH) concentrations in rodents. PB induction of hepatic xenobiotic metabolizing enzymes increases thyroid hormones catabolism and biliary elimination. This study examines the catabolism and clearance of THs by using an in vitro method. Sandwich-cultured hepatocytes from male Sprague-Dawley rats were treated for 72 hours in serum-free media with or without ImM PB. After removal ofmedia, 0.05 uM [t 25]T4, which approximates rat serum TH concentrations, was added to cells and incubated for up to 24 hours at 37C. After 24 hours, media was removed and cell lysates were collected for analysis. After 24 hours, 4.2 and 5.3% of I125T4 accumulated within hepatocytes pretreated with OuM or ImM PB, respectively. To examine the T4 metabolites in media ofPB-treated hepatocytes, the media was analyzed using Ultra High Pressure Liquid Chromatography(UPLC). Eluent from the UPLC was collected on a fraction collector and the fractions were then counted on a gamma counter. T4¬glucuronide (T4G), the most prominent metabolite found in the media of control and PB¬treated hepatocytes, increased 90% with PB treatment. These data suggest that pretreatment with PB increase the accumulation of [I125]T4 into rat hepatocytes and increased the formation of a major metabolite, T4G. The results of this study also demonstrate that rat hepatocytes may be useful for screening thyroid hormone disruptors. (This is an abstract of a proposed presentation and does not necessarily reflect USEPA policy.)