Effect of PCB 126 on liver enzymes and the thyroid axis in the male rat
Almekinder, Tara Lyn
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PCB 126 is known to interfere with thyroid hormone (TH) homeostasis by inducing microsomal enzymes and perturbing thyroid hormones. The aim of the present study is to evaluate the temporal effects of PCB 126 (3, 3’, 4, 4’, 5-pentachlorobiphenyl) on the thyroid axis, as mediated by induction of liver cytochrome P450 (total P450 and CYP1A1). A pharmacodynamic model for PCB 126-induced effects on the thyroid axis is under development in our laboratories. Adult male Sprague-Dawley rats were administered a single oral bolus dose of 0, 7.5, 75, or 275 ug PCB 126/kg bw dissolved in corn oil. The rats were sacrificed periodically over 59 days for evaluation. PCB 126 caused a dose-related decrease in body weight gain. Total P450 levels were elevated for 59, 22, and 5 days for the 275, 75, and 7.5 ug/kg dosage groups, respectively. Ethoxyresorufin-O-deethylase (EROD) activity, a marker for CYP1A1, was increased for 1, 5, and 35 days in the 7.5, 75, and 275ug/kg groups, respectively. Serum thyroxine (T4) and triiodothyronine (T3), reverse T3 (rT3), and thyroid stimulating hormone (TSH) were measured by radioimmunoassay. Free T4, the active unbound form, was measured by direct equilibrium dialysis. PCB decreased Total T4 compared to controls at days 1, 5, 9 and 22. Free T4 was decreased throughout the study period. Total T3 and reverse T3 (rT3) showed no discernable trend by dosing. TSH was increased through day 9 and 22 day period compared to control levels. Thyroid glands were analyzed histologically for altered colloid/epithelial ratios on days 20, 35, and 59 at all doses measured. Hepatic Type 1 5’-deiodinase activity was decreased in a dose-related fashion throughout the study. These data demonstrate that PCB 126 interferes with thyroid homeostasis with reduction of free T4 persistent for at least 59 days after dosing.