Thyroid hormones modulate the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)

These experiments examine the role of thyroxine (T₄) and triiodothyronine (T₃) on the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The first experiment is a continuation of a study reported previously (Rozman et al., 1984). In this experiment, 60 male Sprague-Dawley rats were divided into 6 equal groups. Four groups of rats were thyro’idectomized by 3 mCi Na¹³¹ 1/kg rat. Five weeks later 2 of the thyroidectomized and 1 of the nontbyroidectomized groups of rats received ip 100 μg TCDD/kg body weight in corn oil/acetone, whereas 3 corresponding groups of rats served as vehicle controls. Two days after dosing and every 7 d thereafter, 7 thyroidectomized control group and 1 thyroidectomized TCDD-dosed group were given ip 105 μg T₄/kg body weight. Mortality and body weight were monitored. The course of TCDD toxicity was similar in nonthyroidectomized and thyroidectomized T₄-treated rats but was different in thyroidectomized animals without T₄ replacement therapy. At d 90 after TCDD dosage, mortality was still lower and the mean time to death was increased (p < 0.01) in this group of rats compared to nonthyroidectomized or thyroidectomized T₄-treated rats. However, administration of T₄ starting at d 97 after dosing with TCDD resulted within 2 wk in the same final mortality in thyroidectomized rats as in nonthyroidectomized or thyroidectomized T₄-treated animals, indicating that thyroid hormones modulate the time course of the wasting syndrome but do not affect the ultimate mortality figure. Body weight loss was much slower in thyroidectomized (-1 g/d) than in nonthyroidectomized or thyroidectomized T₄ -treated rats (-8 g/d). In the second experiment the three vehicle control groups of the first experiment were used. Nonthyroidectomized vehicle controls and thyroidectomized T₄-treated controls were maintained as before, whereas thyroidectomized controls received T₃ at 5μg/kg daily. One month later each rat was dosed with TCDD at 100 μg/kg in corn oil/acetone. Toxicity of TCDD was similar in nonthyroidectomized, thyroidectomized T₄-treated, and thyroidectomized T₃-treated rats as judged by mortality, body weight, and food bintake, indicating no difference between T₃ and T₄ in the modulation of TCDD toxicity.