Kleiman de Pisarev D L, Rios de Molina M C, San Martin de Viale L C
Departmento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Núñez, Argentina.
Biochem Pharmacol. 1990 Mar 1;39(5):817-25. doi: 10.1016/0006-2952(90)90195-q.
The effects of hexachlorobenzene (HCB) administration on the development of porphyria and on changes in thyroid function and thyroid hormone metabolism were examined. Female Wistar rats were treated with HCB for 1 or 8 weeks. At both treatment times liver weight was notably increased with a slight change in thyroid weight at 8 weeks. Serum thyroxine (T4) levels were depressed, whereas levels of triiodothyronine (T3) were not depressed significantly at both treatment times. One or eight weeks of HCB treatment did not alter the incorporation and distribution of [125I] into intrathyroidal aminoacids. A 50% reduction in protein bound iodine (PB[125I]) was seen in both groups of animals. HCB altered [125I]T4 metabolism in rat liver slices, increasing T4 dehalogenation. HCB administration for 1 week did not affect urinary excretion of porphyrins or their precursors, or hepatic porphyrin content. The activity of aminolaevulinate synthase was not affected, but there was a 25% and 51% inhibition in porphyrinogen carboxy-lyase (PCL) activity for the uroporphyrinogen disappearance or the coproporphyrinogen formation respectively. After 8 weeks of HCB administration the rats showed a characteristic porphyria. Our results show that HCB treatment increased hepatic thyroxine metabolism, without alterations in thyroid hormone synthesis. Serum T4 and PCL activity behaved differently in both time- and dose-dependent studies, with serum T4 being the more sensitive parameter which responded at earlier times and lower doses.
研究了六氯苯（HCB）给药对卟啉症发展以及甲状腺功能和甲状腺激素代谢变化的影响。对雌性Wistar大鼠进行1周或8周的HCB处理。在两个处理时间点，肝脏重量均显著增加，8周时甲状腺重量有轻微变化。血清甲状腺素（T4）水平降低，而三碘甲状腺原氨酸（T3）水平在两个处理时间点均未显著降低。HCB处理1周或8周均未改变[125I]在甲状腺内氨基酸中的掺入和分布。两组动物的蛋白结合碘（PB[125I]）均降低了50%。HCB改变了大鼠肝切片中[125I]T4的代谢，增加了T4的脱卤作用。HCB给药1周不影响卟啉及其前体的尿排泄或肝脏卟啉含量。氨基乙酰丙酸合酶的活性未受影响，但尿卟啉原消失或粪卟啉原形成时，尿卟啉原羧基裂解酶（PCL）活性分别受到25%和51%的抑制。HCB给药8周后，大鼠出现典型的卟啉症。我们的结果表明，HCB处理增加了肝脏甲状腺素代谢，而甲状腺激素合成未发生改变。在时间和剂量依赖性研究中，血清T4和PCL活性表现不同，血清T4是更敏感的参数，在更早的时间和更低的剂量下就会有反应。
