Davidson M D, Fujimoto J M
Toxicol Appl Pharmacol. 1987 Jan;87(1):57-66. doi: 10.1016/0041-008x(87)90084-6.
Male Sprague-Dawley rats were treated ip on Day 0 with 0, 20, 50, or 100 micrograms/kg of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and biliary tree permeability was evaluated on Days 2, 4, 7, 10, 14, or 20 by segmented retrograde intrabiliary injection of [3H]sucrose or [14C]mannitol. Seven days after 100 micrograms/kg TCDD, the percentage recovery in bile of both [3H]sucrose (73.9 +/- 4.2 vs 27.6 +/- 7.6, control vs TCDD, means +/- SE) and [14C]mannitol (22.7 +/- 2.2 vs 12.1 +/- 2.2) was decreased, demonstrating that the permeabilities of both the intracellular (canalicular) and paracellular pathways were increased. Seven days after 50 micrograms/kg TCDD, the recovery of [3H]sucrose was decreased (73.5 +/- 5.4 vs 39.0 +/- 2.8) but the recovery of [14C]mannitol was not (25.5 +/- 1.5 vs 22.9 +/- 1.9). Thus, an increase in paracellular permeability is obtained at a lower dose of TCDD. In rats treated with 100 micrograms/kg TCDD on Day 0, co-treatment with chlordecone (15 mg/kg/day on Days 2-6) or thyroxine (50 micrograms/kg on Day 2) had no effect. Pregnenolone-16 alpha-carbonitrile (75 mg/kg/day on Days 4-6) treatment increased [14C]mannitol recovery in both TCDD and control groups; its effect must not be specific. Methimazole given in drinking water (0.5%) on Days -7 through 7 reversed the increased permeability effects of TCDD (100 micrograms/kg) without affecting the biliary tree permeability ([14C]mannitol recovery) of control animals.
在第0天，给雄性Sprague-Dawley大鼠腹腔注射0、20、50或100微克/千克的2,3,7,8-四氯二苯并对二恶英（TCDD），并在第2、4、7、10、14或20天通过分段逆行胆管内注射[3H]蔗糖或[14C]甘露醇来评估胆管树的通透性。在给予100微克/千克TCDD七天后，[3H]蔗糖（对照组与TCDD组分别为73.9±4.2与27.6±7.6，均值±标准误）和[14C]甘露醇（22.7±2.2与12.1±2.2）在胆汁中的回收率均降低，表明细胞内（胆小管）和细胞旁途径的通透性均增加。在给予50微克/千克TCDD七天后，[3H]蔗糖的回收率降低（73.5±5.4与39.0±2.8），但[14C]甘露醇的回收率未降低（25.5±1.5与22.9±1.9）。因此，在较低剂量的TCDD下即可实现细胞旁通透性的增加。在第0天给予100微克/千克TCDD的大鼠中，与十氯酮（在第2 - 6天为15毫克/千克/天）或甲状腺素（在第2天为50微克/千克）共同处理没有效果。孕烯醇酮-16α-腈（在第4 - 6天为75毫克/千克/天）处理增加了TCDD组和对照组中[14C]甘露醇的回收率；其作用并非特异性的。在第-7天至第7天通过饮用水给予甲巯咪唑（0.5%）可逆转TCDD（100微克/千克）增加的通透性作用，而不影响对照动物的胆管树通透性（[14C]甘露醇回收率）。
