Biliary elimination of oral 2,4-dichlorophenoxyacetic acid and its metabolites in male and female Sprague-Dawley rats, B6C3F1 mice, and Syrian hamsters.

R J Griffin, J Salemme, J Clark, P Myers, L T Burka
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引用次数: 7

Abstract

The role of biliary elimination in the metabolic disposition of 2,4-D was evaluated in male and female Sprague-Dawley rats, B6C3F1 mice, and Syrian hamsters. Following cannulation of the bile duct, an intragastric (ig) dose of 2,4-D (200 mg/kg) was administered and bile was collected at 30- or 60-min intervals for up to 6 h. Bile flow rates were constant in rats, increased in mice, and decreased in hamsters throughout the collection periods. Total recovery of radioactivity was greatest in male mice (about 7% of administered dose over 4 h). Female mice and rats of both sexes excreted about 3% over the same interval and male and female hamsters about 1%. About 71-88% of the activity in bile was parent compound. The glycine conjugate of 2,4-D was found in bile from mice, rats, and hamsters and the taurine conjugate in bile from mice. The only sex-dependent difference in the metabolite profile was in mice. Male mice excreted twice as much glycine conjugate as female mice. An additional minor metabolite (4-7%) was present in rat and mouse bile. This was tentatively identified as 2,4-D-glucuronide based on its hydrolysis by beta-glucuronidase. One more very minor metabolite (3%) was detected in rat bile but was not characterized due to its lability. The results of this study indicate that there are species-dependent differences in the biliary elimination of 2,4-D but not sex-dependent differences.

雄性和雌性Sprague-Dawley大鼠、B6C3F1小鼠和叙利亚仓鼠口服2,4-二氯苯氧乙酸及其代谢物的胆道消除
在雄性和雌性Sprague-Dawley大鼠、B6C3F1小鼠和叙利亚仓鼠中评估了胆道消除在2,4- d代谢处置中的作用。在胆管插管后,给予大剂量2,4- d (200 mg/kg)灌胃,每隔30或60分钟收集胆汁,持续6小时。在整个收集期间,大鼠的胆汁流率保持不变,小鼠的胆汁流率增加,仓鼠的胆汁流率下降。在4小时内,雄性小鼠的放射性总回收率最高(约为给药剂量的7%)。雌性小鼠和大鼠在相同时间内的排泄率约为3%,雌雄仓鼠的排泄率约为1%。胆汁中约有71-88%的活性为母体化合物。在小鼠、大鼠和仓鼠的胆汁中发现了2,4- d的甘氨酸缀合物,在小鼠胆汁中发现了牛磺酸缀合物。代谢物谱中唯一的性别依赖性差异是在小鼠中。雄性小鼠分泌的甘氨酸偶联物是雌性小鼠的两倍。在大鼠和小鼠的胆汁中存在另一种次要代谢物(4-7%)。经β -葡萄糖醛酸酶水解初步鉴定为2,4- d -葡萄糖醛酸。在大鼠胆汁中检测到另一种非常微小的代谢物(3%),但由于其不稳定而未被表征。本研究结果表明,2,4- d的胆道清除存在种属差异,但不存在性别差异。
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