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急性给药后[14C]西维因在大鼠怀孕、未怀孕及胎儿组织中的排泄与分布

Excretion and disposition of [14C]carbaryl in pregnant, non-pregnant and foetal tissues of the rat after acute administration.

作者信息

Strother A, Wheeler L

出版信息

Xenobiotica. 1980 Feb;10(2):113-24. doi: 10.3109/00498258009033737.

Abstract
  1. Non-pregnant or pregnant Sprague-Dawley rats on the 18th and 19th days of gestation were injected i.p. with a tracter dose (2.8 microCi/kg) of either [ring-14C]carbaryl or [carbonyl-14C]carbaryl. Distribution of total 14C was examined in foetal, maternal and non-pregnant rat tissues. Pregnancy alters the disposition and excretion of carbaryl. 2. Carbaryl crossed the placenta and was rapidly distributed in all foetal tissues. Highest concentrations were seen in foetal kidney. At 8 h after injection, foetal brain, heart and lung all contained more 14C, on a weight basis, than their maternal organ counterparts. Elimination from the whole foetus was biphasic, and after 8 h approx. 3% of the dose was still present in the whole foetus. 3. Significantly more 14CO2 was exhaled by the pregnant rat during 8 h than by non-pregnant. Urinary excretion of 14C after dosage with [ring-14C]carbaryl was significantly less in pregnant than in non-pregnant rats. 4. Kinetically, the tissue distribution of 14C from carbaryl or metabolites was biphasic in pregnant and non-pregnant animals. [14C]carbaryl concn. declined rapidly for 1 to 2 h. After 2 h the 14C levels from animals dosed with [ring-14C]carbaryl declined more slowly. 5. The pattern of 14C distribution was more complicated after injection of [carbonyl-14C]carbaryl. The 14C activity increased in the animal tissues after 2 h, in contrast to animals dosed with [ring-14C]carbaryl. Non-pregnant animals treated with [carbonyl-14C]carbaryl did not show a similar pattern of distribution. Carbamylated tissue proteins may, after time, release some bound carbonyl-14C label, causing the increase in 14C activity seen between 2 and 8 h. However, this does not necessarily imply uptake of the intact carbamate.
摘要
  1. 在妊娠第18天和第19天的未孕或孕龄Sprague-Dawley大鼠经腹腔注射给予示踪剂量(2.8微居里/千克)的[环-14C]西维因或[羰基-14C]西维因。检测了胎儿、母体和未孕大鼠组织中总14C的分布情况。妊娠会改变西维因的处置和排泄。2. 西维因穿过胎盘并迅速分布于所有胎儿组织中。胎儿肾脏中的浓度最高。注射后8小时,按重量计算,胎儿脑、心脏和肺中的14C含量均高于其母体相应器官。整个胎儿体内的消除呈双相性,8小时后,整个胎儿体内仍约有3%的剂量。3. 妊娠大鼠在8小时内呼出的14CO2明显多于未孕大鼠。给予[环-14C]西维因后,妊娠大鼠的14C尿排泄量明显低于未孕大鼠。4. 从动力学角度看,西维因或其代谢产物的14C在妊娠和未孕动物的组织分布呈双相性。[14C]西维因浓度在1至2小时内迅速下降。2小时后,给予[环-14C]西维因的动物体内14C水平下降得更慢。5. 注射[羰基-14C]西维因后,14C的分布模式更为复杂。与给予[环-14C]西维因的动物相比,2小时后动物组织中的14C活性增加。用[羰基-14C]西维因处理的未孕动物未表现出类似的分布模式。随着时间的推移,氨基甲酰化的组织蛋白可能会释放一些结合的羰基-14C标记,导致在2至8小时内观察到14C活性增加。然而,这不一定意味着完整氨基甲酸酯的摄取。

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