Benson Janet M, Gomez Andrea P, Statom Gloria L, Tibbetts Brad M, Fleming Lora E, Backer Lorraine C, Reich Andrew, Baden Daniel G
Lovelace Respiratory Research Institute, 2425 Ridgecrest Dr. SE., Albuquerque NM 87108, USA.
Toxicon. 2006 Dec 15;48(8):1018-26. doi: 10.1016/j.toxicon.2006.08.008. Epub 2006 Aug 18.
The purpose of this study was to examine the distribution of brevetoxin-3 administered to pregnant dams and to determine the extent of placental transport to fetuses. Twenty-nine pregnant CD-1 mice were administered (3)H-brevetoxin-3 ( approximately 1.3 microCi/animal; approximately 2.8 microg compound/kg) by intratracheal instillation on one of gestational days 15-18. Groups of four or five dams were killed at selected times through 48 h post-dosing. Four pregnant dams were administered (3)H-brevetoxin-3 on gestational day 15 or 16 via osmotic minipump to provide continuous delivery of compound ( approximately 0.13 microCi, 7.5 ng compound/day) over a 72-h period. Then the dams and fetuses were killed. Brevetoxin-associated radioactivity was detected in placentas and fetuses within 0.5h of intratracheal administration. Concentrations of brevetoxin equivalents in fetuses were approximately 0.3 ng/g throughout the 48-h post-dosing, resulting in a calculated dose to fetuses of 19 ng/gh. Following brevetoxin infusion, concentration of brevetoxin equivalents in fetuses was 0.1 ng/g, lower than that present in most maternal tissues. Results demonstrated placental transport of brevetoxin or its metabolites following maternal acute exposure and repeated low-dose exposure. The consequences of these findings for pregnant women exposed to brevetoxins by inhalation or ingestion remain to be determined.
本研究的目的是检测给予怀孕母鼠的短裸甲藻毒素-3的分布情况,并确定其通过胎盘转运至胎儿的程度。29只怀孕的CD-1小鼠在妊娠第15 - 18天的某一天通过气管内滴注给予(3)H-短裸甲藻毒素-3(约1.3微居里/只动物;约2.8微克化合物/千克)。在给药后48小时内的选定时间处死四五只母鼠为一组。4只怀孕母鼠在妊娠第15天或16天通过渗透微型泵给予(3)H-短裸甲藻毒素-3,以便在72小时内持续输送化合物(约0.13微居里,7.5纳克化合物/天)。然后处死母鼠和胎儿。气管内给药后0.5小时内在胎盘和胎儿中检测到与短裸甲藻毒素相关的放射性。在给药后的48小时内,胎儿中短裸甲藻毒素当量的浓度约为0.3纳克/克,计算得出胎儿的剂量为19纳克/克时。短裸甲藻毒素输注后,胎儿中短裸甲藻毒素当量的浓度为0.1纳克/克,低于大多数母体组织中的浓度。结果表明,母体急性暴露和反复低剂量暴露后,短裸甲藻毒素或其代谢产物可通过胎盘转运。这些发现对通过吸入或摄入接触短裸甲藻毒素的孕妇的影响尚待确定。