National Oceanographic and Atmospheric Administration, Center for Coastal Environmental Health and Biomolecular Research, Charleston, SC 29412, USA.
Toxicology. 2012 Mar 29;294(1):36-41. doi: 10.1016/j.tox.2012.01.012. Epub 2012 Jan 28.
Domoic acid (DA) is a potent neurotoxin that has both marine wildlife and human health impacts, including developmental effects during prenatal exposure in rodent models. However, little is known regarding DA toxicokinetics in the fetal unit during maternal-fetal transfer. Tissue distribution and toxicokinetics of DA were investigated in pregnant rats and their pups just prior to birth at gestational day 20. Pregnant Sprague Dawley rats were given an intravenous dose of 1.0 mg DA/kg and samples of maternal plasma, fetal plasma, placenta, amniotic fluid and fetal brain were taken at intervals over 24 h. Toxicokinetic parameters were determined using WinNonLin software analysis. Maternal plasma DA log concentration-time curves fit a two compartment pharmacokinetic profile, with alpha and beta half-lives of elimination of 26.9 and 297 min, respectively. Placenta had a C(max) of 752 ng/mL and a terminal half-life of 577 min. Maternal-fetal transfer between the plasma compartments was 31% with a fetal plasma C(max) of 86 ng/mL at 60 min and terminal half-life of 553 min. Amniotic fluid and fetal brain had overall averages of 27±12 ng/mL and 8.12 ng/g, respectively, and did not show evidence of elimination over 24 h. The longer fetal retention of DA, particularly in amniotic fluid, indicates that the fetus may be continually re-exposed during gestation, which could potentially lead to a disease state even at small exposure dose. This has implications for the California sea lions (Zalophus californianus), which exhibit an epilepsy-like disease that arises months after DA producing blooms.
软骨藻酸（DA）是一种强效神经毒素，对海洋野生动物和人类健康都有影响，包括在啮齿动物模型的产前暴露期间的发育影响。然而，对于母体-胎儿转移过程中胎儿单位的 DA 毒代动力学知之甚少。在妊娠第 20 天，研究人员在即将分娩时研究了怀孕大鼠及其幼崽的 DA 组织分布和毒代动力学。怀孕的 Sprague Dawley 大鼠静脉注射 1.0mg DA/kg，在 24 小时内的不同时间点采集母血浆、胎儿血浆、胎盘、羊水和胎儿大脑样本。使用 WinNonLin 软件分析确定毒代动力学参数。母体血浆 DA 对数浓度-时间曲线符合二室药代动力学模型，消除的 alpha 和 beta 半衰期分别为 26.9 和 297 分钟。胎盘的 C(max)为 752ng/mL，终末半衰期为 577 分钟。血浆隔室之间的母体-胎儿转移率为 31%，胎儿血浆 C(max)为 86ng/mL，在 60 分钟时达到，终末半衰期为 553 分钟。羊水和胎儿大脑的平均浓度分别为 27±12ng/mL 和 8.12ng/g，在 24 小时内没有消除的证据。DA 在胎儿中的滞留时间较长，特别是在羊水中，表明胎儿在妊娠期间可能会持续重新暴露，即使在小剂量暴露的情况下也可能导致疾病状态。这对加利福尼亚海狮（Zalophus californianus）有影响，海狮会出现类似癫痫的疾病，在软骨藻酸产生水华后数月出现。
