Uptake, tissue distribution, and excretion of brevetoxin 3 administered to rats by intratracheal instillation
Uptake, tissue distribution, and excretion of brevetoxin 3 administered to rats by intratracheal instillation
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DOI：
10.1080/009841099157656
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发表时间：
1999-07-09
期刊：
影响因子：
--
通讯作者：
Baden, DG
中科院分区：
文献类型：
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作者：
Benson, JM;Tischler, DL;Baden, DG
Brevetoxins是由海洋甲藻Ptychodiscus brevis产生的环状聚醚神经毒素。赤潮对鱼类、海洋哺乳动物和人类有毒。人类暴露于含有短毒素的海喷雾气雾剂可能会出现呼吸道刺激。由于人类暴露于短尾寒毒的主要途径是通过呼吸道，因此本研究的目的是检查通过气管内滴注给予肺的短尾寒毒3（PbTx-3）的毒代动力学。21只雄性F344/CrI BR大鼠，12周龄，通过腹膜内滴注给予H-3-PbTx-3（1 μ Ci，6.6 μ g PbTx-3/kg）。在暴露后0.5、3、6、24、48和96 h处死每组3只大鼠，并收集组织。将另外3只大鼠置于玻璃代谢笼中，收集7天内的尿液和粪便。PbTx-3相关的活动被迅速从肺中清除，并分布在整个身体，主要是尸体，肠和肝脏。血液、脑和脂肪占给药剂量的百分比最低。尽管大部分PbTx-3从肺、肝脏和肾脏中迅速清除，但每个器官中存在的初始浓度的约20%仍保留了7天。脑和脂肪中PbTx-3的浓度较低，但随着时间的推移保持相对恒定。粪便中排泄的PbTx-3相关活性约为尿液中的两倍，大部分排泄发生在滴注后48小时内。这项研究的结果表明，超过80%的PbTx-3从肺迅速吸收到血液中，并分布到所有组织中。含有最大量的PbTx-3相关活性的组织反映了化合物的沉积部位、储存室以及代谢和排泄的主要途径。这些结果表明，呼吸途径暴露于短吻蝮蛇毒导致短吻蝮蛇毒的全身分布，并表明初始呼吸刺激和支气管收缩可能只是与短吻蝮蛇毒吸入相关的总体毒理学后果的一部分。
Brevetoxins are cyclic polyether neurotoxins produced by the marine dinoflagellate Ptychodiscus brevis. Blooms of P. brevis (red tides) are toxic to fish, marine mammals, and humans. Humans exposed to seaspray aerosols containing brevetoxins may experience respiratory tract irritation. Because a major route of human exposure to brevetoxins is via the respiratory trace, the objective of this study was to examine the toxicokinetics of brevetoxin 3 (PbTx-3) administered to the lung by intratracheal instillation. Twenty-one male F344/CrI BR rats, 12 wk of age, were administered H-3-PbTx-3 (1 mu Ci, 6.6 mu g PbTx-3/kg) by intratracheal instillation. Groups of 3 rats were sacrificed at 0.5, 3, 6, 24, 48, and 96 h after exposure, and tissues were collected. Three additional rats were placed in glass metabolism cages for collection of urine and feces over a 7-d period. PbTx-3-associated activity was cleared rapidly from the lung and distributed throughout the body, chiefly to the carcass, intestines, and liver. Blood, brain, and fat contained the lowest percentages of the administered dose. Although a majority of the PbTx-3 was cleared rapidly from lung, liver, and kidneys, approximately 20% of the initial concentration present in each organ was retained for 7 d. Concentrations of PbTx-3 in brain and fat were low, but remained relatively constant over time. Approximately twice as much PbTx-3-associated activity was excreted in feces than in urine, with the majority of excretion occurring within 48 h after instillation. The results of this study indicate that over 80% of the PbTx-3 is rapidly absorbed from the lung to the blood and distributed to all tissues. The tissues containing the greatest amount of PbTx-3-associated activity reflect the compound's site of deposition, storage compartment, and major route of metabolism and excretion. These results illustrate that brevetoxin exposure by the respiratory route results in systemic distribution of brevetoxin and suggest that the initial respiratory irritation and bronchoconstriction may only be a part of the overall toxicological consequences associated with brevetoxin inhalation.