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经口和腹腔内给予螺旋内酯后的药代动力学和毒理学数据。

Pharmacokinetic and toxicological data of spirolides after oral and intraperitoneal administration.

机构信息

Departamento de Farmacología, Facultad de Veterinaria, Universidad de Santiago de Compostela, 27002 Lugo, Spain.

出版信息

Food Chem Toxicol. 2012 Feb;50(2):232-7. doi: 10.1016/j.fct.2011.10.062. Epub 2011 Nov 11.

DOI:10.1016/j.fct.2011.10.062
PMID:22100396
Abstract

Spirolides are a kind of marine toxins included in the cyclic imine toxin group and produced by the dinoflagellate Alexandrium ostenfeldii. This study shows for the first time a complete and detailed description about the symptoms observed in mice when these toxins were intraperitoneal (i.p.) administered. It is also compared the i.p. toxicity of 13-desmethyl spirolide C (13-desMeC), 13,19-didesMeC (13,19-didesMeC) and 20-methyl spirolide G (20-Me-G) in experiments performed with highly purified toxins. The bioassay indicates that 13-desMeC and 13,19-didesMeC are extremely toxic compounds which have a LD(50) of 27.9μg/kg and 32.2μg/kg, respectively. However, when 20-MeG was i.p administrated with dose up 63.5μg/kg, no deaths were recorded. In order to evaluate the oral toxicity, spirolides were administered by gastric intubation into mice. Then, samples of blood, urine and faeces were collected and analyzed by liquid chromatography-mass spectrometry tandem (LC-MS/MS) technique. Spirolides appear in blood at 15min and in urine after 1h of being toxin administered. In summary, in this paper, it is provided new data about the toxicity, absorption, and excretion of spirolides in mouse. So far, little information is available on this item but necessary for spirolide regulation in the European Union (EU).

摘要

短沟藻毒素是一类海洋毒素,属于环亚胺毒素组,由菱形藻属中的亚历山大藻产生。本研究首次全面详细地描述了腹腔内(i.p.)给予这些毒素后小鼠观察到的症状。还比较了高纯度毒素实验中腹腔内(i.p.)毒性 13-去甲短沟藻毒素 C(13-desMeC)、13,19-二去甲短沟藻毒素 C(13,19-didesMeC)和 20-甲基短沟藻毒素 G(20-Me-G)的毒性。生物测定表明,13-desMeC 和 13,19-didesMeC 是极毒化合物,其 LD50 分别为 27.9μg/kg 和 32.2μg/kg。然而,当以 63.5μg/kg 的剂量腹腔内给予 20-Me-G 时,没有记录到死亡。为了评估口服毒性,将短沟藻毒素通过胃管给予小鼠。然后,采集血液、尿液和粪便样本,并通过液相色谱-串联质谱(LC-MS/MS)技术进行分析。短沟藻毒素在毒素给药后 15 分钟出现在血液中,1 小时后出现在尿液中。总之,本文提供了有关短沟藻毒素在小鼠体内的毒性、吸收和排泄的新数据。到目前为止,关于这一项目的信息很少,但对于欧盟(EU)对短沟藻毒素的监管是必要的。

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