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改良 Irwin 试验检测 Sprague-Dawley 大鼠中 BMEDA 的神经行为。

Neurobehavioral assessment of BMEDA by modified Irwin test in Sprague-Dawley rats.

机构信息

Department of Isotope Application Research, National Atomic Research Institute, 1000 Wenhua Road, Jiaan Village, Longtan District, Taoyuan, 325, Taiwan, ROC.

Department of Isotope Application Research, National Atomic Research Institute, 1000 Wenhua Road, Jiaan Village, Longtan District, Taoyuan, 325, Taiwan, ROC.

出版信息

Regul Toxicol Pharmacol. 2024 Nov;153:105703. doi: 10.1016/j.yrtph.2024.105703. Epub 2024 Sep 17.

DOI:10.1016/j.yrtph.2024.105703
PMID:39299678
Abstract

The neurobehavioral assessment of N,N-bis(2-mercapatoethly)-N',N'-diethylenediamine (BMEDA), which can form a chelate with rhenium-188 (Re) to produce the Re-BMEDA-liposome, was evaluated. The purpose of this study was to evaluate the potential neurobehavioral changes by using the functional observational battery observation procedures when intravenous injection of BMEDA to Sprague-Dawley rats. Rats were administered BMEDA at dose levels of 1, 2, and 5 mg/kg. No mortalities were observed. There are some observations related to BMEDA treatment found in the 5 mg/kg dose group at 10 min post-dose. Tremor was observed in one male rat and seven female rats. The increased respiration, vocalization, not easy to handle and/or loss of tone in the limb were observed in both males and females, and increased body temperature was observed in male animals. Based on the results, a single intravenous dose of BMEDA administered to rats resulted in increased respiration, vocalization, not easy to handle and/or loss of tone in the limb increasing at the dose level of 5 mg/kg. No neurobehavioral effects were noted after BMEDA administration up to the dose level of 2 mg/kg. The information of this study will provides a point of reference to design appropriately therapeutic studies for future human use.

摘要

对 N,N-双(2-巯基乙硫基)-N',N'-二乙撑二胺(BMEDA)的神经行为评估,BMEDA 可与铼-188(Re)形成螯合物,从而产生 Re-BMEDA-脂质体。本研究的目的是通过静脉注射 BMEDA 到 Sprague-Dawley 大鼠时使用功能观察电池观察程序来评估潜在的神经行为变化。大鼠以 1、2 和 5mg/kg 的剂量水平给予 BMEDA。未观察到死亡。在 5mg/kg 剂量组的 10 分钟后观察到与 BMEDA 治疗有关的一些观察结果。一只雄性大鼠和七只雌性大鼠出现震颤。在雄性和雌性大鼠中观察到呼吸增加、发声、肢体难以处理和/或失去张力,雄性动物的体温升高。基于这些结果,单次静脉注射 BMEDA 导致 5mg/kg 剂量水平的呼吸增加、发声、肢体难以处理和/或失去张力。在 2mg/kg 剂量水平以下,BMEDA 给药后未观察到神经行为效应。本研究的信息将为未来人类使用提供设计适当治疗研究的参考点。

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