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Morphological changes of endothelial cells and pharmaceutical actions of drugs and poisons using the cells.

内皮细胞的形态变化以及利用细胞的药物和毒物的药作用。

基本信息

批准号：
14570383
负责人：
TAKAYASU Tatsunori
金额：
$ 2.24万
依托单位：
KANAZAWA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570383/
关键词：
Drugs and poisons Assessment of toxicity Endothelial cell Screening Morphological changes Cell level Acute intoxication Lethal dose 薬理作用サイトカインケモカインコカインフェノバルビタール

项目摘要

Toxicity of drugs and poisons shows as lethal dose in human. In this study, relationship between the lethal dose and dose of the cell death was examined using human endothelial cells(HUVEC). Death of HUVEC judged with morphological changes in culture fluids mixed with drugs and poisons. Doses of the cell death using methamphetamine(MA), cocaine, phenobarbital(PB), paraquat(PQ) showed 5,5,5 and 0.1 mM, respectively. The other 57 drugs and poisons were screened with the same method. The most poisonous substance was arsenite sodium (0.01mM) and the least poisonous one was methanol(2M). By the references, lethal doses of human(including presumption values) in MA, cocaine, PB and PQ were 1.3-20,7-10,14-200 and 14-40mg/kg, respectively. To compare the values between lethal dose and dose of cell death, the unit made mg/L of mg/kg. The concentrations of MA, cocaine, PB and PQ were 0.007-0.1,0.002-0.003,0.06-0.9 and 0.05-0.16mM, respectively. In MA, cocaine and PB lethal doses of human showed 1/6 to 1/700 comparing to cell death of HUVEC. In PQ, however, the dose of human was same level as cell death of HUVEC. In the same manner, 49 substances were plotted between lethal dose of human and the cell death of HUVEC. When the relation line was made, the correlation coefficient(r) was 0.310, indicating poor relationship. In conclusion, morphological changes of HUVEC showed poor relationship to lethal dose of human in total 61 drugs and poisons examined. Further examination needs to determine the relationship between lethal dose and endothelial cell death in human.

药物和毒物的毒性表现为对人体的致死量。在这项研究中，使用人内皮细胞（HUVEC）检查致死剂量和细胞死亡剂量之间的关系。HUVEC在药物和毒物混合培养液中的死亡通过形态学变化判断。甲基苯丙胺（MA）、可卡因、苯巴比妥（PB）、百草枯（PQ）的细胞死亡剂量分别为5，5，5和0.1mM。其余57种药物和毒物用同样的方法进行筛选。毒性最强的是亚砷酸钠（0.01mM），毒性最弱的是甲醇（2 M）。参考文献，MA、可卡因、PB和PQ对人体的致死剂量（包括推测值）分别为1.3- 20、7 - 10、14 -200和14- 40 mg/kg。为了比较致死剂量和细胞死亡剂量之间的值，单位为mg/kg的mg/L。MA、可卡因、PB和PQ的浓度分别为0.007- 0.1、0.002 - 0.003、0.06 -0.9和0.05-0.16mM。在MA中，可卡因和PB对人的致死剂量为HUVEC细胞死亡的1/6至1/700。而PQ中，人的剂量与HUVEC的细胞死亡水平相同。以同样的方式，49种物质在人的致死剂量和HUVEC的细胞死亡之间作图。当绘制相关线时，相关系数（r）为0.310，表明相关性较差。总之，在所检测的61种药物和毒物中，HUVEC的形态学变化与人体的致死剂量关系不大。致死剂量与内皮细胞死亡的关系有待进一步研究。