Forensic toxicology of drug - induced acute cardiac death based on an acuto chloroquine poisoning model -

基于急性氯喹中毒模型的药物引起的急性心源性死亡的法医毒理学-

• 批准号: 15590579
• 负责人: YONEMITSU Kosei
• 金额: $ 1.98万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590579/
• 关键词: chloroquine; acute drug poisoning; cardiac sudden death; immunohistochemistry; electrocardiogram; Purkinje'sfiber; QT prolongation; 免疫染角; Q-T間隔

Sudden deaths after chloroquine(CQ) ingestion might be produced by its cardiotoxicity, although the precise mechanism is not clear. This study was conducted to investigated the characters of drug induced cardiac sudden death by using human CQ poisoning cases as well as animal experiments.1.CQ poisoning cases in TanzaniaHPLC analysis of anti-malaria agent, CQ in blood and tissues was applied to three forensic autopsy cases in Dar es Salaam, Tanzania. CQ concentrations in femoral vein blood were 8.8,48.8 and 43.8 ug/ml in three cases respectively, which were high enough to attribute the cause of deaths to an acute CQ poisoning. There were great site dependent variations in blood CQ levels. The right heart blood samples were very high, which may be explained by incomplete distribution of the drug before death or postmortem diffusion from liver and its surrounding blood, as high tissue levels were remarkable in the liver and kidney. Histopathological studies of the heart revealed some infl … More ammatory and fibrotic changes in some cases. However, these were not characteristic findings to chloroquine.2.Production of anti-CQ polychloral antibodies and immuno-histochemistry of CQ in miceImmuno-histochemistry of CQ in mice tissues was performed by using anti-CQ polychlonal antibodies. CQ distributed in cardiac myocites and Purkinje's fiber, which might relate to its cardiotoxicity. Further experiments were needed to confirm it. In other tissues, positive area were remarkable in following area ; Brain : chorioid plexus and surrounding cerebral cortex, Lung : type II pneumocyte and macrophage, Liver : hepatocyte around central and periportal vein, Kidney : medulla, especially the epithelial cells of the distal convoluted tubule and collecting duct.3.ECG changes by administration of chloroquine in quinia pigIntravenous administration of 3,10 and 20mg/kg CQ dose-dependently prolonged QTc intervals in guinea pigs. The integrity of the effects was similar to those of quinidine, which is a typical QTc prolongation drug.4.Development of a simple CQ detection in liquid samples by using anti-CQ monoclonal antibodies.A simple semi-quantitative analysis of CQ using anti-CQ monoclonal antibodies were applied to spiked standard samples. The method successfully distinguished the three drug levels of fatal, toxic and therapeutic in the test samples. Less

氯喹(CQ)摄入后的猝死可能是由其心脏毒性引起的，尽管确切的机制尚不清楚。本研究利用人体CQ中毒病例和动物实验，对坦桑尼亚CQ中毒病例进行了研究。1.对坦桑尼亚达累斯萨拉姆3例法医尸检病例进行了抗疟疾药物、血液和组织中CQ的高效液相色谱分析。3例股静脉血CQ浓度分别为8.8、48.8和43.8ug/ml，均为急性CQ中毒死亡。血CQ水平有很大的部位依赖性变化。右心血样含量很高，这可能与生前药物分布不完全或死后从肝脏及其周围血液扩散有关，因为肝脏和肾脏组织中含量较高。心脏的组织病理学研究揭示了一些…在某些病例中有更多炎症性和纤维性改变。2.小鼠抗CQ多氯抗体的产生及CQ的免疫组织化学用抗CQ多克隆抗体对小鼠组织进行CQ免疫组织化学研究。CQ分布于心肌肌浆网和浦肯野纤维，可能与其心脏毒性有关。还需要进一步的实验来证实这一点。脑：绒毛膜神经丛及周围大脑皮质，肺：II型肺泡细胞和巨噬细胞，肝：门静脉周围肝细胞，肾脏：髓质，尤其是远端曲管和集合管的上皮细胞。3.豚鼠静脉注射氯喹3，10和20 mg/kg CQ可剂量依赖性延长QTC间期。利用抗CQ单抗建立了液体样品中CQ的简易检测方法，并对添加了CQ的标准样品进行了CQ的半定量分析。该方法成功地区分了测试样品中致死、毒性和治疗三种药物水平。较少

项目成果

HPLC analysis of anti-malaria agent, chloroquine in blood and tissue from forensic autopsy cases in Tanzania

• DOI: 10.1016/j.legalmed.2004.10.002
• 发表时间: 2005-03-05
• 期刊: Legal Medicine
• 影响因子: 1.5
• 作者: Yonemitsu, Kosei;Koreeda, Ako;Tsunenari, Shigeyuki
• 通讯作者: Tsunenari, Shigeyuki

HPLC analysis of anti-malaria agent, chloroquine in blood and tissues from forensic autopsy cases in Tanzania.

对坦桑尼亚法医尸检病例血液和组织中的抗疟疾药物氯喹进行 HPLC 分析。

• 发表时间: 2005
• 期刊: Legal Medicine 7(2)
• 作者: Kosei Yonemitsu;Ako Koreeda;Kazuhiko Kibayashi;Paul Ng'walali;Martin Mbonde;James Kitinya;Shigeyuki Tsunenari
• 通讯作者: Shigeyuki Tsunenari