2004 Fiscal Year Final Research Report Summary
Forensic toxicology of drug - induced acute cardiac death based on an acuto chloroquine poisoning model -
| Project/Area Number |
15590579
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Legal medicine
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| Research Institution | Kumamoto University |
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Principal Investigator |
YONEMITSU Kosei Kumamoto University, Graduate School of Medical Sciences, Department of Forensic Medicine, Lecturer, 大学院・医学薬学研究部, 講師 (10128332)
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| Co-Investigator(Kenkyū-buntansha) |
TSUNENARI Shigeyuki Kumamoto University, Graduate School of Medical Sciences, Department of Forensic Medicine, Professor, 大学院・医学薬学研究部, 教授 (80040202)
KOREEDA Ako Kumamoto University, Graduate School of Medical Sciences, Department of Forensic Medicine, Assistant lecturer, 大学院・医学薬学研究部, 助手 (80284751)
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| Project Period (FY) |
2003 – 2004
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| Keywords | chloroquine / acute drug poisoning / cardiac sudden death / immunohistochemistry / electrocardiogram / Purkinje'sfiber / QT prolongation |
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| Research Abstract |
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 Tanzania
HPLC 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 mice
Immuno-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 pig
Intravenous 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
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