Analysis of drug toxicity mechanism and toxicity evaluation method using targeted metabolome method

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09202
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Legal medicine
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Funakoshi Takeshi 東京医科歯科大学, 大学院医歯学総合研究科, 助教 (40444715)
• Co-Investigator(Kenkyū-buntansha): 上村 公一 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (30244586) ; 秋 利彦 東京医科歯科大学, 大学院医歯学総合研究科, 准教授 (60304474)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: メタボローム解析 / 細胞毒性

Outline of Final Research Achievements

In this study, we use the latest targeted metabolomics method to identify drug-dependent signal pathways, and quantify the increase or decrease of metabolites that fluctuate with these drugs, and compare the toxicity between drugs. Finally, we aimed to establish a new toxicity evaluation method for drugs that are unknown toxicity.
From metabolome analysis, in neurons exposed to norephedrine which is stimulant drug, significant changes in metabolites related to energy metabolism, amino acid metabolism and lipid metabolism were observed. These results are consistent with lipid metabolism abnormalities, generation of reactive oxygen species and decrease in ATP, which have been clarified in past studied. Therefore, it is suggested that the metabolome analysis method constructed in this study is very useful in examining the toxic mechanism due to the toxic substance.

Free Research Field

細胞中毒学

Academic Significance and Societal Importance of the Research Achievements

薬毒物による毒性機序の解明と毒性評価は法医実務上重要であるが、数多存在する薬毒物の内その毒性機序の詳細が明らかな物は少なく、危険ドラッグなど毒性が不明な薬物も多く存在するため、薬物の毒性および機序をより簡便に検討する手法の確立が求められている。本研究で行ったターゲットメタボロミクスの手法は、従来の方法に比べより簡便かつ短期間で薬物毒性および機序を検討することが可能となることから、今後法医実務においても非常に有用となることが期待される。