Searching for novel biomarkers to diagnose drug-induced respiratory depression

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K18982
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 58040:Forensics medicine-related
• Research Institution: Kumamoto University
• Principal Investigator: Tsutsumi Hiroshi 熊本大学, 大学院生命科学研究部(医), 助教 (50849114)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 法医学 / 法中毒 / GABAA作動薬 / バイオマーカー

Outline of Final Research Achievements

The determination of the presence and degree of intoxication from drug overdose is crucial for the elucidation of incidents or accidents. Frequently detected in such cases are GABA_A receptor agonists, a class of sedative-hypnotic drugs, suggesting that objective measures beyond drug concentration could be highly useful in intoxication assessment.
In the quest for novel intoxication markers, we identified glycolytic metabolites, namely 2,3-Bisphosphoglycerate, Dihydroxyacetone-phosphate, Glycerol-3-phosphate, and Sedoheptulose-7-phosphate, as potential indicators. It was found that their levels could decrease upon administration of the GABA_A receptor agonist, diazepam. Furthermore, an increase in the expression of GAPDH, an enzyme in the glycolytic pathway, was also observed.

Free Research Field

法中毒

Academic Significance and Societal Importance of the Research Achievements

メタボロミクスおよび生化学的な実験により、GABAA作動薬をアストロサイト細胞株に投与すると解糖系に変化が生じることが見出された。この研究成果は、過量服薬による中毒の推定において新たな手がかりを提供し、法医学の発展に寄与することが期待される。解糖系とGABA作動薬との関連性を明らかにすることで、中毒推定の客観的指標を構築する新たな道が開かれるであろう。