Study of 4-hydroxybutyric acid produced after death

死后产生的4-羟基丁酸的研究

• 批准号: 15590594
• 负责人: SAKURADA Koichi
• 金额: $ 1.6万
• 依托单位: National Research Institute of Police Science
• 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-15590594/
• 关键词: GHB; BHB; citric acid; GABA; postmortem liver

γ-Hydroxybutyric acid(GHB) can be detected in the blood, urine, and liver of deceased persons who did not take the drug while alive. In order to clarify the pathway of GHB production after death, the amount of GHB produced in mouse liver after death was compared with that of β-hydroxybutyric acid(BHB). GHB significantly increased with time until 7 days after death (<0.1μg/g at day 0,1.0±0.9 μg/g at day 1,4.6±0.7 μg/g at day 3,and 45.3±21.0 μg/g at day 7). BHB significantly decreased at day 1 after death (2.3±1.3 μg/g at day 0,0.9±0.7 μg/g at day 1), and subsequently showed small increases until day 7(2.0±0.6 μg/g at day 3,5.4±1.8 μg/g at day 7). These results indicate that the mechanism of GHB production is different from that of BHB after death. Next, the effects of pretreatment of various chemical compounds on GHB and BHB concentrations in in vivo mouse liver at 24 h after death was examined. Citric acid was found to most significantly increase GHB concentrations (34.4±23.9 μg/g), and additional ampicillin significantly suppressed the increase by approximately 74% in in vitro mouse liver. This result indicates that GHB may arise from citric acid, with levels increasing with bacteria-induced citric acid fermentation after death. On the other hand, although no compounds significantly increased BHB concentrations at 24 h after death, high concentrations of BHB (139.4±113.7 μg/g, control) were detected at 0 h after death. This result supports a known theory that keto acids such as BHB are synthesized in the liver when the TCA cycle is disrupted due to starvation.The present results indicate that citric acid, which produced via citric acid fermentation, might be the main precursor of GHB produced in the liver after death, and the pathway of GHB production after death is clearly different from that of BHB.

生前未服用该药物的死者的血液、尿液和肝脏中可检测到γ-羟基丁酸（GHB）。为了明确死后GHB的产生途径，将小鼠死后肝脏中GHB的产生量与β-羟基丁酸(BHB)的产生量进行了比较。 GHB随时间显着增加，直至死后7天（第0天<0.1μg/g，第1天1.0±0.9μg/g，第3天4.6±0.7μg/g，第7天45.3±21.0μg/g）。 BHB在死后第1天显着下降（第0天为2.3±1.3μg/g，第1天为0.9±0.7μg/g），随后直到第7天出现小幅增加（第3天为2.0±0.6μg/g，第7天为5.4±1.8μg/g）。这些结果表明GHB产生的机制与死后BHB的产生机制不同。接下来，检查了各种化合物预处理对死后24小时体内小鼠肝脏中GHB和BHB浓度的影响。研究发现柠檬酸最能显着增加 GHB 浓度 (34.4±23.9 μg/g)，而额外的氨苄青霉素可显着抑制体外小鼠肝脏中约 74% 的增加。这一结果表明GHB可能来自柠檬酸，其水平随着细菌死亡后诱导的柠檬酸发酵而增加。另一方面，虽然没有化合物显着增加死后24小时的BHB浓度，但在死后0小时检测到高浓度的BHB（139.4±113.7μg/g，对照）。这一结果支持了一个已知的理论，即当 TCA 循环因饥饿而中断时，肝脏中会合成 BHB 等酮酸。目前的结果表明，通过柠檬酸发酵产生的柠檬酸可能是死后肝脏中产生 GHB 的主要前体，并且死后 GHB 产生的途径与 BHB 明显不同。