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.

可以在没有生命时未服用该药物的死者的血液，尿液和肝脏中检测到γ-羟基丁酸（GHB）。为了阐明死亡后GHB产生的途径，将死亡后小鼠肝脏中产生的GHB量与β-羟基丁酸（BHB）的GHB量进行了比较。 GHB随时间显着增加，直到死后7天（第3天，第1，1,4.6±0.7μg/g的第0,1.0±0.9μg/g，在第7天为45.3±21.0μg/g）。死亡后第1天的BHB显着降低（第1天为2.3±1.3μg/g，在第1天，第0、0.9±0.7μg/g），随后显示出较小的增加，直到第7天（2.0±0.6μg/g）在第7天，第3,5.4±1.8μg/g时，第7天）。这些结果表明，GHB产生的机理与死亡后BHB的机制不同。接下来，检查了各种化合物对死亡后24小时内体内小鼠肝脏GHB和BHB浓度的预处理的影响。发现柠檬酸最大程度地增加了GHB浓度（34.4±23.9μg/g），并且额外的氨木蛋白在体外小鼠肝脏中显着抑制了大约74％的增加。该结果表明GHB可能是由柠檬酸引起的，随着细菌诱导的柠檬酸发酵的水平增加。另一方面，尽管在死亡后24小时内没有明显增加BHB浓度，但在死亡后0小时检测到高浓度的BHB（139.4±113.7μg/g，对照）。该结果支持了一种已知的理论，即当TCA周期因饥饿而破坏时，在肝脏中合成了酮酸。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在肝脏中产生的GHB的主要先兆，显然与GHB死后的途径不同于BHB。