|Budget Amount *help
¥2,500,000 (Direct Cost : ¥2,500,000)
Fiscal Year 2004 : ¥1,000,000 (Direct Cost : ¥1,000,000)
Fiscal Year 2003 : ¥1,500,000 (Direct Cost : ¥1,500,000)
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.