A Detailed Analysis of Alcohol Pharmacokinetics in Healthy Korean Men / 대한법의학회지

To determine blood alcohol concentration (BAC) by extrapolation, an understanding of basal pharmacokinetics is indispensable. Breath alcohol concentration (BrAC) has been used for the determination of body alcohol concentration replaced by BAC in Korea. Therefore, the determination of BAC/BrAC ratio is a key problem in alcohol pharmacokinetics. Among several factors, the ingested dose of alcohol and the allelic variation of mitochondrial aldehyde dehydrogenase 2 (ALDH2) are the most significant factors influencing the pharmacokinetic parameters, particularly in the absorption and elimination phases. This study shows a detailed pharmacokinetic analysis of BAC and BrAC associated with genetic polymorphism including ALDH2 in 42 healthy Korean men. The change in the alcohol dose ingested influenced the maximum concentration (C(max)), the time to reach C(max) (T(max)), the absorption rate constant (K(01)), the area under the concentration-time curve (AUC(last)), and the hourly elimination rate. The conversion of wild-type 487Glu (ALDH2*1) to 487Lys (ALDH2*2) in human ALDH2 resulted in changes in C(max) (ALDH2*1/*1, 0.03+/-0.01 g/dL [+/-standard deviation] vs. ALDH2*1/*2, 0.05+/-0.004 g/dL [P<0.01]), AUC(last) (ALDH2*1/*1, 4.48+/-2.19 g.min/dL vs. ALDH2*1/*2, 7.52+/-1.26 g.min/dL [P<0.05]), and the BAC elimination rate (ALDH2*1/*1, 0.05+/-0.02 g/L/hr vs. ALDH2*1/*2, 0.09+/-0.01 g/L/hr [P<0.05]). Moreover, the comparison of BAC and BrAC by Bland-Altman plot showed good agreement, suggesting that the measurement of BrAC can be a good alternative for the determination of BAC, particularly in the post-absorption phase. These results provide fundamental information about the pharmacokinetics of alcohol and the determination of BAC in forensics.

Retraction: Ethanol Mediates Cell Cycle Arrest and Apoptosis in SK-N-SH Neuroblastoma Cells

This article has been retracted following a review by the Editorial Board.

Acetoaminophen-induced accumulation of 8-oxodeoxyguanosine through reduction of Ogg1 DNA repair enzyme in C6 glioma cells

Large doses of acetaminophen (APAP) could cause oxidative stress and tissue damage through production of reactive oxygen/nitrogen (ROS/RNS) species and quinone metabolites of APAP. Although ROS/RNS are known to modify DNA, the effect of APAP on DNA modifications has not been studied systematically. In this study, we investigate whether large doses of APAP can modify the nuclear DNA in C6 glioma cells used as a model system, because these cells contain cytochrome P450-related enzymes responsible for APAP metabolism and subsequent toxicity (Geng and Strobel, 1995). Our results revealed that APAP produced ROS and significantly elevated the 8-oxo- deoxyguanosine (8-oxodG) levels in the nucleus of C6 glioma cells in a time and concentration dependent manner. APAP significantly reduced the 8- oxodG incision activity in the nucleus by decreasing the activity and content of a DNA repair enzyme, Ogg1. These results indicate that APAP in large doses can increase the 8-oxodG level partly through significant reduction of Ogg1 DNA repair enzyme.