Ulrich E M, Willett K L, Caperell-Grant A, Bigsby R M, Hites R A
School of Public and Environmental Affairs and Department of Chemistry, Indiana University, Bloomington, Indiana 47405, USA.
Environ Sci Technol. 2001 Apr 15;35(8):1604-9. doi: 10.1021/es001754g.
Since cyclodextrin gas chromatography columns became popular for chiral separations, many researchers have noticed high enantiomeric ratios [ER: (+)-enantiomer/(-)-enantiomer] for alpha-HCH in the brains of wildlife. This investigation used the laboratory rat as a model for these phenomena. Rats were either pretreated with phenobarbital (PB) or left untreated and then dosed with alpha-HCH. Animals were sacrificed after 1 or 24 h. The ER averaged 0.95 +/- 0.01 in blood, 1.29 +/- 0.02 in fat, and 0.77 +/- 0.004 in liver. ERs in brain ranged from 2.8 +/- 0.5 to 13.5 +/- 0.4. Both the tissue concentration distribution and the ERs agree well with those previously reported in wildlife. To determine whether high brain ERs were due to enantioselective metabolism or transport through the blood-brain barrier, alpha-HCH exposed brain and liver tissue slices were compared. Concentrations in the brain slices did not decrease with PB pretreatment but did decrease in the liver slices. Enantiomeric ratios in the brain slices averaged 1.11 +/- 0.02 and were 0.76 +/- 0.03 in liver slices for the PB pretreated rats. These data indicate that the enantioselective metabolism of alpha-HCH by the brain is not the mechanism responsible for high ERs in this tissue.
自从环糊精气相色谱柱在对映体分离中流行起来后，许多研究人员注意到野生动物大脑中α-六氯环己烷的对映体比例[ER：(+)-对映体/(-)-对映体]很高。本研究以实验室大鼠作为这些现象的模型。大鼠要么用苯巴比妥（PB）预处理，要么不进行处理，然后给予α-六氯环己烷。在1或24小时后处死动物。血液中的ER平均为0.95±0.01，脂肪中为1.29±0.02，肝脏中为0.77±0.004。大脑中的ER范围为2.8±0.5至13.5±0.4。组织浓度分布和ER与之前在野生动物中报道的结果都非常吻合。为了确定大脑中高ER是否是由于对映体选择性代谢或通过血脑屏障的转运，比较了暴露于α-六氯环己烷的大脑和肝脏组织切片。大脑切片中的浓度在PB预处理后没有降低，但肝脏切片中的浓度降低了。对于PB预处理的大鼠，大脑切片中的对映体比例平均为1.11±0.02，肝脏切片中为0.76±0.03。这些数据表明，大脑对α-六氯环己烷的对映体选择性代谢不是该组织中高ER的原因。
