Ethanol and Acetaldehyde After Intraperitoneal Administration to Aldh2-Knockout Mice-Reflection in Blood and Brain Levels
Ethanol and Acetaldehyde After Intraperitoneal Administration to Aldh2-Knockout Mice-Reflection in Blood and Brain Levels
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DOI：
10.1007/s11064-015-1788-6
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发表时间：
2016-05-01
影响因子：
4.4
通讯作者：
Kinoshita, Hiroshi
中科院分区：
文献类型：
--
作者：
Jamal, Mostofa;Ameno, Kiyoshi;Kinoshita, Hiroshi
本文首次报道了Aldh 2基因敲除（Aldh 2-KO）和C57 B6/6 J（WT）小鼠血液和脑中乙醇（EtOH）和乙醛（AcH）浓度的分析。动物腹腔注射EtOH（1.0、2.0或4.0 g/kg）或4-甲基吡唑（4-MP，82 mg/kg）加AcH（50、100或200 mg/kg）。在血液测试期间，从眼睛的眶窦收集样本。在脑测试期间，使用体内脑微透析每5分钟从纹状体收集透析液（等于15 μ l样品）。在注射EtOH和-AcH后5、10、15、20、25、30和60分钟间隔收集样品，然后通过顶空GC分析。在EtOH组中，在Aldh 2-KO小鼠的血液和脑中发现高水平的AcH，而在WT小鼠的血液和脑中仅观察到少量的AcH。对于两种EtOH剂量，WT和Aldh 2-KO小鼠之间的EtOH水平均未观察到显着差异。脑中的EtOH浓度与血液中的EtOH浓度相当，但脑中的AcH浓度比血液中的AcH浓度低四到五倍。在AcH组中，在WT和Aldh 2-KO小鼠中均发现高AcH水平。水平达到一个尖锐的峰值，在5分钟，然后迅速下降60分钟。脑乙酰胆碱浓度几乎等于血液中发现的浓度，其中乙酰胆碱浓度约为2倍高的Aldh 2-KO小鼠比野生型小鼠，无论是在血液和大脑。我们的结果表明，全身性EtOH和AcH给药可导致Aldh 2-KO小鼠血液和脑中AcH蓄积的更大增加，其中Aldh 2-KO小鼠中的EtOH浓度与WT小鼠中的EtOH浓度相当。此外，检测乙醇和乙酰胆碱在血液和大脑中被发现是剂量依赖性的两种基因型。
This paper reports, for the first time, on the analysis of ethanol (EtOH) and acetaldehyde (AcH) concentrations in the blood and brains of Aldh2-knockout (Aldh2-KO) and C57B6/6J (WT) mice. Animals were administrated EtOH (1.0, 2.0 or 4.0 g/kg) or 4-methylpyrazole (4-MP, 82 mg/kg) plus AcH (50, 100 or 200 mg/kg) intraperitoneally. During the blood tests, samples from the orbital sinus of the eye were collected. During the brain tests, dialysates were collected every 5 min (equal to a 15 A mu l sample) from the striatum using in vivo brain microdialysis. Samples were collected at 5, 10, 15, 20, 25, 30 and 60 min intervals post-EtOH and -AcH injection, and then analyzed by head-space GC. In the EtOH groups, high AcH levels were found in the blood and brains of Aldh2-KO mice, while only small traces of AcH were seen in the blood and brains of WT mice. No significant differences in EtOH levels were observed between the WT and the Aldh2-KO mice for either the EtOH dose. EtOH concentrations in the brain were comparable to the EtOH concentrations in the blood, but the AcH concentrations in the brain were four to five times lower compared to the AcH concentrations in the blood. In the AcH groups, high AcH levels were found in both WT and Aldh2-KO mice. Levels reached a sharp peak at 5 min and then quickly declined for 60 min. Brain AcH concentrations were almost equal to the concentrations found in the blood, where the AcH concentrations were approximately two times higher in the Aldh2-KO mice than in the WT mice, both in the blood and the brain. Our results suggest that systemic EtOH and AcH administration can cause a greater increase in AcH accumulation in the blood and brains of Aldh2-KO mice, where EtOH concentrations in the Aldh2-KO mice were comparable to the EtOH concentrations in the WT mice. Furthermore, detection of EtOH and AcH in the blood and brain was found to be dose-dependent in both genotypes.