Matsumoto Akiko, Ichiba Masayoshi, Horita Mikako, Yamashita Zenko, Takahashi Tatsuya, Isse Toyohi, Oyama Tsunehiro, Kawamoto Toshihiro, Tomokuni Katsumaro
Department of Social and Environmental Medicine, Saga Medical School, Saga 849-8501, Japan.
Alcohol. 2007 Feb;41(1):57-9. doi: 10.1016/j.alcohol.2007.01.004.
Polymorphism of aldehyde dehydrogenase 2 (ALDH2), denoted ALDH22, is far more common in East Asian countries. Acetaldehyde, an intermediate metabolite of ethanol, is metabolized very slowly in people who have ALDH22, as the mutated ALDH2 lacks acetaldehyde metabolizing activity. On the other hand, it is well established that metabolism of ethanol causes oxidative stress in liver tissue. To examine the consequences of this polymorphism on ethanol-induced oxidative stress in liver tissue, we conducted a study using Aldh2 knockout mice. Aldh2+/+ and Aldh2-/- mice were orally administered ethanol at a dose of 5g/kg body weight. Levels of malondialdehyde, an indicator of oxidative stress, and glutathione, a key antioxidant, in liver tissue were analyzed 0-24h after administration. Levels of malondialdehyde were significantly lower in Aldh2-/- mice than in Aldh2+/+ mice at 12h after injection, while levels of glutathione were higher in Aldh2-/- mice than in Aldh2+/+ mice at 6 and 12h after injection. Our results suggest that a lack of ALDH ameliorates ethanol-induced oxidative stress in liver tissue.
醛脱氢酶2（ALDH2）的多态性，即ALDH22，在东亚国家更为常见。乙醛是乙醇的中间代谢产物，在携带ALDH22的人群中代谢非常缓慢，因为突变的ALDH2缺乏乙醛代谢活性。另一方面，乙醇代谢会在肝脏组织中引起氧化应激，这一点已得到充分证实。为了研究这种多态性对肝脏组织中乙醇诱导的氧化应激的影响，我们使用Aldh2基因敲除小鼠进行了一项研究。给野生型（Aldh2+/+）和基因敲除型（Aldh2-/-）小鼠口服剂量为5g/kg体重的乙醇。在给药后0至24小时分析肝脏组织中氧化应激指标丙二醛（malondialdehyde）和关键抗氧化剂谷胱甘肽（glutathione）的水平。注射后12小时，Aldh2-/-小鼠的丙二醛水平显著低于Aldh2+/+小鼠，而注射后6小时和12小时，Aldh2-/-小鼠的谷胱甘肽水平高于Aldh2+/+小鼠。我们的结果表明，缺乏ALDH可减轻肝脏组织中乙醇诱导的氧化应激。
