Lack of aldehyde dehydrogenase ameliorates oxidative stress induced by single-dose ethanol administration in mouse liver.
Polymorphism of aldehyde dehydrogenase 2 (ALDH2), denoted ALDH2*2, is far more common in East Asian countries. Acetaldehyde, an intermediate metabolite of ethanol, is metabolized very slowly in people who have ALDH2*2, 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.
Matsumoto
Akiko
A
Department of Social and Environmental Medicine, Saga Medical School, Saga 849-8501, Japan. matsumoa@cc.saga-u.ac.jp
Ichiba
Masayoshi
M
Horita
Mikako
M
Yamashita
Zenko
Z
Takahashi
Tatsuya
T
Isse
Toyohi
T
Oyama
Tsunehiro
T
Kawamoto
Toshihiro
T
Tomokuni
Katsumaro
K
D000284:Administration, Oral; D000444:Aldehyde Dehydrogenase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000818:Animals; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000494:pharmacology*; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000187:drug effects*; D013997:Time Factors
D002492:Central Nervous System Depressants; D000431:Ethanol; D008315:Malondialdehyde; C515029:ALDH2 protein, mouse; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D005978:Glutathione