Effects of 5-week ethanol feeding on the liver of aldehyde dehydrogenase 2 knockout mice.
OBJECTIVE
The polymorphism of aldehyde dehydrogenase 2 (ALDH2), denoted ALDH2*2, is very common in East Asian countries, and the mutated ALDH2 protein derived from ALDH2*2 lacks the ability of acetaldehyde metabolization. Our aim was to determine the consequences of the ALDH2 polymorphism on ethanol-administered liver tissue.


METHODS
Aldh2+/+, +/-, and -/- mice were fed with ethanol solution and standard hard feed for 5 weeks.


RESULTS
The serum alanine aminotransferase (ALT) level in the Aldh2-/- mice clearly decreased upon ethanol feeding, in contrast to Aldh2+/+ mice, in which the ALT level was unchanged. The levels of malondialdehyde, phospho extracellular signal-regulated kinase 2, and tumor necrosis factor-alpha in the liver tissue all correlated with the ALT level.


CONCLUSIONS
These findings suggest that ethanol intake in the presence of inactive ALDH2 decreases the serum ALT level following a decrease in oxidative stress and tumor necrosis factor-alpha secretion.
Matsumoto
Akiko
A
Departments of Social and Environmental Medicine, Saga Medical School, Saga, Japan. matsumoa@cc.saga-u.ac.jp
Kawamoto
Toshihiro
T
Mutoh
Fumihiro
F
Isse
Toyohi
T
Oyama
Tsunehiro
T
Kitagawa
Kyoko
K
Nakayama
Keiichi I
KI
Ichiba
Masayoshi
M
D000079:Acetaldehyde / Q000378:metabolism; D000410:Alanine Transaminase / Q000097:blood*; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000821:Animal Feed; D000818:Animals; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D008099:Liver / Q000201:enzymology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D018384:Oxidative Stress; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol; C515029:ALDH2 protein, mouse; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000410:Alanine Transaminase; D000079:Acetaldehyde