Aldehyde dehydrogenase 2 gene targeting mouse lacking enzyme activity shows high acetaldehyde level in blood, brain, and liver after ethanol gavages.
BACKGROUND
Previously, we created an aldehyde dehydrogenase 2 gene transgenic (Aldh2-/-) mouse as an aldehyde dehydrogenase (ALDH) 2 inactive human model and demonstrated low alcohol preference. In addition, after a free-choice drinking test, no difference in the acetaldehyde level was observed between the Aldh2-/- and wild type (Aldh2+/+) mice. The actual amounts of free-choice drinking were so low that it is uncertain whether these levels are pharmacologically and/or behaviorally relevant in either strain. To elucidate this uncertainty, we compared the ethanol and acetaldehyde concentration in the blood, brain, and liver between the Aldh2-/- and Aldh2+/+ mice after ethanol gavages at the same dose and time.


METHODS
We measured differences in the ethanol and acetaldehyde levels between the Aldh2-/- and Aldh2+/+ mice by headspace gas chromatography-mass spectrometry (GC-MS) after ethanol gavages at the same dose and time.


RESULTS
Significantly higher blood acetaldehyde concentrations were found in the Aldh2-/- mice than in the Aldh2+/+ mice 1 hr after the administration of ethanol gavages at doses of 0.5, 1.0, 2.0, and 5.0 g/kg. The blood acetaldehyde concentrations in the two strains were 2.4 vs. 0.5, 17.8 vs. 1.9, 108.3 vs. 4.3, and 247.2 vs. 14.0 (microM), respectively. In contrast, no significant difference was observed in the blood ethanol concentrations between the Aldh2+/+ and Aldh2-/- mice. The aldehyde dehydrogenase 2 enzyme metabolized 94% of the acetaldehyde produced from the ethanol as calculated from the area under the curve (AUC) of acetaldehyde when ethanol was administered at a dose of 5.0 g/kg.


CONCLUSIONS
These data indicate that mouse ALDH2 is a major enzyme for acetaldehyde metabolism, and the Aldh2-/- mice have significantly high acetaldehyde levels after ethanol gavages.
Isse
Toyohi
T
Department of Environmental Health, School of Medicine, the Bio-information Research Center, University of Occupational and Environmental Health, Kitakyushu, Japan.
Matsuno
Koji
K
Oyama
Tsunehiro
T
Kitagawa
Kyoko
K
Kawamoto
Toshihiro
T
D000079:Acetaldehyde / Q000097:blood*; D000284:Administration, Oral; D000428:Alcohol Drinking / Q000097:blood / Q000235:genetics; D000444:Aldehyde Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D019540:Area Under Curve; D001921:Brain / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage* / Q000097:blood / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013045:Species Specificity; D014867:Water / Q000008:administration & dosage
D014867:Water; D000431:Ethanol; D000444:Aldehyde Dehydrogenase; D000079:Acetaldehyde