A pilot study on subacute ethanol treatment of ALDH2 KO mice.
Aldh (aldehyde dehydrogenase ) 2 knockout (KO) mice have been generated in our laboratory. We evaluated the effects of subacute ethanol treatment on the survival rate, expression of Aldh1, Aldh2, Cytochrome P450 (Cyp) 1A1, Cyp2e1 and Cyp4b1 in wild (Aldh2+/+) mice (C57BL/6) and Aldh2 knock out (Aldh2-/-) mice. Physiological saline (0.3 mL/day) was administered to 4 Aldh2+/+ and 4 Aldh2-/- mice for 8 days as a control. Forty percent ethanol (0.3 mL/day; ethanol 2 g/kg/day) was then administered to 5 Aldh2+/+ and 9 Aldh2-/- mice for 8 days. Three mice of the ethanol administered Aldh2+/+ group and eight mice of the ethanol administered Aldh2-/- group died during the 8 days. The weights of mice were decreased by ethanol exposure to 85% and 74% in Aldh2+/+ and Aldh2-/- group, respectively. The survival rates of the ethanol administered Aldh2+/+ and Aldh2-/- group were 40 and 11%. Liver and pancreas disorder was revealed in the ethanol administered Aldh2+/+ and Aldh2-/- group in the results of serum chemical examination, immunohistochemical staining and western blot analysis. Cyp2e1 is more inducible to ethanol toxicity in Aldh2-/- mice compared with Aldh2+/+ mice when ethanol is administered according to the results of quantitative PCR.
Oyama
Tsunehiro
T
Kim
Yong-Dae
YD
Isse
Toyohi
T
Phuong
Pham Thi Thu
PT
Ogawa
Masanori
M
Yamaguchi
Tetsunosuke
T
Kinaga
Tsuyoshi
T
Yashima
Yasunori
Y
Kim
Heon
H
Kawamoto
Toshihiro
T
D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000818:Animals; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics; D064420:Drug-Related Side Effects and Adverse Reactions / Q000139:chemically induced* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D000431:Ethanol / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010179:Pancreas / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D010865:Pilot Projects; D016133:Polymerase Chain Reaction; D016019:Survival Analysis; D018675:Toxicity Tests / Q000379:methods*
D000431:Ethanol; D019392:Cytochrome P-450 CYP2E1; C515029:ALDH2 protein, mouse; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial