4.2 Article

Effects of 5-week ethanol feeding on the liver of aldehyde dehydrogenase 2 knockout mice

Journal

PHARMACOGENETICS AND GENOMICS
Volume 18, Issue 10, Pages 847-852

Publisher

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/FPC.0b013e328307a0a9

Keywords

acetaldehyde; alanine aminotransferase; aldehyde dehydrogenase; ethanol; extracellular signal-regulated kinases; knockout mice; polymorphism; tumor necrosis factor-alpha

Funding

  1. Ministry of Education, Culture, Sports, Science, and Technology of Japan

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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. Conclusion 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.

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