Thiobarbituric Acid Reactive Substances Levels in Brain Tissue of Aldh2 Knockout Mice Following Ethanol Exposure for 8 Weeks

Abstract

Excessive alcohol consumption causes various degenerative brain diseases including Alzheimer's disease and Parkinson's disease. Absorbed ethanol is metabolized to acetaldehyde and acetic acid by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). Acetaldehyde is well known as a toxicant through generation of reactive oxygen species (ROS). Therefore, ALDH2 activity may play important roles in the pathogenesis of alcohol-induced brain diseases. In this study, we demonstrated the effects of ALDH2 enzyme activity on lipid peroxidation in brain tissues and urine of mice exposed to ethanol for 8 weeks. Five male, 8-week old Aldh2 (+/+) and Aldh2 (-/-) mice (C57BL/6J strain) in each group were exposed to ethanol for 8 weeks (2 g/kg wt./day) using gavage, and those in the control group received 0.9% saline alone. Thiobarbituric acid reactive substances (TBARS) level, a marker for lipid peroxidation, was measured in whole brain tissue and urine by high performance liquid chromatography. As a result, chronic ethanol treatment did not show any statistical change on the TBARS level of brain tissue in both Aldh2 (+/+) mice and in Aldh2 (-/-) mice. However, following ethanol exposure for 8 weeks in Aldh2 (-/-) mice, the urinary TBARS levels were significantly increased to more than double compared to the pretreatment group. This result was not observed in Aldh2 (+/+) mice. These results suggest that although ALDH2 enzyme activity plays a role in the generation of ROS in the whole body, it does not seem to be important in the pathogenesis of alcohol induced degenerative brain diseases.