Aldehyde Dehydrogenase 2 Gene Targeting Mouse Lacking Enzyme Activity Shows High Acetaldehyde Level in Blood, Brain, and Liver after Ethanol Gavages

Isse, Toyohi; Matsuno, Koji; Oyama, Tsunehiro; Kitagawa, Kyoko; Kawamoto, Toshihiro

doi:10.1097/01.alc.0000187161.07820.21

Cited by 93 publications

(94 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…14) Our previous study revealed that murine ALDH2 is important for acetaldehyde metabolism and that Aldh2 -/-mice have significantly higher acetaldehyde levels after ethanol exposure compared with Aldh2 +/+ mice. 15) It is also known that CAT and other AOEs may be inactivated by free radicals produced by ethanol metabolism. 16) The GPx enzyme works in tandem with CAT to scavenge excess H 2 O 2 and lipid peroxides in response to oxidative stress.…”

Section: Resultsmentioning

confidence: 99%

Activities of Antioxidant Enzymes Induced by Ethanol Exposure in Aldehyde Dehydrogenase 2 Knockout Mice

Eom

Zhang

Ogawa

et al. 2007

JOURNAL OF HEALTH SCIENCE

Self Cite

View full text Add to dashboard Cite

Acetaldehyde production during ethanol metabolism has been implicated as an important link between oxidative stress and cell damage, which suggests that oxidative stress caused by ethanol exposure may be more severe in aldehyde dehydrogenase 2 (ALDH2)-deficient individuals than in those with wild-type ALDH2. We evaluated the activities of the major antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), in liver tissue isolated from Aldh2 +/+ and Aldh2 -/-mice that were exposed to ethanol. The activities of CAT and GPx were significantly increased by ethanol treatment in Aldh2 +/+ mice (3.33-fold and 1.65-fold, respectively). The mean activity of SOD in Aldh2 +/+ mice was 1.46-fold that in the Aldh2 +/+ control group, but the difference was not statistically significant. In Aldh2 -/-mice, the activities of SOD and CAT were decreased and that of GPx was slightly increased after ethanol exposure, but the differences were not significant. We postulate that antioxidant enzyme expression after ethanol consumption may differ according to the intracellular level of acetaldehyde or free radicals, which in turn depends on the activity of ALDH2. These results suggest that the greater toxicity of ethanol in Aldh2 -/-mice than in Aldh2 +/+ mice may be due to decreased antioxidant enzyme expression.

show abstract

Section: Resultsmentioning

confidence: 99%

Activities of Antioxidant Enzymes Induced by Ethanol Exposure in Aldehyde Dehydrogenase 2 Knockout Mice

Eom

Zhang

Ogawa

et al. 2007

JOURNAL OF HEALTH SCIENCE

Self Cite

View full text Add to dashboard Cite

show abstract

“…To confirm this hypothesis, we used Aldh2 knockout mice as an ALDH2 inactive human model for detecting the influence of the polymorphisms of the Aldh2 gene on the reproductive toxicity of EGEE in males. Aldh2 knockout mice were created by transgenic knockout of the Aldh2 gene in mice of C57BL/6 background, and the knockout mice (Aldh2-/-) showed little in vitro activity with regard to aldehydes of low molecular weight in the mitochondrial fraction of the liver 6,9) . Male Aldh2 knockout mice (Aldh2-/-) and mice of the wild-type C57BL/6 (Aldh2 +/+), 12 wk old, were used.…”

mentioning

confidence: 99%

Reproductive Toxicity of Ethylene Glycol Monoethyl Ether in Aldh2 Knockout Mice

et al. 2007

Self Cite

View full text Add to dashboard Cite

Ethylene glycol monoethyl ether (EGEE) can cause damage to testes and sperm, and its metabolites are believed to play an important role in its toxicity. Aldehyde dehydrogenase 2 (ALDH2) is involved in the metabolism of this chemical. To investigate whether and how the enzyme affects the toxicity of EGEE, we conducted experiments comparing Aldh2 knockout mice with wild-type mice. Administration of EGEE at 100 and 600 mg/kg/day for one week did not induce any significant change in the weight and body weight ratios of testes, prostate and epididymides in either Aldh2 knockout or wild-type mice. However, motion of sperm from the spermaduct, as analyzed with a Hamilton-Thorne Sperm analyzer, was slightly decreased in the low dose group, and significantly lower in the high dose group; and the percentage of progressive sperm was also reduced in the two EGEE groups. This effect of EGEE treatment was observed in the wild-type, but not in the Aldh2 knockout mice. Sperm motion from the cauda epididymides was not affected. On the other hand, the concentration of ethoxyacetic acid, a metabolite of EGEE, in 24 h pooled urine of EGEE-treated Aldh2 knockout mice was not significantly lower than that of the wild-type mice on most days of urine sampling. These results suggest that inactivation of the ALDH2 enzyme due to gene mutation may be linked to differences in the susceptibility to EGEE-induced sperm toxicity.

show abstract

“…Zhang et al 21) recently reported that a 24 h exposure to acetaldehyde significantly enhanced intracellular ROS generation in cultured myocytes. On the basis of these facts, we hypothesized that ALDH2-deficient individuals may be more susceptible to ethanol-induced oxidative stress than ALDH2 wild-type individuals because ALDH2-deficient individuals have higher blood acetaldehyde concentrations than ALDH2 wild-type individuals 11) . The comet assay is considered to be a rapid, sensitive and relatively simple method for detecting DNA damage at the level of individual cells 22) .…”

Section: Discussionmentioning

confidence: 99%

“…After ethanol consumption, the activity of the microsomal ethanol-oxidizing system (MEOS) is increased, with an associated increase in cytochrome P450 activity, especially that of cytochrome P450 2E1 (CYP2E1) 9,10) . However, because the main enzyme for acetaldehyde metabolism is ALDH2 11) , there is a possibility that the activity of the MEOS may differ according to the activity of ALDH2.…”

mentioning

confidence: 99%

Ethanol‐Induced Oxidative DNA Damage and CYP2E1 Expression in Liver Tissue of Aldh2 Knockout Mice

Kim

Eom

Ogawa

et al. 2007

Journal of Occupational Health

Self Cite

View full text Add to dashboard Cite

Aldehyde Dehydrogenase 2 Gene Targeting Mouse Lacking Enzyme Activity Shows High Acetaldehyde Level in Blood, Brain, and Liver after Ethanol Gavages

Abstract: 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.

Cited by 93 publications

References 14 publications

Activities of Antioxidant Enzymes Induced by Ethanol Exposure in Aldehyde Dehydrogenase 2 Knockout Mice

Activities of Antioxidant Enzymes Induced by Ethanol Exposure in Aldehyde Dehydrogenase 2 Knockout Mice

Reproductive Toxicity of Ethylene Glycol Monoethyl Ether in Aldh2 Knockout Mice

Ethanol‐Induced Oxidative DNA Damage and CYP2E1 Expression in Liver Tissue of Aldh2 Knockout Mice

Contact Info

Product

Resources

About