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

Abstract

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.

Antioxidant Properties of Amaranthus hypochondriacus Seeds and their Effect on the Liver of Alcohol-Treated Rats

“…The expression of CAT mRNA did not exhibit variations; however, the activity of this enzyme showed an increasing tendency, which may indicate that one or more mechanisms of post-transcriptional control might be involved. During ethanol metabolism, cytochrome P450-2E1 (CYP2E1), alcohol dehydrogenase (ADH) and NADPH oxidase (NOX) generate H 2 O 2 , acetaldehyde and superoxide radicals, respectively [33]. The present study demonstrates that NOX-2 transcript level (AU) decrease in group IV as compared to group II (IV: 1.89±0.23; II: 2.72±0.17; p<0.05) (Fig.…”

Hepatic Cytochrome P450 2E1 Level Rather Than Cecal Condition Contributes to Induction of Early Stage of the Alcoholic Liver Damage in Rats

“…7) These findings also suggest that some antioxidant enzymes are associated with protection of the liver from injury. In some cases, pattern of SOD-2 level may be similar to that of catalase level in alcoholic liver disease, 30,31) and in other cases, including this study, these patterns were not same. 32) The main transcriptional factors for expression of each enzyme may differ in this study, as well as in previous reports.…”

“…Accumulation of hepatic lipid and increases in plasma ALT level and/or hepatic TBARS level were observed in ethanol-ingested rats. These are typical indicators for alcoholic liver damage, [30][31][32] and these indicators negatively correlated with hepatic catalase levels. These results suggest that hepatic damage was induced by the in- …”

“…30) Contrary to the reduction in catalase levels in the ethanol-ingested rats, some studies had indicated no reduction in catalase activity in ethanoltreatment although experimental desings had been different from this study. 31,35,36) Considering these data, protective role of catalase in hepatic damages should be investigated in further studies.…”

Ethanol stimulates epithelial sodium channels by elevating reactive oxygen species

“…These observations imply that the presence of aldehydes is intimately related to the production of ROS. In fact, aldehydes are known to inhibit both superoxide dismutase (11) and catalase (40), the inhibition of which would lead to increased cellular levels of superoxide and hydrogen peroxide.…”