Oxidative stress, metabolism of ethanol and alcohol-related diseases

Zima, Tomáš; Fialová, L; Mestek, Oto; Janebová, Marta; Crkovská, J; Malbohán, I; Stípek, S; Mikulíková, L; Popov, Petr

doi:10.1007/bf02255972

Cited by 282 publications

(99 citation statements)

References 67 publications

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“…26) Oxidative stress is characterized by increased lipid peroxidation and/or altered nonenzymatic and enzymatic antioxidant systems. The effects of exposing mice to the chronic regime of alcohol on various antioxidant defences and lipid peroxides were investigated in the liver.…”

Section: Resultsmentioning

confidence: 99%

Quercetin, a Flavonoid Antioxidant, Prevents and Protects against Ethanol-Induced Oxidative Stress in Mouse Liver

Aguado

Sánchez-Reus²,

Iglesias

et al. 2003

Biological & Pharmaceutical Bulletin

253

145

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Flavonoids are a group of naturally occurring compounds widely distributed as secondary metabolites in the plant kingdom. They have been recognized for having interesting clinical properties, such as anti-inflammatory, antiallergic, antiviral, antibacterial, and antitumoral activities. 1) In fact, the pharmacological effects of many traditional drugs may be ascribed to the presence of flavonoid compounds, which 2,3) are due to the inhibiting ability of certain enzymes and their antioxidant activity.One to these flavonoids, quercetin (3,5,7,3Ј,4Ј-pentahydroxyflavone), prevents oxidant injury and cell death 4) by several mechanisms, such as scavenging oxygen radicals 5,6) protecting against lipid peroxidation 7,8) and chelating metal ions.9) Some investigators have demonstrated that quercetin, when coadministered with ethanol, reduced ethanol-induced hepatic steatosis and lipid peroxidation, suggesting that the gastroprotective effect of quercetin could be due to its antiperoxidative, antioxidant, and antihistaminic effects. [10][11][12] Experimental evidence has demonstrated that some of the deleterious effects of ethanol are attributed to the induction of metabolic processes which lead to an increase in the generation of reactive oxygen species (ROS). 13,14) In hepatocytes, ROS are generated, as a consequence of the metabolism of ethanol to acetaldehyde, mainly through the intervention of the ethanol-inducible cytochrome P450 (CYP2El). 15)Organisms have developed a variety of antioxidant defence systems as a protection from ROS. The major endogenous antioxidant enzyme systems include superoxide dismutase (SOD), catalase (CAT), selenium-dependent glutathione peroxidase (GPx-Se), glutathione peroxidase (GPx), and glutathione reductase (GR). The major nonenzymatic endogenous antioxidants include the reduced form of glutathione (GSH) and vitamin E. However, ethanol or its metabolites can alter the redox balance in the liver towards a more oxidized state, either acting as a prooxidant or reducing the antioxidant cell defences. 16) On the basis of these considerations, the aim of the present study was to evaluate if quercetin and vitamin E (a-tocopherol, reference substance) treatments have a protective effect in alcoholic liver injury in mice. In this study, these substances were administered either before or following ethanol intoxication in order to determine whether they could prevent and/or alleviate ethanol-induced injury. Our hypothesis is that increasing the diet antioxidant concentration may make it possible to prevent the incidence of alcoholic diseases. MATERIALS AND METHODS AnimalsMale Swiss mice aged 7-12 weeks were used in all experiments and were housed under controlled environmental conditions (12 h light/12 h dark). The animals were permitted unlimited access to food and water. A group of animals used to determine the effects of chronic exposure to alcohol was given ethanol by intragastric administration for 30 d. Ethanol (5 g/kg of body weight) was diluted (18% v/v) in water. Quercetin and vitamin E ...

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Section: Resultsmentioning

confidence: 99%

Quercetin, a Flavonoid Antioxidant, Prevents and Protects against Ethanol-Induced Oxidative Stress in Mouse Liver

Aguado

Sánchez-Reus²,

Iglesias

et al. 2003

Biological & Pharmaceutical Bulletin

253

145

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“…8,9) Oxidative stress is characterized by increased lipid peroxidation and/or altered nonenzymatic and enzymatic antioxidant systems. However, conflicting results are reported in the literature concerning oxidative stress following chronic ethanol treatment in rats.…”

Section: Resultsmentioning

confidence: 99%

“…Oxidative stress is known to play an important role in the pathogenesis of ethanol-induced liver injury. 8,9) Several experimental [10][11][12][13] and clinical 14) studies have shown that ethanol ingestion alters the prooxidant-antioxidant balance in the organism. Therefore the potential role of several substances such as antioxidants 15,16) and thiol compounds 5,12,13) has been investigated in ethanol-induced liver injury.…”

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confidence: 99%

Taurine Treatment Reduces Hepatic Lipids and Oxidative Stress in Chronically Ethanol-Treated Rats.

Balkan

Kanbagli

Aykaç‐Toker

et al. 2002

Biological & Pharmaceutical Bulletin

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Taurine (2-aminoethane sulfonic acid), a nonprotein amino acid, has hypolipidemic 1) and antiatherosclerotic effects. 2,3) In addition, taurine has been thought to be a hepatoprotective agent.4) Some investigators have demonstrated that taurine, when coadministered with ethanol, reduced ethanol-induced hepatic steatosis and lipid peroxidation. 5) Our recent studies have also shown that taurine treatment has a protective effect against thioacetamide-induced hepatic necrosis 6) and cirrhosis 7) by decreasing oxidative stress. Oxidative stress is known to play an important role in the pathogenesis of ethanol-induced liver injury. 8,9) Several experimental [10][11][12][13] and clinical 14) studies have shown that ethanol ingestion alters the prooxidant-antioxidant balance in the organism. Therefore the potential role of several substances such as antioxidants 15,16) and thiol compounds 5,12,13) has been investigated in ethanol-induced liver injury. The aim of the present study was to evaluate whether taurine treatment has a protective effect in postalcoholic liver injury in rats. For this reason, hepatic lipid levels as well as prooxidant and antioxidant status were determined in rats that received taurine 28 d after cessation of chronic ethanol ingestion. MATERIALS AND METHODS Rats and TreatmentMale Wistar rats (180-200 g) were used for all experiments. Animals were obtained from the Experimental Medical Research Institute of Istanbul University. Rats were fed a standard diet and had free access to water. Ethanol was added to drinking water 20% (v/v) for 3 months (approximately 8.5 g ethanol/kg body weight/d). Control rats (nϭ8) were given tap water as drinking fluid.At the end of this period, some rats were killed after overnight fasting. Other rats were divided into two groups. The first group did not receive any treatment, but the second group received taurine for 28 d after ethanol cessation. Taurine treatment was performed by adding taurine to the drinking water 1% (w/v) plus injection (400 mg/kg body weight) intraperitoneally 3 times per week. Experimental Procedure and DeterminationsBlood samples were collected from animals by cardiac puncture and serum transaminase (ALT and AST) activities were determined using kits from Sigma. The livers were rapidly removed, washed in 0.9% NaCl and kept in ice. Liver portions were homogenized in ice-cold 0.15 M KCI 10% (w/v). Lipids were extracted by chloroform : methanol (2 : 1) and hepatic total lipid levels were measured according to the methods of Chiang et al. 17) Hepatic triglyceride levels were determined in the lipid extracts with kits from Sigma. The degree of lipid peroxidation was assessed measuring malondialdehyde (MDA) levels using the thiobarbituric acid test 18) and diene conjugate levels.19) Liver glutathione (GSH) levels were measured with 5,5Ј-dithiobis-(2-nitrobenzoate) at 412 nm according to the method of Beutler et al. 20) Liver vitamin E and vitamin C levels were determined in homogenates by the method of Desai 21) and Omaye et al., 22) respectiv...

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“…The availability of both transgenes has made it possible to examine the precise mechanism(s) of acetaldehyde in alcoholic tissue and cell injury. Although several hypotheses have been postulated for alcohol toxicity including oxidative damage, lipid peroxidation and altered membrane property due to hydrophobic ethanol interaction with membrane components (23)(24)(25), the culprit toxin in alcoholic tissue and cell injury, has not been clearly identified and thus hindered proper treatment and prevention of alcoholic complications. Ethanol has been demonstrated to contribute to oxidative stress and enhanced peroxidation of lipids, protein, and DNA in a wide variety of organs, tissues, and cells (23)(24)(25)(26).…”

Section: Discussionmentioning

confidence: 99%

“…Although several hypotheses have been postulated for alcohol toxicity including oxidative damage, lipid peroxidation and altered membrane property due to hydrophobic ethanol interaction with membrane components (23)(24)(25), the culprit toxin in alcoholic tissue and cell injury, has not been clearly identified and thus hindered proper treatment and prevention of alcoholic complications. Ethanol has been demonstrated to contribute to oxidative stress and enhanced peroxidation of lipids, protein, and DNA in a wide variety of organs, tissues, and cells (23)(24)(25)(26). Similarly, the ethanol metabolite acetaldehyde directly enhances free radical generation by its oxidation via aldehyde oxidase and/or xanthine oxidase with concurrent accumulation of superoxide (25,(27)(28)(29).…”

Section: Discussionmentioning

confidence: 99%

Overexpression of Aldehyde Dehydrogenase-2 (ALDH2) Transgene Prevents Acetaldehyde-induced Cell Injury in Human Umbilical Vein Endothelial Cells

Gomelsky

Duan

et al. 2004

Journal of Biological Chemistry

109

104

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Acetaldehyde, the major ethanol metabolite that is far more toxic and reactive than ethanol, has been postulated to be responsible for alcohol-induced tissue and cell injury. This study was to examine whether facilitated acetaldehyde metabolism affects acetaldehyde-induced oxidative stress and apoptosis. Transgene-encoding human aldehyde dehydrogenase-2 (ALDH2), which converts acetaldehyde into acetate, was constructed under chicken ␤-actin promoter and transfected into human umbilical vein endothelial cells (HUVECs). Efficacy of ALDH2 transfection was verified using green fluorescent protein and ALDH2 enzymatic assay. Generation of reactive oxygen species (ROS) was measured using chloromethyl-2,7-dichlorodihydrofluorescein diacetate. Apoptosis was evaluated by 4,6-diamidino-2-phenylindoladihydrochloride fluorescence microscopy, quantitative DNA fragmentation, and caspase-3 assay. Acetaldehyde (0 -200 M) elicited ROS generation and apoptosis in HUVECs in a time-and concentration-dependent manner, associated with activation of the stress signal molecules ERK1/2 and p38 mitogen-activated protein (MAP) kinase. A close liner correlation was observed between the acetaldehyde-induced ROS generation and apoptosis. Interestingly, the acetaldehydeinduced ROS generation, apoptosis, activation of ERK1/2, and p38 MAP kinase were prevented by the ALDH2 transgene or antioxidant ␣-tocopherol. The involvement of ERK1/2 and p38 MAP kinase in acetaldehyde-induced apoptosis was confirmed by selective kinase inhibitors U0126, SB203580, and SB202190. Collectively, our data revealed that facilitation of acetaldehyde metabolism by ALDH2 transgene overexpression may prevent acetaldehyde-induced cell injury and activation of stress signals. These results indicated therapeutic potential of ALDH2 enzyme in the prevention and detoxification of acetaldehyde or alcohol-induced cell injury.Chronic alcohol consumption leads to cardiovascular complications such as endothelial dysfunction and alcoholic cardiomyopathy (1). Although several hypotheses have been speculated for alcohol-induced injury including direct/indirect toxicity of alcohol and accumulated fatty acid ethyl esters (2, 3), neither scenario has been fully validated by compelling clinical and experimental evidence. Acetaldehyde is the very first oxidized metabolic product of ethanol and is considered a candidate toxin for alcohol-induced tissue and cell injury. It is far more reactive than ethanol and may inhibit protein synthesis (4, 5). Our laboratory (6 -8) has shown that acetaldehyde interrupts cardiac excitation-contraction coupling and sarco(endo)plasmic reticulum Ca 2ϩ release function. Acetaldehyde has also been shown to form protein adducts leading to atherosclerotic vascular injury (9). Transgenic mice with cardiac overexpression of alcohol dehydrogenase (ADH) 1 displayed higher cardiac acetaldehyde levels associated with compromised heart function at whole heart and ventricular myocyte levels following alcohol intake (10 -12), suggesting that acetaldehyde may be one of t...

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Oxidative stress, metabolism of ethanol and alcohol-related diseases

Cited by 282 publications

References 67 publications

Quercetin, a Flavonoid Antioxidant, Prevents and Protects against Ethanol-Induced Oxidative Stress in Mouse Liver

Quercetin, a Flavonoid Antioxidant, Prevents and Protects against Ethanol-Induced Oxidative Stress in Mouse Liver

Taurine Treatment Reduces Hepatic Lipids and Oxidative Stress in Chronically Ethanol-Treated Rats.

Overexpression of Aldehyde Dehydrogenase-2 (ALDH2) Transgene Prevents Acetaldehyde-induced Cell Injury in Human Umbilical Vein Endothelial Cells

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