• Title/Summary/Keyword: Aldehyde dehydrogenase 2

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Sex-specific differences in the association of a common aldehyde dehydrogenase 2 gene polymorphism and alcohol consumption with stroke risk in a Korean population: a prospective cohort study

  • Shin, Chol;Kwack, KyuBum;Cho, Nam H.;Kim, Seong Hwan;Baik, Inkyung
    • Nutrition Research and Practice
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    • v.9 no.1
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    • pp.79-86
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    • 2015
  • BACKGROUND/OBJECTIVES: It is well-known that alcohol consumption is associated with stroke risk as well as with aldehyde dehydrogenase 2 gene (ALDH2) polymorphisms. However, it is unclear whether ALDH2 polymorphisms are associated with stroke risk independent of alcohol consumption and whether such association is modified by sex. We evaluated sex-specific associations of a common ALDH2 polymorphism and alcohol consumption with stroke risk in a Korean population. SUBJECTS/METHODS: We conducted a prospective cohort study involving 8,465 men and women, aged 40-69 years and free of stroke between June, 2001 and January, 2003, and followed for the development of stroke. We identified new cases of stroke, which were self-reported or ascertained from vital registration data. Based on genome-wide association data, we selected a single-nucleotide polymorphism (rs2074356), which shows high linkage disequilibrium with the functional polymorphism of ALDH2. We conducted Cox proportional hazards regression analysis considering potential risk factors collected from a baseline questionnaire. RESULTS: Over the median follow-up of 8 years, 121 cases of stroke were identified. Carrying the wild-type allele of the ALDH2 polymorphism increased stroke risk among men. The multivariate hazard ratio [95% confidence interval] of stroke was 2.02 [1.03-3.99] for the wild-type allele compared with the mutant alleles, but the association was attenuated after controlling for alcohol consumption. Combinations of the wild-type allele and other risk factors of stroke, such as old age, diabetes mellitus, and habitual snoring, synergistically increased the risk among men. Among women, however, the ALDH2 polymorphism was not associated with stroke risk. CONCLUSIONS: The prospective cohort study showed a significant association between a common ALDH2 polymorphism and stroke risk in Korean men, but not in Korean women, and also demonstrated that men with genetic disadvantages gain more risk when having risk factors of stroke. Thus, these men may need to make more concerted efforts to control modifiable risk factors of stroke.

Anti-Diabetic, Alcohol Metabolizing Enzyme, and Hepatoprotective Activity of Acer tegmentosum Maxim. Stem Extracts (산겨릅나무 줄기 추출물의 항당뇨, 알코올 대사 효소 및 간 보호 활성)

  • Cho, Eun Kyung;Jung, Kyung Im;Choi, Young Ju
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.44 no.12
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    • pp.1785-1792
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    • 2015
  • This study was carried out to investigate the antidiabetic, alcohol metabolism, anti-inflammatory, and hepatoprotective effects of Acer tegmentosum extracts (ATE). A. tegmentosum has been traditionally used as a folk medicine to treat hepatic disorders. The antioxidative activities of ATE were measured by using 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity and superoxide (SOD) assay. DPPH radical scavenging and SOD activities of ATE were about 89% and 82.9% at $0.5{\mu}g/mL$, respectively. Alcohol dehydrogenase and acetaldehyde dehydrogenase activities were 118.0% and 177% at 2 mg/mL, respectively. ${\alpha}-Glucosidase$ inhibitory activity of ATE was 75% higher at $50{\mu}g/mL$ and remarkably increased in a dose-dependent manner. Nitric oxide productions in macrophage RAW 264.7 cells stimulated by lipopolysaccharide was reduced to 16.7% by addition of ATE at 1 mg/mL. ATE showed significant protective effects against tacrine-induced cytotoxicity in Hep G2 cells at $100{\mu}g/mL$. Based on our results, we conclude that ATE may be used as a major pharmacological agent and anti-diabetic, anti-hepatitis, and anti-inflammatory remedy.

Cellular Distribution and Metabolism of Ginsenosides in Rat Liver (쥐 간에서의 Ginsenoside의 세포내 분포와 대사)

  • 윤수희;이희봉
    • Journal of Ginseng Research
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    • v.17 no.2
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    • pp.114-122
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    • 1993
  • 0.5 mg of natural ginsenoside mixture and 0.8 $\mu$Ci of synthesized 14C-ginsenosides were administered orally to a rat and killed at one hour after the ginsenoside administration and the liver was fractionated into nuclear fraction, mitrochondria microsomes and cytosol fraction. Radioactivity distribu lion in subcellular fractions of the liver showed that 32o1c of total radioactivity absorbed in the liver was in cytosol fraction but a significant portion of the radioactivity was also found in mitochondria (26.6%) and microsomal fraction (18.l%). 5.8% of the total radioactivity was recovered from the nuclear fraction as well. This suggested that ginsenosides might be distributed into all subcellular fractions. Activities of mitochondrial aldehyde dehydrogenase, lactate dehydrogenase and malate dehydrogenase of the liver of rat at two hours after the ginsenoside administraion were found appreciably stimulated, suggesting that the ginsenoside concentration in the liver might be around 10-5%, since optimum concentrations for most enzyme catalyzed reactions in vitro were known to be 10-6% 10-4%. A significant portion of the radioactivity recovered from subcellular fractions of the liver was found in protein fractions, suggesting that proteins might interact with ginsenosides. Examination of protein-ginsenoside interation by gel filtration, equilibrium dialysis and amonium sulfate precipitation technique suggesting that proteins and ginsenosides do not bound covalently but weakl\ulcorner combined. When purified ginsenoside Rbl and Rgl were incubated with rat liver cytosolic enzymes for 20 min, the above ginsenosides were hydrolyzed quickly, suggesting that ginsenosides might be rapidly hydrolyzed and metabolized in the liver. It was also observed in vitro that the ginsenosides such as Rbl and Rgl were easily hydrolyzed by rat liver cytosol preparation suggesting that absorbed ginsenosides might be quickly hydrolyzed and metabolized in the liver.

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A case of Hypothermia Resulting from Disulfiram-Ethanol Reaction (다이설피람-에탄올 반응에 의한 저체온증 1례)

  • Bae, Hyun-A;Eo, Eun-Kyung
    • Journal of The Korean Society of Clinical Toxicology
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    • v.2 no.1
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    • pp.54-57
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    • 2004
  • Disulfiram (tetraethylthiuram disulphid) is used in the treatment of chronic alcoholism since it causes an unpleasant aversive reaction to alcohol. It works by inactivating hepatic aldehyde dehydrogenase, leading to pronounced rise in the acetaldehyde concentration when ethanol is metabolized. Acetaldehyde causes alcohol sensitivity, which involve vasodilation associated with feeling of hotness and facial flushing, increased heart rate and respiration rates, lowered blood pressure, nausea, headache. One of its metabolites, diethyldithiocarbamate (DDC) can inhibit the enzyme dopamine $\beta$-hydroxylase (DBH), this may account for the profound refractory hypotension and hypothermia seen with the disulfiram-ethanol reaction (DER), resulting from norepinephrine depletion. This report is presents the case of a patient we met, who presented with hypothermia caused by the disulfiram-ethanol reaction, and along with a brief review of the subject.

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Effects of Scopoletin Supplementation on Insulin Resistance and Antioxidant Defense System in Chronic Alcohol-Fed Rats (Scopoletin 보충이 만성 알코올을 급여한 흰쥐의 인슐린저항성 및 항산화방어계에 미치는 영향)

  • Lee, Hae-In;Lee, Mi-Kyung
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.44 no.2
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    • pp.173-181
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    • 2015
  • This study investigated the effects of scopoletin (6-methoxy-7-hydroxycoumarin) supplementation on insulin resistance and the antioxidant defense system in chronic alcohol-fed rats. Rats were fed a Lieber-Decarli liquid diet containing 5% ethanol with or without two doses of scopoletin (0.01 and 0.05 g/L) for 8 weeks. Pair-fed rats received an isocaloric carbohydrate liquid diet. Chronic alcohol did not affect fasting serum glucose levels, although it induced glucose intolerance and hyperinsulinemia compared with the pair-fed group and led to insulin resistance. Both doses of scopoletin similarly improved glucose intolerance, serum insulin level, and insulin resistance. Scopoletin supplementation significantly activated phosphatidyl inositol 3-kinase, which was inhibited by chronic alcohol. Two doses of scopoletin up-regulated hepatic mRNA expression and activity of glucokinase as well as down-regulated mRNA expression and activity of glucose-6-phosphatase compared with the alcohol control group. Both doses of scopoletin significantly reduced cytochrome P450 2E1 activity and elevated aldehyde dehydrogenase 2 activity, resulting in a lower serum acetaldehyde level compared with the alcohol control group. Chronic alcohol suppressed hepatic mRNA expression and activities of antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase; however, they were reversed by scopoletin supplementation, which reduced hydrogen peroxide and lipid peroxide levels in the liver. These results indicate that dietary scopoletin attenuated chronic alcohol-induced insulin resistance and activated the antioxidant defense system through regulation of hepatic gene expression in glucose and antioxidant metabolism.

The Effect of Puerariae thubergiana Bentham Extract on Brain Tissue in Alcohol-Treated Rats (칡추출물이 알코올을 급여한 흰쥐의 뇌조직에 미치는 영향)

  • 김명주;조수열
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.29 no.4
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    • pp.669-675
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    • 2000
  • This study investigated the effect of Puerariae Flos (PF; flower of Puerariae plant) and Puerariae Radix (PR; root of Puerariae plant) water extracts on the activities on the activities of ethanol-metabolizing enzymes and free radical generating/scavenging enzymes of brain in ethanol-treated rats. Five groups of male Sprague-Dawley rats were orally administered ethanol (25%, v/v) 5 g/kg body weight/day, and sacrificed 5 weeks post treatment. PF and PR water extracts were supplemented in a diet based on 1.2g (I) or 2.4 g (II) raw PF or PR/kg body weight/day. Alcohol dehydrogenase activity of brain was significantly lowered in PF of PR groups, whereas aldehyde dehydrogenase activity was significantly higher in PR groups than those of control and PF groups. Cytochrome P-450 content, aminopyrine D-methylase and aniline hydroxylase activities were decreased in both PF and PR groups compared to control group. Aldehyde oxidase and xanthine oxidase activities tended to decrease by Puerariae plant extract supplemented goups and degree of decrease predominated in PRI. Superoxide dismutase and glutathione S-transferase activities were increased in PF or PR groups, whereas glutathione peroxidase and catalase activities were significantly decrased by Puerariae plant extracts supplement. These results indicated that supplementation of PF or PR lowers free radical generating enzymes activities. It was suggested that the activities of ethanol metabolizing emzymes and antioxidant enzymes in brain can be enhanced by PF or PR supplement in ethanol-treated rats.

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Preventive Effects of Lycopene-Enriched Tomato Wine against Oxidative Stress in High Fat Diet-Fed Rats

  • Kim, A-Young;Jeon, Seon-Min;Jeong, Yong-Jin;Park, Yong-Bok;Jung, Un-Ju;Choi, Myung-Sook
    • Preventive Nutrition and Food Science
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    • v.16 no.2
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    • pp.95-103
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    • 2011
  • This study was performed to investigate the antioxidant mechanism of tomato wine with varying lycopene content in rats fed a high fat diet (HFD). Male Sprague-Dawley rats were randomly divided into five groups (n=10 per group) and fed an HFD (35% of total energy from fat) plus ethanol (7.2% of total energy from alcohol), tomato wine with varying lycopene content (0.425 mg%, 1.140 mg% or 2.045 mg% lycopene) or an isocaloric control diet for 6 weeks. Mice fed HFD plus ethanol significantly increased erythrocyte hydrogen peroxide and thiobarbituric acid reactive substances (TBARS) levels with increases in activities of erythrocyte antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and glutathione reductase (GR) compared to pair-fed rats. Supplementation of tomato wine with varying lycopene content decreased ethanol-mediated increases of erythrocyte lipid peroxidation and antioxidant enzyme activities in HFD-fed rats, and tomato wine with higher lycopene appeared to be more effective. Tomato wine also dose-dependently lowered TBARS levels with decreased pro-oxidant enzyme, xanthine oxidase (XOD) activity in plasma of HFD-fed rats. In contrast to erythrocytes, the inhibitory effects of tomato wine on hepatic lipid peroxidation were linked to increased hepatic antioxidant enzymes (SOD and CAT) and alcohol metabolizing enzyme (alcohol dehydrogenase and aldehyde dehydrogenase) activities. There were no significant differences in hepatic XOD and cytochrome P450-2E1 activities among the groups. Together, our data suggest that tomato wine fortified with lycopene has the potential to protect against ethanol-induced oxidative stress via regulation of antioxidant or pro-oxidant enzymes and alcohol metabolizing enzyme activities in plasma, erythrocyte and liver.

Effect of Monascus Pigment Extract on the Alcohol Metabolism in Rats (흰쥐에 있어서 홍국 색소 추출물이 알코올대사에 미치는 영향)

  • 유대식;최혜정;윤종국
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.32 no.4
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    • pp.603-607
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    • 2003
  • To investigate the alcohol metabolizing system in liver of rats drunken 10% ethanol with Monascus pigment extract (MPE), Sprague-Dawley male rats weighing about 250 g have been drunken 10% ethanol containing 1, 2.5 and 5% Monascus pigment extract for a month. Three groups of rats drunken 10% ethanol with MPE gained somewhat less body weight than normal group, but the changes of body weight was not significantly different among the former groups. All groups drunken MPE supplemented alcohol had no remarkable changes in liver function on the basis of liver weight/body weight, the serum levels of alanine aminotransferase and xanthine oxidase activity. 10% alcohol drunken animals (control group) showed significantly increased activity of hepatic alcohol dehydrogenase (ADH) by 87% compared with normal group and the animals drunken 1%, 2.5% and 5% MPE showed respectively 34%, 29% and 21% increased activity of hepatic ADH, whileas Km value of ADH in 1, 2.5 and 5% MPE group decreased by 40%, 30% and 19% respectively compared with the control, but Vmax showed no significant changes among MPE groups. In case of aldehyde dehydrogenase (ALDH), 1% MPE group showed significantly increased activity by 32% and 2.5% or 5% MPE group showed increasing tendency compared with control, and Km value in three experimental groups declined by 27% and no particular changes were found among those. Furthermore, Vmax value in 1, 2.5 and 5% MEP group increased by 88,56 and 22% respectively with the control. In the aspect of the area under the curve of a ethanol concentration versus time (AUC) profile obtained after administration of 10% alcohol with 1 or 5% MPE, the decreasing rate of AUC to the control was 18% in 1% MPE treated rats whereas 10% in 5% MPE group.

Effect of Semisulcospira libertina Extracts from Different Extraction Processes on Liver Cell Toxicity and Ethanol Metabolism (간세포 독성과 에탄올 대사에서 추출 조건에 따른 다슬기 추출물의 효과)

  • Cho, Kyoung Hwan;Choo, Ho Jin;Seo, Min Gyun;Kim, Jong Cheol;Shin, Yu Jin;Ryu, Gi Hyung;Cho, Hee Young;Jeong, Chi-Young;Hah, Young-Sool
    • Food Engineering Progress
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    • v.21 no.2
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    • pp.158-166
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    • 2017
  • Although Semisulcospira libertina is generally regarded as a supplement for the alleviation of alcohol hangover, little is known about its effects on cell metabolism. Therefore, this study was conducted to analyze the constituents of the extracts prepared using different extraction methods and to compare their biochemical properties. The amino acid contents were found to be much higher in acidic and enzymatic hydrolysates than hot water extracts from S. libertina. DPPH radical scavenging activities in acidic and enzymatic hydrolysates were higher than those of hot water extracts. Three types of S. libertina hydrolysate was added to HepG2 cells damaged by acetaminophen (AAP), after which the survival rate of HepG2 cell were measured. In addition, lactate dehydrogenase (LDH) activities in the culture media were evaluated. The survival rates of HepG2 cells were $77.0{\pm}4.3%$ and $81.5{\pm}1.3%$ at 3 h and 5h enzymatic hydrolysates, respectively. These cell survival rates were higher compared to those of the negative control group ($67.8{\pm}4.3%$) treated only with acetaminophen. Cellular toxicities induced by treatment with AAP were also significantly alleviated in response to treatment with the extracts of S. libertina. In addition, the activities of 2 key enzymes that metabolize ethanol, alcohol dehydrogenase and aldehyde dehydrogenase, were upregulated by 4.7- and 2.7-fold respectively in response to treatment with a 3 h enzymatic hydrolysate of S. libertina. Taken together, these results provide biochemical evidence of the method by which S. libertina exerts its biological functions, including the alleviation of alcohol hangover and the protection of liver cells against toxic insults.

Fermented Aloe arborescens Miller Leaf Extract Suppresses Acute Alcoholic Liver Injury via Antioxidant and Anti-Inflammatory Effects in C57BL/6J Mice

  • Min Ju Kim;Joon Hurh;Ha-Rim Kim;Sang-Wang Lee;Hong-Sig Sin;Sang-Jun Kim;Eun-mi Noh;Boung-Jun Oh;Seon-Young Kim
    • Journal of Microbiology and Biotechnology
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    • v.33 no.4
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    • pp.463-470
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    • 2023
  • This study confirmed the change in functional composition and alcohol-induced acute liver injury in Aloe arborescens after fermentation. An acute liver injury was induced by administration of ethanol (3 g/kg/day) to C57BL/6J mice for 5 days. A fermented A. arborescens Miller leaf (FAAL) extract was orally administered 30 minutes before ethanol treatment. After fermentation, the emodin content was approximately 13 times higher than that of the raw material. FAAL extract significantly attenuated ethanol-induced aspartate aminotransferase, alanine aminotransferase, and triglyceride increases in serum and liver tissue. Histological analysis revealed that FAAL extract inhibits inflammatory cell infiltration and fat accumulation in liver tissues. The cytochrome P450 2E1, superoxide dismutase, and glutathione (GSH), which involved in alcohol-induced oxidative stress, were effectively regulated by FAAL extract in serum and liver tissues, except for GSH. FAAL also maintained the antioxidant defense system by upregulating heme oxygenase 1 and nuclear factor erythroid 2-related factor 2 protein expression. In addition, FAAL extract inhibited the decrease in alcohol dehydrogenase and aldehyde dehydrogenase activity, which promoted alcohol metabolism and prevented the activation of inflammatory response. Our results suggest that FAAL could be used as a potential therapeutic agent for ethanol-induced acute liver injury.