• Title/Summary/Keyword: ALDH1A1

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Anti-Alcohol and Anti-Aldehyde Hangover Effect of Aldehyde Dehydrogenase Related Compounds in Rat (랫드에서 Aldehyde Dehydrogenase Related Compounds의 알콜 및 알데히드 분해 효능평가)

  • Hye-Jeong Sin;Se-Young Choung;Sora Kang;Hung-Taeck Kwon;Bae-Hwan Kim
    • Journal of Environmental Health Sciences
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    • v.49 no.2
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    • pp.99-107
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    • 2023
  • Background: Excessive alcohol consumption is at the root of serious social problems such as hangovers, liver dysfunction, and alcoholism. Objectives: This study was carried out to determine the hangover ameliorating effect of fermented rice extract and a combination of yeast-fermented powder and lysate containing aldehyde dehydrogenase (ALDH) (improved new ingredients) in an ethanol-induced rat study. Methods: The concentrations of alcohol, acetaldehyde, and malondialdehye in serum were evaluated to assess the anti-alcohol and anti-aldehyde hangover effect in two experiments, one with fermented rice extract) and a second with yeast-fermented powder and lysate, using animal studies. Results: Experiment 2 with yeast-fermented powder and lysate containing ALDH showed similar and higher activity, respectively, in reducing ethanol and acetaldehyde concentration compared with Experiment 1 with fermented rice extract. Experiment 2 also significantly reduced malondialdehyde, a type of lipid peroxide. The ALDH-related compound (ARC) lysate showed better hangover relief effect than ARC powder. Conclusions: These results indicate that ALDH-related compounds exhibit a hangover relief effect, and fermented lysate is considered to be a better candidate for hangover relief.

Purification of Mitochondrial Matrix Aldehyde Dehydrogenase from Pig Brain

  • Kim, Kyu-Tae;Lee, Young-Don
    • BMB Reports
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    • v.28 no.2
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    • pp.177-183
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    • 1995
  • The activity of aldehyde dehydrogenase (ALDH) in the cerebrum, cerebellum, striatum, and medulla oblongata was examined and mitochondrial matrix ALDH was purified prior to immunohistochemical study on the localization of ALDH isozymes in pig brain. Relatively high enzyme activity was found in the striatum and medulla oblongata when using indole-3-acetaldehyde as substrate, and in the striatum when using 3,4-dihydroxyphenylacetaldehyde (DOPAL). The main part of mitochondrial ALDH activities with both acetaldehyde and DOPAL existed in the matrix fraction. The ratio of activity of the matrix to the membrane fraction in the cerebrum was higher than in the cerebellum, suggesting that the distribution pattern of ALDH isozymes was different according to the brain regions. The 276-fold purified mitochondrial matrix ALDH from pig brain was identified to be homologous tetramers with 53 KD subunits. The enzyme showed maximal activity at pH 9.0 and was stable in the temperature range from $25^{\circ}C$ to $37^{\circ}C$. The mitochondrial matrix ALDH activity was considerably inhibited by acetaldehyde in vitro. The $K_m$ values of the enzyme for acetaldehyde and propionaldehyde were 5.8 mM and 4.9 mM, respectively, whereas $K_m$ values for indole-3-acetaldehyde and DOPAL were 44 ${\mu}M$ and 1.6 ${\mu}M$, respectively. The $V_{max}/K_{m}$ ratio was the highest with DOPAL as compared with other substrates. These results suggested that mitochondrial matrix ALDH in the present work might be a low Km isozyme involved in biogenic aldehyde oxidation in pig brain.

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Effects of Alcohol on Psychomotor Performance and Subjective Assessments In Normal Adults with Variation of Acetaldehyde Dehydrogenase I (정상성인에서 ALDH-I의 변이가 알콜의 정신운동성 수행과 주관적 평가에 미치는 영향)

  • Yoon, Bo Hyun;Yoon, Jin Sang
    • Korean Journal of Biological Psychiatry
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    • v.3 no.2
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    • pp.222-239
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    • 1996
  • The purpose of this study was to evaluate the effects of alcohol on the psychomotor performance and subjective assessment in healthy Korean adults with acetaldehyde dehydrogenase I(ALDH-I) isozyme variance. A total of 20 male subjects, half with active ALDH-I and the other half with inactive ALDH-I, were selected through both a self-reporting questionnaire examining alcohol sensitivity and the Higuchi's ethanol patch test detecting ALDH-I deficiency. In a doule-blind, placebo-controlled cross-over design, each subject consumed four doses of alcohol(0.25, 0.5, 0.75, 1.0g/kg) and placebo on five separate occasions at weekly intervals, Treatment order was fully balanced using a $5{\times}5$ Latin square, Psychomotor performance tests[coritical flicker fusion threshold(CFF) and choice reaction time(CRT)] and self-estimate questionnaires were conducted at baseline and at time points of 20, 40, 60, 90, 120, 150, 180 minutes after consuming the test drug for 20 minutes, Blood alcohol concentrations(BACs) using breath analyzer were measured at baseline and at time points of 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150, 180 minutes after drinking, The BACs and the mean changes in the psychomotor performances and subjective assessments from pre-alcohol baseline, were compared between the two groups. The findings were summarized as follows : 1) BACs were tended to be higher in the inactive group than the active in all of the four alcohol doses. However significant group differences were only after the 0.5g/kg dose of alcohol. 2) The inactive group showed significant impairment in CFFT at most time points alter 0.75 and 1.0g/kg doses of alcohol. 3) In CRT, total reaction time(TRT) significantly prolonged in the inactive group than the active group at 20 minutes after 0.25 and 1.0g/kg doses of alcohol and at 40, 60, 90 minutes alter 0.75g/kg dose of alcohol. In the inactive group, recognition time component significantly increased at 20, 60, 90 minutes after 1.0g/kg dose of alcohol, while movement time component significantly increased at 40, 60 minutes after 0.75g/kg dose of alcohol. 4) Subjective evaluation of the effect of alcohol revealed that physical and mental conditions as well as a self-estimate of the effects of alcohol on performance were significantly worse in the inactive group than the active at some time points alter all of the lour alcohol doses, wihch were more pronounced after 0.75 and 1.0g/kg doses of alcohol. 5) Most of the group differences mentioned above, still remained statistically significant after BAC was entered as a covariate, These findings demonstrated that the alcohol sensitivity is higher in individuals with inactive ALDH-I than those with active ALDH-I both on the subjective assessments and the objective psychomotor performances. Furthermore, these results suggest thai the alcohol sensitivity may be determined by acetaldehyde concentration rather than BAC per se. In future studies, after more accurate genotyping for ALDH-I, the relationships between BAC, acetaldehyde concentration and alcohol sensitivities should be clearly defined.

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p63 Cytoplasmic Aberrance is Associated with High Prostate Cancer Stem Cell Expression

  • Ferronika, Paranita;Triningsih, F.X. Ediati;Ghozali, Ahmad;Moeljono, Abraham;Rahmayanti, Siti;Shadrina, Arifah Nur;Naim, Awang Emir;Wudexi, Ivan;Arnurisa, Alfa Monica;Nanwani, Sandeep Tarman;Harijadi, Ahmad
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.5
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    • pp.1943-1948
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    • 2012
  • Introduction: Prostate cancer in Indonesia is the $3^{rd}$ ranking cancer among males and the $5^{th}$ rank for their cancer mortality. Prognostic markers that can identify aggressive prostate cancer in early stages and help select appropriate therapy to finally reduce the mortality are therefore urgently needed. It has been suggested that stem cells in the prostate gland have a role in initiation, progression, and metastasis of cancer, although controversy continues to exist. Maintenance of normal stem cell or reserve cell populations in several epithelia including prostate has been shown to be regulated by p63 and alteration of p63 expression is considered to have an oncogenic role in prostate cancer. We hypothesize that the expression of cytoplasmic aberrance of p63 is associated with high ALDH1A1 expression as a cancer stem cell marker, thus leading to progression of prostate cancer. Methods: Using a cross-sectional study during two years (2009-2010), a total of 79 paraffin embedded tissues of benign prostatic hyperplasia, PIN prostatic intraepithelial neoplasia, low and high Gleason score prostate cancer were investigated using immunohistochemistry. Associations between cytoplasmic p63 and ALDH1A1, as well as with pathological diagnosis, were analyzed by Chi-Square test using SPSS 15.0. Links of both markers with cell proliferation rate (KI-67) and apoptotic rate (cleaved caspase 3) were also analyzed by Kruskal-Wallis test. Results: The mean age of patient at the diagnosis is 70.0 years. Cytoplasmic aberrance of p63 was associated with ALDH1A1 expression (p<0.001) and both were found to have significant relationships with pathological diagnosis (including Gleason score), (p=0.006 and p<0.001 respectively). Moreover, it was also found that higher levels of cytoplasmic p63 were significantly associated with the frequency of proliferating cells and cells undergoing apoptosis in prostate cancers (p=0.001 and p=0.016 respectively). Conclusion: p63 cytoplasmic aberrance is associated with high ALDH1A1 expression. These components are suggested to have an important role in prostate cancer progression and may be used as molecular markers.

Effects of Alcohol Intake, Genotypes of Aldehyde Dehydrogenase 2 and N-Acetyltransferase 2 on the Development of Laryngeal Cancer in Koreans (한국인의 후두암 발생에서 음주, Aldehyde Dehydrogenase 2(ALDH2)와 N-Acetyltransferase 2(NAT2) 유전자 다형성의 역할)

  • Kwon Soon-Uk;Shim Yoon-Sang;Lee Yong-Sik;Hong Seong-Chool;Kim Kwang-Il;Hong Young-Joon;Hong Seok-Il;Kim Hyun-Joo;Kim Heon;Lee Guk-Haeng
    • Korean Journal of Head & Neck Oncology
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    • v.17 no.2
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    • pp.131-138
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    • 2001
  • Objectives: Alcohol intake has been reported to be a risk factor of laryngeal cancer. Since the aldehyde dehydrogenase 2 (ALDH2) genotype is a major determinant of personal alcohol drinking habit, there is a possibility that ALDH2 genotype would be a risk factor for laryngeal cancer. N-Acetyltransferase 2 (NAT2) is a detoxifying enzyme and its polymorphism has been reported to be related to the risk of many environmental cancers. However, studies on the associations between these two genotypes and laryngeal cancer risk are scarce. We have assessed the effects of alcohol intake and the genotype of ALDH2 and NAT2 on the risk of laryngeal cancer in Koreans. Materials and Methods: Eighty-four pathologically proven laryngeal cancer patients and 168 age matched controls were included as the study subjects. Information about alcohol intake and smoking habit was collected using a self administered questionnaire. ALDH2 and NAT2 genotypes were analyzed using PCR-RFLP methods. Results: Alcohol intake was significant as a risk factor for laryngeal cancer (OR : 2.58, 95% CI : 1.24, 5.36), especially for supraglottic laryngeal cancer (OR : 3.24, 95% CI : 1.02, 10.31). Personal drinking habit was closely related with personal smoking habit, which was a potent risk factor of laryngeal cancer. In a stratified analysis according to the level of cumulative smoking amount, drinking was significant neither in light smokers (equal or less than 30 pack-years) nor in heavy smoker (over 30 pack-years). The ALDH2 genotype was significantly associated with the risk of laryngeal cancer in a univariate analysis. The statistical significance, however, disappeared after adjusting alcohol intake using a multiple conditional logistic model. The NAT2 genotype was not significant as a risk factor for laryngeal cancer. Conclusion: Alcohol drinking and ALDH2 genotype would have indirect effects on laryngeal cancer by their correlations with cigarette smoking or with alcohol drinking. It is less likely that the NAT2 genotype would be a potent risk factor of laryngeal cancer.

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Gene Expression Profiles in Genetically Different Mice Infected with $Toxoplasma$ $gondii$: ALDH1A2, BEX2, EGR2, CCL3 and PLAU

  • Ismail, Hassan Ahmed Hassan Ahmed;Quan, Juan-Hua;Wei, Zhou;Choi, In-Wook;Cha, Guang-Ho;Shin, Dae-Whan;Lee, Young-Ha;Song, Chang-June
    • Parasites, Hosts and Diseases
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    • v.50 no.1
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    • pp.7-13
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    • 2012
  • $Toxoplasma$ $gondii$ can modulate host cell gene expression; however, determining gene expression levels in intermediate hosts after $T.$ $gondii$ infection is not known much. We selected 5 genes ($ALDH1A2$, $BEX2$, $CCL3$, $EGR2$ and $PLAU$) and compared the mRNA expression levels in the spleen, liver, lung and small intestine of genetically different mice infected with $T.$ $gondii$. ALDH1A2 mRNA expressions of both mouse strains were markedly increased at day 1-4 postinfection (PI) and then decreased, and its expressions in the spleen and lung were significantly higher in C57BL/6 mice than those of BALB/c mice. BEX2 and CCR3 mRNA expressions of both mouse strains were significantly increased from day 7 PI and peaked at day 15-30 PI ($P$<0.05), especially high in the spleen liver or small intestine of C57BL/6 mice. EGR2 and PLAU mRNA expressions of both mouse strains were significantly increased after infection, especially high in the spleen and liver. However, their expression patterns were varied depending on the tissue and mouse strain. Taken together, $T.$ $gondii$-susceptible C57BL/6 mice expressed higher levels of these 5 genes than did $T.$ $gondii$-resistant BALB/c mice, particularly in the spleen and liver. And ALDH1A2 and PLAU expressions were increased acutely, whereas BEX2, CCL3 and EGR2 expressions were increased lately. Thus, these demonstrate that host genetic factors exert a strong impact on the expression of these 5 genes and their expression patterns were varied depending on the gene or tissue.

Effect of Ginseng Saponin on Alcohol Metabolism in the Animal Body (인삼사포닌이 동물생체의 주정대사에 미치는 영향)

  • Joo, Chung-No
    • Journal of Ginseng Research
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    • v.16 no.3
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    • pp.222-227
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    • 1992
  • Unlike carbohydrats and fats, alcohol is essentially foreign to the body and it is known that the body get rid of it by oxidizing alcohol maily in the liver. Acetaldehyde is produced during ethanol metabolism and is known to be oxidized mainly by aldehyde dehydrogenase (ALDH). ALDH activity was found mainly in the mitochondrial fraction but a significant ALDH activity was also present in microsomal and cytosol fraction. Wistar rats (150~200 g, male) were given freely with 12% ethanol (Control) and/or 12% ethanol containing 0.1% ginseng saponins (Test) instead of water for 6 days and the liver was analyzed. ALDH activities of both control and test group were lower than that of normal group but test AkDH was less inhibited than control. ADH activies of both control and test were slightly higher than that of normal group but our previous data showed that it became gradually steady after prolonged ethanol feeding. MEOS activities of both control and test group were much higher than that of normal group. MEOS enzymes are inducible but the activity of test group was greatly higher than that of control. Ethanol containing [1-i4C] ethanol (5 $\mu$Ci) was injected to the above three groups and 30 min later, the distribution of radioactivity of hepatic lipids was investigated. Radioactivities of hepatic lipids of both control and test group were higher than that of normal group, however, that of test group was much lower than that of control. Analysis of individual lipids showed that phospholipid biosynthesis was significantly impaired and fatty acid and triglycerides biosynthesis were greatly stimulated. However, it was realized that the saponin prevented phospholipid biosynthesis depression and the increase of triglyceride biosynthesis considerably. It seemed that the saponin might stimulate ADH, ALDH and MEOS and the acetaldehyde formed would be removed faster. The excess hydrogen can be shunt more quickly into lipid biosynthesis. Electron microscopic observation showed that the hepatic cell of control group was si gnificantly damaged. Mitochondria were swollen and rough endoplasmic reticulum were dilated, however, hepatocytes of test group were not damaged.

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Effect of Black Red Ginseng Mixture on Alcohol Metabolism in Rats (흑홍삼혼합물이 체내 알코올대사에 미치는 효과)

  • Lee, Jun;Hwang, Byung Hwan;Song, Hye-Jin;Jang, Seon Hyeong;Choe, Soo Young
    • The Korean Journal of Food And Nutrition
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    • v.29 no.5
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    • pp.655-662
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    • 2016
  • Ginsenosides are major constituents of ginseng and are known to be responsible for its pharmacological properties. This study aimed to investigate the detoxification effect of a mixture containing black red ginseng powder, red ginseng extract, Puerariae radix extract, and Hovenia dulcis extract, on SD (Sprague Dawley) rats treated with 30% ethanol. Thirty minutes before treatment, the animals were orally administered different concentrations of the mixture or water. Results revealed that the concentration of ethanol in blood serum was significantly decreased in the black red ginseng mixture treated group in a dose-dependent manner, as compared with that of the control group. The blood level of acetaldehyde increased until 1 hr after alcohol administration, but the levels rapidly decreased later. Furthermore, ADH and ALDH activities in the hepatic tissue were also increased in the black red ginseng mixture administered group, than in the control group. These results indicate that the black red ginseng mixture has the ability of decomposing alcohol by increasing the ADH and ALDH activities responsible for alcohol metabolism.

Protective efficacies of Aronia melanocarpa (Blackberry) on the Allyl Alcohol-damaged Hepatocyte of Mice (쥐의 알코올성 간세포 손상에 대한 Aronia melanocapa(Blackberry)의 보호효과)

  • Han, Sang-Zin
    • Korean Journal of Pharmacognosy
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    • v.44 no.1
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    • pp.91-96
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    • 2013
  • The results of the alcohol decomposition ability of Aronia melanocarpa are as follows. Plasma alcohol concentration of the Aronia group was ca. 48.9% lower than the control group, but half an hour faster in that of Aronia before alcohol group, ca. 54.9% higher and half an hour later than that of the control group. ALDH(acetaldehyde dehydrogenase) of the Aronia group was ca. 243% higher than that of the control group. But maximal ALDH of the group taking Aronia before alcohol administration showed 0.5h faster and ca. 267% higher than that of the control group. This result shows that the activity of ALDH was increased by the Aronia. Aronia group's AST and ALT are increasing with similar patterns and their levels continually under the control's, but ca. 12.6% lower at AST and ca. 19.0% lower at ALT than those of control group. Ca. 21.7% lower at AST and ca. 40.5% lower at ALT in the Aronia group before alcohol administration than those of the control group. This result shows that Aronia has a role of suppressor against the liver damage. Therefore, this study proved lucidly the protective effects of Aronia on the hepatocyte.

Inhibition of Hepatic Triglyceride Accumulation and Stimulation of Alcohol Metabolism by the Herbal Extract Containing Phaseoli radiati semen in Rats Fed Ethanol (급성 알콜 투여 흰쥐에서 녹두 함유 복합생약제제의 간 중성지방 축적억제 및 알콜대사 촉진 효과)

  • Kim, Moon-Hee;Kwon, Oh-Hyep;Park, Chan-Koo
    • YAKHAK HOEJI
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    • v.40 no.1
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    • pp.78-83
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    • 1996
  • An ethanol administration causes hepatic triglyceride accumulation in rats. To assess whether the herbal extract containing Phaseoli radiati semen(herbal extract) inhibit s the triglyceride accumulation in the liver, we determined the hepatic triglyceiide levels in rats fed ethanol and the herbal extract. In addition, the blood ethanol concentrations and the activities of hepatic alcohol dehydrogenase(ADH) and aldehyde dehydrogenase(ALDH) were measured to determine the effects of the herbal extract on alcohol metabolism in rats. The administration of the herbal extract markedly reduced the triglyceride levels elevated by ethanol in the liver as well as in the serum. The herbal extract remarkably lowered blood ethanol concentrations in a dose-dependent manner. The ADH activities decreased by ethanol were recovered to the normal level by the herbal extract treatment. Moreover, the ALDH activities slightly decreased by ethanol increased beyond the normal level by the herbal extract treatment. We conclude that the herbal extract inhibits the hepatic triglyceride accumulation and stimulates alcohol metabolism by preventing ADH and ALDH from inhbition by the ethanol administration in the rat liver.

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