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Journal of Food Science and Technology Dec 2022This study aimed to investigate the effect of mixture of herbal extracts and supplementary formula (FNP-C) on hangovers and antioxidant enzymes in alcohol-induced liver...
This study aimed to investigate the effect of mixture of herbal extracts and supplementary formula (FNP-C) on hangovers and antioxidant enzymes in alcohol-induced liver damage in rats. HepG2 cells were used as the experimental cells and divided into five groups: non-treated control (normal), alcohol-induced control (control), mixture of herbal extracts (FNP-B), FNP-C, and a commercial treatment of liver diseases (Livers); inhibition of detoxification and alcohol-induced damage was confirmed in vivo. Blood alcohol and acetaldehyde concentration after alcohol consumption were measured in a timely manner; alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), superoxide dismutase (SOD), glutathione (GSH), glutathione transferase (GST), and lactate dehydrogenase (LDH) levels were measured in the liver. FNP-C exhibited the highest effect. When FNP-C was administered to alcohol-induced animals, blood alcohol and acetaldehyde concentration decreased compared to FNP-B and Livers. FNP-C reduced ADH levels and improved LDH, GSH, GST, and SOD levels. The FNP-C group was effective in preventing alcohol-induced hangovers and liver damage. Thus, FNP-C improves hangovers and increases antioxidant activity in an alcohol-induced model. Adding amino acids and vitamins to natural ingredients can potentially enhance the effect of improving hangovers.
PubMed: 36276534
DOI: 10.1007/s13197-022-05580-4 -
Physiological Research Dec 2020Dihydromyricetin (DHM) is a natural flavonoid showing several health promoting effects such as protective activity during severe alcohol intoxication. The mechanism...
Dihydromyricetin (DHM) is a natural flavonoid showing several health promoting effects such as protective activity during severe alcohol intoxication. The mechanism underlying the effects of DHM on alcohol metabolism is virtually unknown. The present paper is focused on clarifying the role of DHM in the liver alcohol elimination at its molecular level. First, impact of DHM on alcohol dehydrogenase (ADH) activity in vitro and the enzyme induction in vivo was examined. Neither the ADH activity nor the enzyme expression were influenced by DHM. Next, the effect of DHM during alcohol intoxication were studied on primary hepatocytes isolated from EtOH-premedicated and untreated rats. The viability of cells exposed to alcohol, estimated based on the released enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), was slightly affected by DHM. Although the expected hepatoprotective effect of DHM was not fully achieved, DHM (in a concentration manner) proved to reduce the level of ROS/RNS in hepatocytes. However, no change in the rate of alcohol metabolism in vivo was found when rats were administered with a single or repeated dose of ethanol supplemented with DHM. In conclusion, the proposed positive effect of DHM during alcohol intoxication has not been proven. Moreover, there is no effect of DHM on the alcohol metabolism. The "hoped-for" DHM hepatoprotective activity can be attributed to the reduction of ROS/RNS levels in cells.
Topics: Alcohol Dehydrogenase; Animals; Antioxidants; Cells, Cultured; Cytochrome P-450 CYP2E1; Ethanol; Flavonols; Hepatocytes; Inactivation, Metabolic; Liver; Male; Nitrosative Stress; Oxidative Stress; Rats, Wistar; Reactive Nitrogen Species; Reactive Oxygen Species
PubMed: 33656905
DOI: 10.33549/physiolres.934606 -
Biomolecules Aug 2021Alcoholism is a complex behavior trait influenced by multiple genes as well as by sociocultural factors. Alcohol metabolism is one of the biological determinants that...
Alcoholism is a complex behavior trait influenced by multiple genes as well as by sociocultural factors. Alcohol metabolism is one of the biological determinants that can significantly influence drinking behaviors. Alcohol sensitivity is thought to be a behavioral trait marker for susceptibility to develop alcoholism. The subjective perceptions would be an indicator for the alcohol preference. To investigate alcohol sensitivity for the variants and , sixty healthy young males with different combinatory and genotypes, ( = 23), ( = 27), and ( = 10), participated in the study. The subjective perceptions were assessed by a structured scale, and blood ethanol and acetaldehyde were determined by GC and HPLC after an alcohol challenge in two dose sessions (0.3 g/kg or 0.5 g/kg ethanol). The principal findings are (1) dose-dependent increase of blood ethanol concentration, unaffected by or ; (2) significant build-up of blood acetaldehyde, strikingly influenced by the gene allele and correlated with the dose of ingested alcohol; (3) the increased heart rate and subjective sensations caused by acetaldehyde accumulation in the heterozygotes; (4) no significant effect of polymorphism in alcohol metabolism or producing the psychological responses. The study findings provide the evidence of acetaldehyde potentiating the alcohol sensitivity and feedback to self-control the drinking amount. The results indicate that plays a major role for acetaldehyde-related physiological negative responses and prove the genetic protection against development of alcoholism in East Asians.
Topics: Acetaldehyde; Adult; Alcohol Dehydrogenase; Alcohol Drinking; Alcoholism; Aldehyde Dehydrogenase, Mitochondrial; Ethanol; Healthy Volunteers; Humans; Male; Polymorphism, Genetic; Young Adult
PubMed: 34439848
DOI: 10.3390/biom11081183 -
Cancer Research and Treatment Jul 2021Excessive alcohol consumption has been linked to an increased risk of colorectal cancer (CRC). We evaluated the association between alcohol-related genetic variants and...
PURPOSE
Excessive alcohol consumption has been linked to an increased risk of colorectal cancer (CRC). We evaluated the association between alcohol-related genetic variants and CRC risk.
MATERIALS AND METHODS
The study cohort consisted of 5,435 CRC cases and 3,553 population-based cancer-free controls. Genotype data were generated from germline DNA using the Infinium OncoArray-500K BeadChip in 2,535 cases and 2,287 controls and the Infinium Multi-Ethnic Global BeadChip in 2,900 cases and 1,266 controls. The associations between aldehyde dehydrogenase 2 (ALDH2) rs671 and alcohol dehydrogenase 1B (ADH1B) rs1229984 polymorphisms and CRC risk were assessed using multivariate logistic regression analyses.
RESULTS
Compared with the major homozygous ALDH2 genotype (GG), heterozygous or minor homozygous ALDH2 genotype (GA or AA, related to a low alcohol consumption) was significantly associated with a reduced risk for CRC in men (odds ratio [OR], 0.78; 95% confidence interval [CI], 0.68 to 0.90), but not in women (OR, 0.70; 95% CI, 0.47 to 1.05). A stronger association was found among regular drinkers (OR, 0.58; 95% CI, 0.47 to 0.71 in men and OR, 0.33; 95% CI, 0.18 to 0.58 in women). No association of CRC risk with ADH1B rs1229984 genotype was found. The association between alcohol-related combined genotypes and risk of CRC was significant (p for linear=0.001). The combined genotype with the highest genetically predicted alcohol consumption (ALDH2 rs671 GG and ADH1B rs1229984 AG/GG) was associated with a high risk for CRC (OR, 1.35; 95% CI, 1.11 to 1.63).
CONCLUSION
Our study provides strong evidence for a possible causal association between alcohol consumption and CRC risk.
Topics: Aged; Alcohol Dehydrogenase; Alcohol Drinking; Aldehyde Dehydrogenase, Mitochondrial; Asian People; Case-Control Studies; Causality; Cohort Studies; Colorectal Neoplasms; Ethanol; Female; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Odds Ratio; Polymorphism, Single Nucleotide; Republic of Korea; Risk Assessment; Risk Factors
PubMed: 33421985
DOI: 10.4143/crt.2020.478 -
Nature Jan 2018Haematopoietic stem cells renew blood. Accumulation of DNA damage in these cells promotes their decline, while misrepair of this damage initiates malignancies. Here we...
Haematopoietic stem cells renew blood. Accumulation of DNA damage in these cells promotes their decline, while misrepair of this damage initiates malignancies. Here we describe the features and mutational landscape of DNA damage caused by acetaldehyde, an endogenous and alcohol-derived metabolite. This damage results in DNA double-stranded breaks that, despite stimulating recombination repair, also cause chromosome rearrangements. We combined transplantation of single haematopoietic stem cells with whole-genome sequencing to show that this damage occurs in stem cells, leading to deletions and rearrangements that are indicative of microhomology-mediated end-joining repair. Moreover, deletion of p53 completely rescues the survival of aldehyde-stressed and mutated haematopoietic stem cells, but does not change the pattern or the intensity of genome instability within individual stem cells. These findings characterize the mutation of the stem-cell genome by an alcohol-derived and endogenous source of DNA damage. Furthermore, we identify how the choice of DNA-repair pathway and a stringent p53 response limit the transmission of aldehyde-induced mutations in stem cells.
Topics: Acetaldehyde; Alcohol Dehydrogenase; Animals; Cell Survival; DNA Breaks, Double-Stranded; DNA End-Joining Repair; Ethanol; Fanconi Anemia; Fanconi Anemia Complementation Group D2 Protein; Female; Gene Deletion; Genes, p53; Genomic Instability; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Ku Autoantigen; Male; Mice; Mice, Inbred C57BL; Mutation; Recombinational DNA Repair; Tumor Suppressor Protein p53; Whole Genome Sequencing
PubMed: 29323295
DOI: 10.1038/nature25154 -
Nature Communications Apr 2023Biocatalysis is increasingly replacing traditional methods of manufacturing fine chemicals due to its green, mild, and highly selective nature, but biocatalysts, such as...
Biocatalysis is increasingly replacing traditional methods of manufacturing fine chemicals due to its green, mild, and highly selective nature, but biocatalysts, such as enzymes, are generally costly, fragile, and difficult to recycle. Immobilization provides protection for the enzyme and enables its convenient reuse, which makes immobilized enzymes promising heterogeneous biocatalysts; however, their industrial applications are limited by the low specific activity and poor stability. Herein, we report a feasible strategy utilizing the synergistic bridging of triazoles and metal ions to induce the formation of porous enzyme-assembled hydrogels with increased activity. The catalytic efficiency of the prepared enzyme-assembled hydrogels toward acetophenone reduction is 6.3 times higher than that of the free enzyme, and the reusability is confirmed by the high residual catalytic activity after 12 cycles of use. A near-atomic resolution (2.1 Å) structure of the hydrogel enzyme is successfully analyzed via cryogenic electron microscopy, which indicates a structure-property relationship for the enhanced performance. In addition, the possible mechanism of gel formation is elucidated, revealing the indispensability of triazoles and metal ions, which guides the use of two other enzymes to prepare enzyme-assembled hydrogels capable of good reusability. The described strategy can pave the way for the development of practical catalytic biomaterials and immobilized biocatalysts.
Topics: Hydrogels; Alcohol Dehydrogenase; Triazoles; Enzymes, Immobilized; Ions; Biocompatible Materials; Biocatalysis; Enzyme Stability
PubMed: 37055470
DOI: 10.1038/s41467-023-37921-y -
Angewandte Chemie (International Ed. in... Sep 2018Alcohol dehydrogenases can act as powerful catalysts in the preparation of optically pure γ-hydroxy-δ-lactones by means of an enantioconvergent dynamic redox...
Alcohol dehydrogenases can act as powerful catalysts in the preparation of optically pure γ-hydroxy-δ-lactones by means of an enantioconvergent dynamic redox isomerization of readily available Achmatowicz-type pyranones. Imitating the traditionally metal-mediated "borrowing hydrogen" approach to shuffle hydrides across molecular architectures and interconvert functional groups, this chemoinspired and purely biocatalytic interpretation effectively expands the enzymatic toolbox and provides new opportunities in the assembly of multienzyme cascades and tailor-made cellular factories.
Topics: Alcohol Dehydrogenase; Biocatalysis; Escherichia coli; Hydrogen; Isomerism; Lactones; Oxidation-Reduction; Oxidoreductases; Recombinant Proteins; Stereoisomerism
PubMed: 29984878
DOI: 10.1002/anie.201804911 -
Alcoholism, Clinical and Experimental... Oct 2021Studies investigating the effects of prenatal alcohol exposure on childhood attention-deficit hyperactivity disorder (ADHD) symptoms using conventional observational...
BACKGROUND
Studies investigating the effects of prenatal alcohol exposure on childhood attention-deficit hyperactivity disorder (ADHD) symptoms using conventional observational designs have reported inconsistent findings, which may be affected by unmeasured confounding and maternal and fetal ability to metabolize alcohol. We used genetic variants from the alcohol metabolizing genes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), as proxies for fetal alcohol exposure to investigate their association with risk of offspring ADHD symptoms around age 7-8 years.
METHODS
We used data from 3 longitudinal pregnancy cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC), Generation R study (GenR), and the Norwegian Mother, Father and Child Cohort study (MoBa). Genetic risk scores (GRS) for alcohol use and metabolism using 36 single nucleotide polymorphisms (SNPs) from ADH and ALDH genes were calculated for mothers (N = 8196; N = 13,614), fathers (N = 13,935), and offspring (N =8,237; N =14,112; N =2,661). Associations between maternal GRS and offspring risk of ADHD symptoms were tested in the full sample to avoid collider bias. Offspring GRS analyses were stratified by maternal drinking status.
RESULTS
The pooled estimate in maternal GRS analyses adjusted for offspring GRS in ALSPAC and MoBa was OR = 0.99, 95%CI 0.97-1.02. The pooled estimate in offspring GRS analyses stratified by maternal drinking status across all the cohorts was as follows: OR = 0.98, 95% CI 0.94-1.02; OR = 0.99, 95% CI 0.97-1.02. These findings remained similar after accounting for maternal genotype data in ALSPAC and maternal and paternal genotype data in MoBa.
CONCLUSIONS
We did not find evidence for a causal effect of fetal alcohol exposure on risk of ADHD symptoms in offspring. The results may be affected by limited power to detect small effects and outcome assessment.
Topics: Adult; Alcohol Dehydrogenase; Alcohol Drinking; Aldehyde Dehydrogenase; Attention Deficit Disorder with Hyperactivity; Child; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Gestational Age; Humans; Longitudinal Studies; Polymorphism, Single Nucleotide; Pregnancy; Prenatal Exposure Delayed Effects; Prospective Studies
PubMed: 34486127
DOI: 10.1111/acer.14692 -
Biochemistry and Molecular Biology... Jan 2022Project-based (research-driven) laboratory courses stimulate student involvement, improve critical thinking and initiate cooperative learning. To this end, a 7-week...
Project-based (research-driven) laboratory courses stimulate student involvement, improve critical thinking and initiate cooperative learning. To this end, a 7-week laboratory project was designed for a sophomore cell biology course to reinforce the fundamental relationship between genotype and phenotype using yeast alcohol dehydrogenase I (ADH1). Working in pairs, students used site-directed mutagenesis to create a H44R mutation in the ADH1 gene sequence inserted into a YEp13 shuttle vector. These plasmids were propagated in E. coli, sequenced, and reintroduced into a yeast strain expressing no ADH1 activity. The growth patterns on selective media were determined. As the mutation allows for growth in the presence of allyl alcohol, students make the connection between DNA sequence and protein function. Student performance was assessed with pre- and post-tests, with improvement observed across all learning objectives. In addition to meeting the learning outcomes, 98% of the students thought that this experience allowed them to see how the scientific process can encompass multiple techniques to answer a single question. Eighty-four percent of the students thought that this experience was more engaging than other lab experiences they have had. Our multi-week laboratory examining the phenotypic changes in yeast alcohol metabolism successfully developed students' understanding of the scientific process, knowledge of molecular techniques and the relationship of gene sequence to protein function in an engaging manner.
Topics: Alcohol Dehydrogenase; Escherichia coli; Genotype; Humans; Phenotype; Proteins; Saccharomyces cerevisiae
PubMed: 34878214
DOI: 10.1002/bmb.21594 -
Molecules (Basel, Switzerland) Jul 2023A biomimetic mineralization method was used in the facile and rapid preparation of nanoflowers for immobilizing alcohol dehydrogenase (ADH). The method mainly uses ADH...
A biomimetic mineralization method was used in the facile and rapid preparation of nanoflowers for immobilizing alcohol dehydrogenase (ADH). The method mainly uses ADH as an organic component and zinc phosphate as an inorganic component to prepare flower-like ADH/Zn(PO) organic-inorganic hybrid nanoflowers (HNFs) with the high specific surface area through a self-assembly process. The synthesis conditions of the ADH HNFs were optimized and its morphology was characterized. Under the optimum enzymatic reaction conditions, the Michaelis-Menten constant () of ADH HNFs (β-NAD as substrate) was measured to be 3.54 mM, and the half-maximal inhibitory concentration (IC) of the positive control ranitidine (0.2-0.8 mM) was determined to be 0.49 mM. Subsequently, the inhibitory activity of natural medicine Pursh and nine small-molecule compounds on ADH was evaluated using ADH HNFs. The inhibition percentage of the aqueous extract of is 57.9%. The vanillic acid, protocatechuic acid, gallic acid, and naringenin have obvious inhibitory effects on ADH, and their percentages of inhibition are 55.1%, 68.3%, 61.9%, and 75.5%, respectively. Moreover, molecular docking analysis was applied to explore the binding modes and sites of the four most active small-molecule compounds to ADH. The results of this study can broaden the application of immobilized enzymes through biomimetic mineralization, and provide a reference for the discovery of ADH inhibitors from natural products.
Topics: Alcohol Dehydrogenase; Nanostructures; Biomimetics; Molecular Docking Simulation
PubMed: 37513303
DOI: 10.3390/molecules28145429