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Oxidative pathways of alcohol metabolism. Alcohol is metabolized mainly in the cytosol by alcohol dehydrogenase (ADH) to produce acetaldehyde. At high levels of alcohol consumption, an enzyme in the endoplasmic reticulum, cytochrome P450 IIE1 (CYP2E1), becomes involved in metabolizing alcohol to acetaldehyde; this enzyme also is induced by chronic drinking. A catalase-mediated reaction in the peroxisomes is considered a minor metabolic pathway of alcohol metabolism. Acetaldehyde is further metabolized to acetate in the mitochondria. Alcohol metabolism results in the formation of NADH and thus changes the redox state of hepatocytes (i.e., increases the ratio of NADH/NAD+). Both alcohol metabolism by CYP2E1 and the re-oxidation of NADH via the electron transport chain in the mitochondria results in the formation of reactive oxygen species (ROS).
Source publication
Metabolites, including those generated during ethanol metabolism, can impact disease states by binding to transcription factors and/or modifying chromatin structure, thereby altering gene expression patterns. For example, the activities of enzymes involved in epigenetic modifications such as DNA and histone methylation and histone acetylation, are...
Citations
... Interestingly, there is also evidence to suggest that methylation of LINE-1 and Alu elements may be sensitive to environmental exposures. Indeed, numerous CVD risk factors, including exposure to air pollution [69,70], cigarette smoking [71], and alcohol consumption [72], have also been associated with DNA hypomethylation, suggesting this epigenetic signature may be an early event in the development of CVDs, as well as other lifestyle-related diseases. ...
Non-communicable diseases (NCDs) are the leading cause of death worldwide, with cardiovascular disease (CVD) accounting for half of all NCD-related deaths. The biological onset of CVD may occur long before the development of clinical symptoms, hence the urgent need to understand the molecular alterations underpinning CVD, which would facilitate intervention strategies to prevent or delay the onset of the disease. There is evidence to suggest that CVD develops through a complex interplay between genetic, lifestyle, and environmental factors. Epigenetic modifications, including DNA methylation, serve as proxies linking genetics and the environment to phenotypes and diseases. In the past decade, a growing list of studies has implicated DNA methylation in the early events of CVD pathogenesis. In this regard, screening for these epigenetic marks in asymptomatic individuals may assist in the early detection of CVD and serve to predict the response to therapeutic interventions. This review discusses the current literature on the relationship between blood-based DNA methylation alterations and CVD in humans. We highlight a set of differentially methylated genes that show promise as candidates for diagnostic and prognostic CVD biomarkers, which should be prioritized and replicated in future studies across additional populations. Finally, we discuss key limitations in DNA methylation studies, including genetic diversity, interpatient variability, cellular heterogeneity, study confounders, different methodological approaches used to isolate and measure DNA methylation, sample sizes, and cross-sectional study design.
... Moreover, hepatic and neuronal tissue were stated to be influenced by the epigenetic of alcohol consumption [32]. It has been stated that methanol could lead to siteselective methylation, acetylation and phosphorylation of histones and DNA hypomethylation and result in reduction of S-adenosyl methionine (SAM) in tissue [32,33]. Kruman and Fowler have reported that alcohol's interference with one carbon metabolism (OCM) result in reduced availability of methyl groups and increased aberrant methylation of DNA and gene expression in alcoholic individuals [34]. ...
Objective:
The concept of "lifestyle" encompasses various factors, including nutrition, behavior, stress, physical activity, work habits, smoking, and alcohol consumption. Increasing evidence suggests that environmental and lifestyle factors can influence epigenetic mechanisms, such as DNA methylation, histone acetylation, and microRNA expression. Given that microRNAs (miRNAs) are an emerging focus in cancer research, there is growing interest in understanding how lifestyle choices affect miRNA responses. MiR-21 is well-established as an oncogenic miRNA, while miR-125a is reported as a tumor-suppressive miRNA in different cancers. This study aimed to analyze whether cigarette smoking and alcohol consumption are associated with altered levels of these salivary miRNAs in healthy individuals.
Methods:
Saliva supernatant samples from 50 healthy individuals (10% smokers and 34% alcohol drinkers) were analyzed alongside non-smokers and non-alcohol drinkers using real-time polymerase chain reaction (PCR). The expression levels of miR-21 and miR-125a were compared across samples based on demographic characteristics, social status, and smoking and drinking habits.
Result:
The data showed overexpression of salivary miR-21 in individuals who regularly consumed alcohol and smoked, while miR-125a expression was not significantly affected in either group.
Conclusion:
The differential expression of salivary miR-21 in healthy individuals from a localized population suggests a correlation with common lifestyle risk factors.
... Like other environmental and lifestyle factors [7,8], alcohol consumption is linked to the epigenome, specifically blood-based DNA methylation (DNAm) patterns [9][10][11]. DNAm is an epigenetic mark that is typically characterized by the addition of a methyl group to the 5' carbon of a cytosine base, often occurring at cytosinephosphate-guanine (CpG) dinucleotides, also referred to as a CpG site [12]. ...
Alcohol consumption is an important risk factor for multiple diseases. It is typically assessed via self-report, which is open to measurement error through recall bias. Instead, molecular data such as blood-based DNA methylation (DNAm) could be used to derive a more objective measure of alcohol consumption by incorporating information from cytosine-phosphate-guanine (CpG) sites known to be linked to the trait. Here, we explore the epigenetic architecture of self-reported weekly units of alcohol consumption in the Generation Scotland study. We first create a blood-based epigenetic score (EpiScore) of alcohol consumption using elastic net penalized linear regression. We explore the effect of pre-filtering for CpG features ahead of elastic net, as well as differential patterns by sex and by units consumed in the last week relative to an average week. The final EpiScore was trained on 16,717 individuals and tested in four external cohorts: the Lothian Birth Cohorts (LBC) of 1921 and 1936, the Sister Study, and the Avon Longitudinal Study of Parents and Children (total N across studies > 10,000). The maximum Pearson correlation between the EpiScore and self-reported alcohol consumption within cohort ranged from 0.41 to 0.53. In LBC1936, higher EpiScore levels had significant associations with poorer global brain imaging metrics, whereas self-reported alcohol consumption did not. Finally, we identified two novel CpG loci via a Bayesian penalized regression epigenome-wide association study of alcohol consumption. Together, these findings show how DNAm can objectively characterize patterns of alcohol consumption that associate with brain health, unlike self-reported estimates.
... By comparing the FT-Raman spectra of serum samples collected from alcohol-administered patients with those from control subjects, the researchers sought to elucidate distinct molecular signatures associated with alcohol consumption. Previous researches have indicated that alcohol consumption can perturb pathways and cause epigenetic modifications on DNA repair and cell cycle [9,10]. Thus, the biochemical composition of serum, leading to alterations in the vibrational spectra of key biomolecules such as proteins, lipids, and carbohydrates in different diseases [11][12][13]. ...
Alcohol is one of the most widely used stimulants globally, with increasing consumption rates annually. Prolonged alcohol consumption leads to significant physiological and neurological changes, potentially resulting in various diseases, which could be detect in serum. Therefore, FT-Raman spectroscopy was used to measure chemical changes in the serum of heavy drinkers, and these results were compared with the serum composition of a control group of non-drinkers. Obtained results showed a significant increase in lipids and a decrease in the amide/lipid ratio after alcohol administration. Additionally, higher amide III/amide II and lower amide II/amide I ratios were observed in the serum of alcohol-addicted patients. These shifts of 892, 966, 1286, 1459 and 2940 cm−1 peaks indicate alterations in the protein-lipid balance due to alcohol consumption. Principal component analysis (PCA) was employed to further analyze the spectral data, with the first three principal components accounting for 95.36% of total data variability. A Bayesian-optimized k-nearest neighbor (BO-KNN) model was applied for classification. The optimal hyperparameters—two neighbors, correlation distance metric, and squared inverse distance weight—were determined after seven iterations, resulting in a remarkably low classification error of 0.0384. The BO-KNN model achieved training and test accuracies of 95.92% and 90.48%, respectively. Receiver operating characteristic (ROC) analysis showed an area under the curve (AUC) of 1.00 for the training set and 0.90 for the test set, demonstrating the model's high precision and robustness. In conclusion, FT-Raman spectroscopy effectively revealed significant chemical changes in the serum of alcohol-addicted individuals, providing valuable insights into the biochemical impact of alcohol consumption.
... Ingested ethanol is metabolized in the body by alcohol dehydrogenase (ADH), catalase, or cytochrome P450 2E1 (CYP2E1) to acetaldehyde, which is then further oxidized by aldehyde dehydrogenase 2 (ALDH2) to acetate. This process generates reactive oxygen species (ROS) that may induce DNA damage [12]. Moreover, acetaldehyde leads to the formation of DNA adducts, thus inhibiting DNA repair systems and interfering with DNA replication. ...
Background
The incidence of alcohol‐associated cancers is higher within Asian populations having an increased prevalence of an inactivating mutation in aldehyde dehydrogenase 2 ( ALDH2 ), a mitochondrial enzyme required for the clearance of acetaldehyde, a cytotoxic metabolite of ethanol. The role of alcohol consumption in promoting lung cancer is controversial, and little attention has been paid to the association between alcohol drinking and pulmonary ALDH2 expression.
Methods
We performed a comprehensive bioinformatic analysis of multi‐omics data available in public databases to elucidate the role of ALDH2 in lung adenocarcinoma (LUAD).
Results
Transcriptional and proteomic data indicate a substantial pulmonary expression of ALDH2, which is functional for the metabolism of alcohol diffused from the bronchial circulation. ALDH2 expression is higher in healthy lung tissue than in LUAD and inhibits cell cycle, apoptosis, and epithelial–mesenchymal transition pathways. Moreover, low ALDH2 mRNA levels predict poor prognosis and low overall survival in LUAD patients. Interestingly, ALDH2 expression correlates with immune infiltration in LUAD.
Conclusions
A better understanding of the role of ALDH2 in lung tumor progression and immune infiltration might support its potential use as a prognostic marker and therapeutic target for improving immunotherapeutic response.
... These enzymes catalyze the transformation of alcohol into aldehyde or ketone with the concurrent reduction of nicotinamide adenine dinucleotide (NAD+) (Figure 1a). While this reaction yields potentially toxic intermediates, it also generates aldehyde and alcohol groups that serve various physiological functions [3]. ADH enzymes are particularly vital in yeasts, plants, and many bacterial species, where they drive fermentation processes critical for replenishing NAD+ (Figure 1b,c) and sustaining key metabolic pathways, thereby supporting survival and growth in low-oxygen environments [2,4]. ...
... In yeasts and bacteria, ADH enzymes-typically functioning as tetramers with two zinc ions per monomer-catalyze reactions crucial for energy production through the conversion of acetaldehyde to ethanol. These functions are particularly important under conditions of low oxygen or low temperatures, enabling these organisms to adapt to environmental stressors [2,3]. ADH enzymes in plants similarly contribute to the maintenance of cellular redox balance and NAD+ regeneration [4,5]. ...
Alcohol dehydrogenases (ADHs) are critical enzymes involved in the oxidation of alcohols, contributing to various metabolic pathways across organisms. This study investigates type I functional divergence within three ADH1 families: Saccharomyces cerevisiae (PDB ID: 4W6Z), Gadus morhua (PDB ID: 1CDO), and Homo sapiens (PDB ID: 1HDX). Understanding the molecular evolution and mechanisms underlying functional divergence of ADHs is essential for comprehending their adaptive significance. For this purpose, we performed a computational analysis that included structural characterization of ADHs through three-dimensional modeling, site-specific analysis to evaluate selective pressures and evolutionary constraints, and network analysis to elucidate relationships between structural features and functional divergence. Our findings indicate substantial variations in evolutionary and structural adaptations among the ADH families.
... lipid peroxidation has been suggested to be an important contributor to the induction of ethanol-mediated liver injury (Michalak et al., 2021). ethanol generates excess ROs production by causing suppression of homocysteine remethylation, depletion of naDPh and mitochondrial dysfunction (Zakhari, 2013). the production of excess ROs reacts with the lipid membrane and initiates lipid peroxidation, causing cell damage through oxidation of lipids and proteins (su et al., 2019). in the present study, the ethanol-treated group showed a significant increase in the levels of MDa, nOx, Oh and h 2 O 2 . ...
In our study, the antioxidant and anti-inflammatory effects of different lichen applications were investigated in rats using an experimental ethanol toxicity model. 48 rats were used in the study and they were divided into 6 groups with 8 rats in each group. These groups were: control, ethanol (2 g/kg), ethanol + Usnea longissima Ach. (200 mg/kg), ethanol + Usnea longissima Ach. (400 mg/kg), ethanol + Xanthoparmelia somloensis (Gyelnik) Hale (100 mg/kg) and ethanol + Xanthoparmelia somloensis (Gyelnik) Hale (200 mg/kg). The experimental work continued for 21 days. Lichen extracts and ethanol were administered by gavage to rats divided into groups. According to the experimental protocol, the experimental animals were sacrificed and their liver tissues were isolated. Biochemical parameters in serum, histological examinations, oxidative stress and inflammation parameters both at biochemical and molecular level in liver tissues were performed. Oxidative stress and inflammatory response were increased in the liver tissue of rats treated with ethanol for 21 days, and liver functions were impaired. It was found that U. longissima and X. somloensis extracts showed good antioxidant activity and conferred protective effects against ethanol-induced oxidative stress and inflammation. This could be attributed to the presence of secondary metabolites in the extract, which act as natural antioxidants and could be responsible for increasing the defence mechanisms against free radical production induced by ethanol administration.
... [32] The consumption of alcohol is often linked with the development of diseases and alcohol-induced oxidative stress. [33] The body increased production of the enzymes needed to carry electrons during metabolism, nicotinamide adenine dinucleotide, brought on by the metabolism of ethanol, causes an increase in respiration and oxygen consumption, which in turn causes an increase in oxidative stress and a decrease in CAT activity, [34] as shown in Table 1 above. ...
Background: Alcohol consumption has a negative effect on male fertility, but Vitamin C may be able to alleviate this effect. Aims: In this study, the protective effect of Vitamin C against alcohol-induced testicular damage in adult male Wistar rats was evaluated. Settings and Design: This study was conducted in a University setting. Following a 14-day acclimatisation period, forty adult male Wistar rats were randomly divided into eight groups of five rats. The control group received only food and water, test group B received alcohol only, test group C to E received different doses of Vitamin C, test group F to G received different doses of Vitamin C and alcohol. Materials and Methods: After a 21-day treatment period, the testis were harvested and analysed for sperm parameters, antioxidant enzyme activity, level of lipid peroxidation and histopathological changes. Statistical Analysis Used: All analyses was performed using SPSS (version 16) and Microsoft Excel (2019) using Student's t-test. Results: The results showed that in groups administered with alcohol only, there was a decrease in sperm count. Sperm motility, morphology, viability and antioxidant enzyme activity, but increase in the level of lipid peroxidation. In groups treated with Vitamin C and alcohol, there was improvement in the sperm parameters, antioxidant enzymes activity and a decrease and decrease in lipid peroxidation. Furthermore, in the histology of the testis, regenerative changes were seen. Conclusion: The chronic consumption of alcohol can have a deleterious effect on the testis, but commercial-grade Vitamin C can reverse these effects. Abstract This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms. For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com How to cite this article: George TE, Okhiai PO, Osonuga IO, Oyesola OA. Protective effect of commercial grade Vitamin C against alcohol-induced testicular damage in male Wistar rats. J Hum Reprod Sci 2023;16:99-105.
... 6 Alcohol metabolism is a complicated process (Fig. 1) and has been under study for many decades. 7 The prediction of BAC accurately following alcohol use remains a field of ongoing scientific inquiry. Precise BAC estimate at a given time point is complicated by individual variability of body characteristics and metabolism (e.g., age, body mass, liver health, feeding and hydration status, and basal metabolic rate) or alcohol concentration variability in the consumed drinks and the type of the biological samples used to estimate the alcohol level. ...
... Alcohol consumption can affect epigenetic modification and gene expression (40)(41)(42), and associated DNA methylation changes have been observed in both the peripheral and central nervous systems (43,44). Chronic alcohol consumption can trigger neuroinflammation resulting in central nervous system injury and possibly neurodegeneration (45)(46)(47)(48). ...
Introduction
Alcohol consumption can induce a neuroinflammatory response and contribute to the progression of neurodegeneration. However, its association with Parkinson’s disease (PD), the second most common neurodegenerative disorder, remains undetermined. Recent studies suggest that the glycoprotein non-metastatic melanoma protein B (GPNMB) is a potential biomarker for PD. We evaluated the association of rs199347, a variant of the GPNMB gene, with alcohol consumption and methylation upstream of GPNMB.
Methods
We retrieved genetic and DNA methylation data obtained from participants enrolled in the Taiwan Biobank (TWB) between 2008 and 2016. After excluding individuals with incomplete or missing information about potential PD risk factors, we included 1,357 participants in our final analyses. We used multiple linear regression to assess the association of GPNMB rs199347 and chronic alcohol consumption (and other potential risk factors) with GPNMB cg17274742 methylation.
Results
There was no difference between the distribution of GPNMB rs199347 genotypes between chronic alcohol consumers and the other study participants. A significant interaction was observed between the GPNMB rs199347 variant and alcohol consumption (p = 0.0102) concerning cg17274742 methylation. Compared to non-chronic alcohol consumers with the AA genotype, alcohol drinkers with the rs199347 GG genotype had significantly lower levels (hypomethylation) of cg17274742 (p = 0.0187).
Conclusion
Alcohol consumption among individuals with the rs199347 GG genotype was associated with lower levels of cg17274742 methylation, which could increase expression of the GPNMB gene, an important neuroinflammatory-related risk gene for PD.
