Ethanol Metabolism Research Articles

Characteristics and correlation of flavor substances and hangover indexes in Chinese baijiu during storage

It is generally believed that there is a great relationship between hangover and the age of Baijiu. However, what factors make Baijiu (stored for a long time) feel better after drinking has not been well explained. In this study, ethanol metabolism, oxidation stress, inflammation and release of inhibitory neurotransmitter were selected as the indicator of hangover. The results showed that the longer the age of Baijiu, the higher the antioxidant and anti-inflammatory levels, the less damage to the liver of mice. In addition, we also found that the longer the age of Baijiu, the faster the ethanol metabolism rate, the smaller the impact on the brain. A correlation analysis on Baijiu ingredients and hangover related indicators was conducted. These results showed that ethyl acetate, n-butanol, n-hexanol, butyl acetate, ethyl octanoate, isovaleric acid, 2-hydroxypropionic acid had a great correlation with all hangover related indicators.

Biological rhythms of the liver.

The biological rhythm is a fundamental aspect of an organism, regulating many physiological processes. This study focuses on the analysis of the molecular basis of circadian rhythms and its impact on the functioning of the liver. The regulation of biological rhythms is carried out by the clock system, which consists of the central clock and peripheral clocks. The central clock is located in the suprachiasmatic nucleus (SCN) of the hypothalamus and is regulated by signals received from the retinal pathway. The SCN regulates the circadian rhythm of the entire body through its indirect influence on the peripheral clocks. In turn, the peripheral clocks can maintain their own rhythm, independent of the SCN, by creating special feedback loops between transcriptional and translational factors. The main protein families involved in these processes are CLOCK, BMAL, PER and CRY. Disorders in the expression of these factors have a significant impact on the functioning of the liver. In such cases lipid metabolism, cholesterol metabolism, bile acid metabolism, alcohol metabolism, and xenobiotic detoxification can be significantly affected. Clock dysfunctions contribute to the pathogenesis of various disorders, including fatty liver disease, liver cirrhosis and different types of cancer. Therefore understanding circadian rhythm can have significant implications for the therapy of many liver diseases, as well as the development of new preventive and treatment strategies.

Genetic Polymorphism in Alcohol Metabolism and Drinking Behavior are Associated with Gastric Cancer Risk in Men.

Objective In recent years, there has been a growing focus on health risks associated with alcohol consumption. The present study investigated whether or not the genetic variant of aldehyde dehydrogenase 2 (ALDH2) influences the risk of gastric cancer among individuals identified as hazardous drinkers using the Alcohol Use Disorders Identification Test (AUDIT), which provides a comprehensive assessment of hazardous drinking behavior. Patients We enrolled men with hazardous drinking behavior (AUDIT score ≥ 8) who had undergone gastric cancer screening (either endoscopy or a barium X-ray examination of the upper gastrointestinal tract) between April 2013 and March 2020 within 1 year from entry and who had subsequently undergone at least one more gastric cancer screening up to March 2021. Functional single-nucleotide polymorphisms of ALDH2 (rs671) were measured using a direct TaqMan PCR method with unprocessed saliva. Results A total of 246 men were enrolled, comprising 193 individuals with active ALDH2 (ALDH2*1/*1) and 53 with less-active ALDH2 (ALDH2*1/*2). The cumulative incidence of gastric cancer in the less-active group was higher than in the active ALDH2 group (p=0.01, hazard ratio: 4.6, 95% confidence interval: 1.2-16.7). Alcohol consumption was lower in the less-active ALDH2 group than in the active ALDH2 group, although no marked difference was observed in the AUDIT score. Conclusion In individuals with hazardous drinking behavior, a heightened risk of gastric cancer was observed among those with less-active ALDH2 variants, even when their alcohol consumption was comparatively lower than in those with active ALDH2 variants.

Glucosamine attenuates alcohol-induced acute liver injury via inhibiting oxidative stress and inflammation

Alcohol liver disease (ALD) is a liver disease caused by long-term heavy drinking. Glucosamine (GLC) is an amino monosaccharide that plays a very important role in the synthesis of human and animal cartilage. GLC is commonly used in the treatment of mild to moderate osteoarthritis and has good anti-inflammatory and antioxidant properties. In this study, alcoholic injury models were constructed in mice and human normal hepatocyte L02 cells to explore the protective effect and mechanism of GLC on ALD. Mice were given GLC by gavage for 30 days. Liver injury models of both mice and L02 cells were produced by ethanol. Detecting the levels of liver injury biomarkers, lipid metabolism, oxidative stress biomarkers, and inflammatory factors through different reagent kits. Exploring oxidative and inflammatory pathways in mouse liver tissue through Western blot and RT-PCR. The results showed that GLC can significantly inhibit the abnormal increase of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), triglycerides (TG), total cholesterol (TC), very low density lipoprotein (VLDL), low-density lipoprotein cholesterol (LDL-C), and can significantly improve the level of high-density lipoprotein cholesterol (HDL-C). In addition, GLC intervention significantly improved alcohol induced hepatic oxidative stress by reducing the levels of malondialdehyde (MDA) and, increasing the levels of glutathione (GSH), catalase (CAT) and superoxide dismutase (SOD) in the liver. Further mechanisms suggest that GLC can inhibit the expression of ethanol metabolism enzyme cytochrome P4502E1 (CYP2E1), activate the antioxidant pathway Keap1/Nrf2/HO-1, down-regulate the phosphorylation of MAPK and NF-κB signaling pathways, and thus reduce the expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). Therefore, GLC may be a significant candidate functional food for attenuating alcohol induced acute liver injury.

Molecular insights on intracellular Wnt/β-catenin signaling in alcoholic liver disease.

Alcoholic liver disease (ALD) is one of the most common health problems worldwide, especially in developing countries caused by chronic consumption of alcohol on a daily basis. The ALD spectrum is initiated with the early stages of alcoholic fatty liver (steatosis), progressing to alcoholic steatohepatitis, followed by the later stages of fibrosis and in some cases, cirrhosis and hepatocellular carcinoma (HCC). The Wnt/β-catenin signaling required for healthy liver development, function, and regeneration is found to be aberrated in ALD, attributed to its progression. This review is to elucidate the association of Wnt/β-catenin signaling with various stages of ALD progression. Alcohol causes downregulation of Wnt/β-catenin signaling components and thereby suppressing the pathway. Reports have been published that aberrated Wnt/β-catenin signaling, especially the absence of β-catenin, results in decreased alcohol metabolism, causing steatosis followed by steatohepatitis via lipid accumulation, lipid peroxidation, liver injury, increased oxidative stress and apoptosis of hepatocytes, contributing to the advancement of ALD. Contrastingly, the progression of later stages of ALD like fibrosis and HCC depends on the increased activation of Wnt/β-catenin signaling and its components. Existing studies reveal the varied expression of Wnt/β-catenin signaling in ALD. However, the dual role of the Wnt/β-catenin pathway in earlier and later stages of ALD is not clear. Therefore, studies on the Wnt/β-catenin pathway and its components in various manifestations of ALD might provide insight in targeting the Wnt/β-catenin pathway in ALD treatment.

Anti-Teratogenic Potential of Exogenously Applied Over-The-Counter L-Glutathione Supplement on Ethanol-Induced Teratogenesis in Zebrafish (Danio rerio)

Glutathione is the body’s most abundant endogenous non-enzymatic antioxidant and is used as a substrate for free radical scavenging in the body, especially during ethanol metabolism. This study aims to shift the paradigm of using glutathione as a whitening agent into a potent antioxidant for therapy, particularly for ethanol-induced teratogenesis in the Philippines. Zebrafish embryos were treated with glutathione at various time points of ethanol exposure and concentration. Pre-treatments, co-treatments, and post-treatments with 100 μM glutathione solution were done to assess the most appropriate time point for glutathione intake upon exposure of the embryo to ethanol. Eye diameter and otic vesicle diameter were chosen as morphological parameters because dysmorphogenesis of these organs resembles mammalian fetal alcohol syndrome disorders. For eye diameter, alleviation of microphthalmia by glutathione was seen in pre-treatment (1% ethanol only) and post-treatment (1% & 1.5%) while co-treatment did not exhibit rescue for eye diameter reduction. For otic vesicle diameter, pre- and co-treatment with glutathione did not exhibit any changes in size but post-treatment showed abnormal enlargement suggesting possible teratogenic effect across all ethanol concentrations. The 2,2-diphenylpicryl-1-hydrazine (DPPH) assay was used as a confirmatory test for the free radical scavenging activity (FRSA) of treated tissues. Pre-treatment with GSH at 1% ethanol showed the highest FRSA while post-treatment showed FRSA insignificantly different to controls. This study suggests that glutathione can alleviate oxidative stress in embryo development which may lead to dysmorphogenesis and that supplementation before and after ethanol exposure may be a viable form of therapy for ethanol-induced teratogenesis.

Risk of newly developed atrial fibrillation by alcohol consumption differs according to genetic predisposition to alcohol metabolism: a large-scale cohort study with UK Biobank

BackgroundThe predictive relationship between mild-to-moderate alcohol consumption and the risk of incident atrial fibrillation (AF) remains controversial.ObjectiveWe investigated whether the relationship between alcohol consumption and the risk of incident AF could be associated with the genetic predisposition to alcohol metabolism.MethodsA total of 399,329 subjects with genetic data from the UK Biobank database, enrolled between 2006 and 2010, were identified and followed for incident AF until 2021. Genetic predisposition to alcohol metabolism was stratified according to the polygenic risk score (PRS) tertiles. Alcohol consumption was categorized as non-drinkers, mild-to-moderate drinkers (< 30 g/day), and heavy drinkers (≥ 30 g/day).ResultsDuring the follow-up (median 12.2 years), 19,237 cases of AF occurred. When stratified by PRS tertiles, there was a significant relationship between genetic predisposition to alcohol metabolism and actual alcohol consumption habits (P < 0.001). Mild-to-moderate drinkers showed a decreased risk of AF (HR 0.96, 95% CI 0.92–0.99), and heavy drinkers showed an increased risk of AF (HR 1.06, 95% CI 1.02–1.10) compared to non-drinkers. When stratified according to PRS tertiles for genetic predisposition to alcohol metabolism, mild-to-moderate drinkers had equivalent AF risks, and heavy drinkers showed increased AF risk in the low PRS tertile group. However, mild-to-moderate drinkers had decreased AF risks and heavy drinkers showed similar risks of AF in the middle/high PRS tertile groups.ConclusionsDifferential associations between alcohol consumption habits and incident AF across genetic predisposition to alcohol metabolism were observed; individuals with genetic predisposition to low alcohol metabolism were more susceptible to AF.

Exploring the genetic diversity of the Japanese population: Insights from a large-scale whole genome sequencing analysis.

The Japanese archipelago is a terminal location for human migration, and the contemporary Japanese people represent a unique population whose genomic diversity has been shaped by multiple migrations from Eurasia. We analyzed the genomic characteristics that define the genetic makeup of the modern Japanese population from a population genetics perspective from the genomic data of 9,287 samples obtained by high-coverage whole-genome sequencing (WGS) by the National Center Biobank Network. The dataset comprised populations from the Ryukyu Islands and other parts of the Japanese archipelago (Hondo). The Hondo population underwent two episodes of population decline during the Jomon period, corresponding to the Late Neolithic, and the Edo period, corresponding to the Early Modern era, while the Ryukyu population experienced a population decline during the shell midden period of the Late Neolithic in this region. Haplotype analysis suggested increased allele frequencies for genes related to alcohol and fatty acid metabolism, which were reported as loci that had experienced positive natural selection. Two genes related to alcohol metabolism were found to be 12,500 years out of phase with the time when they began to increase in the allele frequency; this finding indicates that the genomic diversity of Japanese people has been shaped by events closely related to agriculture and food production.

Kaempferol and nicotiflorin ameliorated alcohol-induced liver injury in mice by miR-138-5p/SIRT1/FXR and gut microbiota

AimsExcessive alcohol consumption can lead to alcoholic liver diseases (ALDs). Tetrastigma hemsleyanum Diels et Gilg is a rare Chinese medicinal herb. Tetrastigma hemsleyanum Diels et Gilg has been validated to be highly effective for treating hepatitis. Kaempferol and nicotiflorin are two highly representative flavonoids, which have exhibit therapeutic effects on liver disease. Therefore, the protective mechanism of kaempferol and nicotiflorin on alcohol-induced liver injury were investigated. Main methodsForty mice were used in this study. After treatment of Kaempferol and nicotiflorin, serum and liver were collected and used for determination of biochemical indicators, H&E staining, and molecular detection. The interaction of miRNAs from serum extracellular vehicles (EVs) with mRNAs and 16S rRNA sequencing of gut microbiota were also investigated. Key findingsThe results showed that kaempferol and nicotiflorins significantly ameliorated alcohol-induced liver damage and observably regulated gut microbiota. Specifically, the levels of malondialdehyde (MDA) and CYP2E1 in the liver significantly reduced, and the activity of superoxide dismutase (SOD) and glutathione (GSH) in the liver evidently increased. They also significantly relieved liver oxidative stress and lipid accumulation by suppressing miR-138-5p expression, inversely enhancing deacetylase silencing information regulator 2 related enzyme-1 (SIRT1) levels and then decreasing farnesoid X receptor (FXR) acetylation, which then modulated Nrf2 and SREBP-1c signaling pathways to regulate oxidative stress and lipid metabolism induced by alcohol. SignificanceKaempferol and nicotiflorin reduced alcohol-induced liver damage by enhancing alcohol metabolism and reducing oxidative stress and lipid metabolism. The intestinal microorganism disorder was also ameliorated after oral kaempferol and nicotiflorin.

A functional chicken-liver hydrolysate-based supplement ameliorates alcohol liver disease via regulation of antioxidation, anti-inflammation, and antiapoptosis.

Tons of broiler livers are produced yearly in Taiwan but always considered waste. Our team has successfully patented and characterized a chicken-liver hydrolysate (CLH) with several biofunctions. Chronic alcohol consumption causes hepatosteatosis or even hepatitis, cirrhosis, and cancers. This study was to investigate the hepatoprotection of CLH-based supplement (GBHP01™) against chronic alcohol consumption. Results showed that GBHP01™ could reduce (p < .05) enlarged liver size, lipid accumulation/steatosis scores, and higher serum AST, ALT, γ-GT, triglyceride, and cholesterol levels induced by an alcoholic liquid diet. GBHP01™ reduced liver inflammation and apoptosis in alcoholic liquid-diet-fed mice via decreasing TBARS, interleukin-6, interleukin-1β, and tumor necrosis factor-α levels, increasing reduced GSH/TEAC levels and activities of SOD, CAT and GPx, as well as downregulating CYP2E1, BAX/BCL2, Cleaved CASPASE-9/Total CASPASE-9 and Active CASPASE-3/Pro-CASPASE-3 (p < .05). Furthermore, GBHP01™ elevated hepatic alcohol metabolism (ADH and ALDH activities) (p < .05). In conclusion, this study prove the hepatoprotection of GBHP01™ against alcohol consumption.

Effects of Hovenia dulcis fruit and peduncle extract on alcohol metabolism

Ethnopharmacological relevanceThe dried fruit and peduncle of Hovenia dulcis Thunberg (Rhamnaceae) (HD) has been used as a folk medicine to treat liver disease, detoxify alcoholism, and prevent and cure hangovers. Aim of the studyWe investigated the pharmacology of HD on the kinetics of EtOH and on the enzymes related to alcohol metabolism to seek the scientific evidence of HD to prevent hangover, the effectiveness as a folk medicine. Materials and methodsEtOH was orally administered 30 min after oral administration of HD boiling water extract in rats. Then, the profiles of blood EtOH concentrations were measured. Mice were reared with food containing powdered HD for 7 days, and the activities of alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) in liver were measured. Hepa1c1c7 cells were cultured with the medium containing HD extract, and the activities of ADH and ALDH were measured. ResultsHD extract reduced the blood EtOH concentrations in rats and induced the activities of ADH and ALDH and mRNA and protein expressions of ADH1B, ALDH1A1, and ALDH2 in the liver of mice and Hepa1c1c7 cells. Dihydromyricetin, one of the ingredients of HD, significantly induced the activities of ADH and ALDH in Hepa1c1c7 cells, however, the fractions containing hydrophilic organic compounds with small molecular weight contributed the most of the activities of HD extract. ConclusionsWe clarified the experimental pharmacological evidences of HD as a folk medicine to detoxify alcoholism and prevent hangovers.

Cashew nut-supplemented diet on testicular injury in rats exposed to sub-acute alcohol

Binge drinking is a major global health issue, causing over 3.3 million mortalities yearly and might induce male infertility. Cashew nut contains many constituents with health benefits. This study investigated the effect of a cashew nut-supplemented diet (CND) against ethanol-invoked testicular injury in male Wistar rats. Thirty male rats were randomly assigned to five groups (n = 6). The groups are as follows: Group 1: (fed with standard diet only), Group 2: ethanol (received 30% v/v; 4 mL /kg body weight, orally) and regular diet, Group 3: (received ethanol and fed with 5% CND), Group 4: (received ethanol and provided with CND 10%), and Group 5: (10% CND) only. After fourteen days of ethanol administration and diet regimen, animals were fasted overnight and euthanized. Testis and blood were collected for biochemical and histological analyses. Testis was investigated for oxidative stress indices, glycogen level, antioxidant biomarkers, alcohol metabolism enzymes, and histopathology. Serum cholesterol, testosterone, and follicle-stimulating hormone (FSH) levels were also determined. Ethanol caused significant inhibition/reduction of antioxidant enzymes, cholesterol, testosterone, and FSH levels. Furthermore, there were increased levels of oxidative stress markers and histological impairment of the testis. However, the treatment with CND dose-dependently decreased the oxidative stress and aberrant histological features while augmenting the lowered antioxidant systems, normalizing the alcohol metabolizing enzymes and the hormones levels. This study shows that CND might protect against testicular injury by attenuating oxidative stress and boosting antioxidant and steroidogenesis in male rats.

Gut-derived ammonia contributes to alcohol-related fatty liver development via facilitating ethanol metabolism and provoking ATF4-dependent de novo lipogenesis activation

Background & aimsDysbiosis contributes to alcohol-associated liver disease (ALD); however, the precise mechanisms remain elusive. Given the critical role of the gut microbiota in ammonia production, we herein aim to investigate whether and how gut-derived ammonia contributes to ALD. MethodsBlood samples were collected from human subjects with/without alcohol drinking. Mice were exposed to the Lieber-DeCarli isocaloric control or ethanol-containing diets with and without rifaximin (a nonabsorbable antibiotic clinically used for lowering gut ammonia production) supplementation for five weeks. Both in vitro (NH4Cl exposure of AML12 hepatocytes) and in vivo (urease administration for 5 days in mice) hyperammonemia models were employed. RNA sequencing and fecal amplicon sequencing were performed. Ammonia and triglyceride concentrations were measured. The gene and protein expression of enzymes involved in multiple pathways were measured. ResultsChronic alcohol consumption causes hyperammonemia in both mice and human subjects. In healthy livers and hepatocytes, ammonia exposure upregulates the expression of urea cycle genes, elevates hepatic de novo lipogenesis (DNL), and increases fat accumulation. Intriguingly, ammonia promotes ethanol catabolism and acetyl-CoA formation, which, together with ammonia, synergistically facilitates intracellular fat accumulation in hepatocytes. Mechanistic investigations uncovered that ATF4 activation, as a result of ER stress induction and general control nonderepressible 2 activation, plays a central role in ammonia-provoked DNL elevation. Rifaximin ameliorates ALD pathologies in mice, concomitant with blunted hepatic ER stress induction, ATF4 activation, and DNL activation. ConclusionsAn overproduction of ammonia by gut microbiota, synergistically interacting with ethanol, is a significant contributor to ALD pathologies.

7. Adipose tissue: a critical organ involved in ethanol metabolism and alcohol induced liver injury

7. Adipose tissue: a critical organ involved in ethanol metabolism and alcohol induced liver injury

Enhanced sensitivity of a fluorometric biosensor for alcohol metabolites with an enzymatic cycling reaction

Assessing ethanol (EtOH) and acetaldehyde (AcH), metabolites of alcohol, enables more precise evaluation of alcohol metabolism. In this study, we developed a biosensor capable of concurrently measuring EtOH and AcH solutions with high sensitivity, utilizing a cycling reaction mediated by two enzymes: alcohol dehydrogenase (ADH) and alcohol oxidase (AOD). Within the cycling reaction, β-nicotinamide adenine dinucleotide (NADH, λex = 340 nm, λem = 490 nm) is oxidized when AcH is reduced to EtOH by ADH, while the EtOH produced in this reaction is oxidized by AOD, regenerating AcH. By detecting the consumption of oxygen or NADH in this reaction cycle, highly sensitive measurements of AcH and EtOH can be achieved. Initially, an AOD-ADH electrosensor was constructed to validate the feasibility of the cycling reaction by applying EtOH solution to the sensor. This electrosensor quantifies alcohol metabolites via the oxygen consumed in the cycling reaction, demonstrating a dynamic range for EtOH solution from 700 nM to 500 µM—a sensitivity two-fold greater than that achieved with the AOD membrane (1.4 µM–1 mM) alone. Subsequently, an ADH-AOD fluorosensor was developed, measuring alcohol metabolites via NADH consumption within the cycling reaction. The ADH-AOD fluorosensor demonstrated a dynamic range of 59 pM–100 µM for AcH solution, representing approximately a 1000-fold increase in sensitivity compared to the ADH membrane (70 nM–100 µM) alone. In future work, it is anticipated that utilizing this cycling reaction for the highly sensitive measurement of skin gases (EtOH and AcH) and facilitating non-invasive metabolic evaluations.

Protective Effects and Mechanism of Polysaccharides from Edible Medicinal Plants in Alcoholic Liver Injury: A Review.

Alcohol use accounts for a large variety of diseases, among which alcoholic liver injury (ALI) poses a serious threat to human health. In order to overcome the limitations of chemotherapeutic agents, some natural constituents, especially polysaccharides from edible medicinal plants (PEMPs), have been applied for the prevention and treatment of ALI. In this review, the protective effects of PEMPs on acute, subacute, subchronic, and chronic ALI are summarized. The pathogenesis of alcoholic liver injury is analyzed. The structure-activity relationship (SAR) and safety of PEMPs are discussed. In addition, the mechanism underlying the hepatoprotective activity of polysaccharides from edible medicinal plants is explored. PEMPs with hepatoprotective activities mainly belong to the families Orchidaceae, Solanaceae, and Liliaceae. The possible mechanisms of PEMPs include activating enzymes related to alcohol metabolism, attenuating damage from oxidative stress, regulating cytokines, inhibiting the apoptosis of hepatocytes, improving mitochondrial function, and regulating the gut microbiota. Strategies for further research into the practical application of PEMPs for ALI are proposed. Future studies on the mechanism of action of PEMPs will need to focus more on the utilization of multi-omics approaches, such as proteomics, epigenomics, and lipidomics.

Deciphering anaerobic ethanol metabolic pathways shaped by operational modes

Efficient anaerobic digestion requires the syntrophic cooperation among diverse microorganisms with various metabolic pathways. In this study, two operational modes, i.e., the sequencing batch reactor (SBR) and the continuous-flow reactor (CFR), were adopted in ethanol-fed systems with or without the supplement of powdered activated carbon (PAC) to examine their effects on ethanol metabolic pathways. Notably, the operational mode of SBR and the presence of CO2 facilitated ethanol metabolism towards propionate production. This was further evidenced by the dominance of Desulfobulbus, and the increased relative abundances of enzymes (EC: 1.2.7.1 and 1.2.7.11) involved in CO2 metabolism in SBRs. Moreover, SBRs exhibited superior biomass-based rates of ethanol degradation and methanogenesis, surpassing those in CFRs by 53.1% and 22.3%, respectively. Remarkably, CFRs with the extended solids retention time enriched high relative abundances of Geobacter of 71.7% and 70.4% under conditions with and without the addition of PAC, respectively. Although both long-term and short-term PAC additions led to the increased sludge conductivity and a reduced methanogenic lag phase, only the long-term PAC addition resulted in enhanced rates of ethanol degradation and propionate production/degradation. The strategies by adjusting operational mode and PAC addition could be adopted for modulating the anaerobic ethanol metabolic pathway and enriching Geobacter.

Alcohol induces ER stress and apoptosis by inducing oxidative stress and disruption of calcium homeostasis in glial cells

Alcohol has teratogenic effects that can cause developmental abnormalities and alter anatomical and functional characteristics of the developed brain and other organs. Glial cells play a crucial role in alcohol metabolism and protect neurons from toxic effects of alcohol. However, chronic alcohol exposure can lead to uncontrollable levels of reactive oxygen species, resulting in the death of glial cells and exposing neuronal cells to the toxic effects of alcohol. The exact molecular mechanism of alcohol-induced glial cell death has not been fully explored. This study reported that different concentrations of alcohol induce different expressions of ER stress markers in glial cells, focusing on the role of endoplasmic reticulum (ER) stress. Alcohol-induced concentration-dependent toxicity in both cells also induced oxidative stress, leading to mitochondrial damage. The expression of p53 and apoptotic proteins was significantly up-regulated after alcohol exposure, while Bcl2 (anti-apoptotic) was down-regulated. The signalling pathway for ER stress was activated and up-regulated marker proteins in a concentration-dependent manner. Cells pre-treated with BAPTA-AM and NAC showed significant resistance against alcohol assault compared to other cells. These in vitro findings will prove valuable for defining the mechanism by which alcohol modulates oxidative stress, mitochondrial and ER damage leading to glial cell death.

Fermented Protaetia brevitarsis Larvae Ameliorates Chronic Ethanol-Induced Hepatotoxicity in Mice via AMPK and TLR-4/TGF-β1 Pathways.

This study evaluated the hepatoprotective effect of fermented Protaetia brevitarsis larvae (FPB) in ethanol-induced liver injury mice. As a result of amino acids in FPB, 18 types of amino acids including essential amino acids were identified. In the results of in vitro tests, FPB increased alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activities. In addition, FPB treatment increased cell viability on ethanol- and H2O2-induced HepG2 cells. FPB ameliorated serum biomarkers related to hepatoxicity including glutamic oxaloacetic transaminase, glutamine pyruvic transaminase, total bilirubin, and lactate dehydrogenase and lipid metabolism including triglyceride, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. Also, FPB controlled ethanol metabolism enzymes by regulating the protein expression levels of ADH, ALDH, and cytochrome P450 2E1 in liver tissue. FPB protected hepatic oxidative stress by improving malondialdehyde content, reduced glutathione, and superoxide dismutase levels. In addition, FPB reversed mitochondrial dysfunction by regulating reactive oxygen species production, mitochondrial membrane potential, and ATP levels. FPB protected ethanol-induced apoptosis, fatty liver, and hepatic inflammation through p-AMP-activated protein kinase and TLR-4/NF-κB signaling pathways. Furthermore, FPB prevented hepatic fibrosis by decreasing TGF-β1/Smad pathway. In summary, these results suggest that FPB might be a potential prophylactic agent for the treatment of alcoholic liver disease via preventing liver injury such as fatty liver, hepatic inflammation due to chronic ethanol-induced oxidative stress.

Exploring the stress mechanism of tannic acid on Saccharomyces cerevisiae based on transcriptomics

Tannic acid is a polyphenolic substance widely in fruits, but the effect of tannic acid in fruit wine fermentation on Saccharomyces cerevisiae is still unknown. This study used tannic acid (1.6 g/L) to treat S. cerevisiae, the mechanism of the influence of tannic acid on the S. cerevisiae was further explored through transcriptomics technology. The results showed that the growth, ethanol yield and volatile substances of S. cerevisiae under tannic acid stress decreased by 71.76%, 46.49% and 85.58%, respectively. The activities of PDC and ADH of ethanol metabolism pathway decreased by 9.26% and 57.82%, respectively. Transcriptomic analysis showed that a total of 2890 differentially expressed genes were identified, of which 1499 genes were upregulated and 1391 genes were downregulated. Genes associated with the cell cycle, meiosis, and TCA cycle pathways were significantly induced, so S. cerevisiae responded to tannic acid stress through sexual reproduction and energy metabolism. The downregulation of genes related to cell wall integrity indicated that tannic acid destroyed the structure of the cell wall and inhibited its growth. In addition, downregulation of genes encoding glycolysis and pentose phosphate pathways were observed, resulting in significant inhibition of the ethanol metabolism pathway of S. cerevisiae. This study initially revealed the stress mechanism of tannic acid on S. cerevisiae and provided a basis for further studies to improve the tolerance in S. cerevisiae.