Ethanol-induced Liver Damage Research Articles

Haematococcus pluvialis polysaccharides improve microbiota-driven gut epithelial and vascular barrier and prevent alcoholic steatohepatitis development

Algal polysaccharides possess many biological activities and health benefits, such as antioxidant, anti-tumor, anti-coagulant, and immunomodulatory potential. Gut microbiota has emerged as one of the major contributor in mediating the health benefits of algal polysaccharides. In this study we showed that Haematococcus pluvialis polysaccharides (HPP) decreased serum transaminase levels and hepatic triglyceride content, alleviated inflammation and oxidative stress in the liver of chronic and binge ethanol diet-fed mice. Furthermore, HPP reduced endotoxemia, improved gut microbiota dysbiosis, inhibited epithelial barrier disruption and gut vascular barrier (GVB) damage in ethanol diet-fed mice. Co-housing vehicle-fed mice with HPP-fed mice alleviated ethanol-induced liver damage and endotoxemia. Moreover, fecal microbiota transplantation from HPP-fed mice into antibiotic-induced microbiota-depleted recipients also alleviated ethanol-induced liver injury and improved gut epithelial and vascular barrier. Our study demonstrated that HPP ameliorated ethanol-induced gut epithelial and vascular barrier dysfunction through alteration of gut microbiota, therefore preventing alcoholic liver damage.

Fruits of Emblica officinalis Linn. and its Phytochemicals in the Prevention of Ethanol-induced Hepatotoxicity: A Mini-Review

Abstract:: Excessive alcohol consumption over time is one of the primary causes of liver disease and death globally. Because there is no effective treatment, the situation has become more complicated, and the emphasis has shifted to the use of alternative and complementary medicine to treat liver problems. Herbs with dietary use have played an important part in the treatment of liver diseases since antiquity. Amla or Indian gooseberry, scientifically known as Phyllanthus emblica or Emblica officinalis, is a fruiting plant of the Phyllanthaceae family that is used in a variety of traditional and folk medical systems. The fruits have both dietary and medicinal value and are used to prevent chemical-induced hepatocarcinogenesis and reduce experimentally induced hyperlipidemia and metabolic syndrome in laboratory animals. They also have hepatoprotective effects against a variety of hepatotoxins such as heavy metals, iron overload, ochratoxins, hexachlorocyclohexane, carbon tetrachloride, therapeutic drugs such as paracetamol, and antitubercular. Amla fruits and phytochemicals such as quercetin, gallic acid, ellagic acid, and kaempferol are known to reduce ethanol-induced liver damage, and mechanistic studies have shown that the beneficial effects of these phytochemicals are mediated in part by free radical scavenging, antioxidant, and anti-inflammatory effects. This review examines the positive effects of amla fruit and its phytochemicals for the first time, as well as the mechanisms underlying the protective effects.

Bruceine A alleviates alcoholic liver disease by inhibiting AIM2 inflammasome activation via activating FXR

BackgroundAlcoholic liver disease (ALD), a public health challenge worldwide caused by long-term persistent drinking, is life-threatening with minimal approved therapies. Hepatic steatosis accompanied by inflammation is an initial and inevitable stage in the complex progression of simple alcoholic liver injury to more severe liver diseases such as hepatitis, liver fibrosis, cirrhosis and liver cancer. PurposeWe aimed to identify the therapeutic role of Bruceine A (BA) in ALD whilst attempting to explore whether its protective effects depend specifically on the farnesoid X receptor (FXR). MethodsAutodock was applied to detect the affinity between BA and FXR. Lieber-DeCarli liquid diet with 5 % ethanol (v/v) was adopted to establish the mouse ALD model. The lentivirus mediating FXR (LV-FXR) was injected into mice via the tail vein to establish FXR-overexpressed mice. FXR silencing or overexpression plasmids were transfected into AML-12 cells prior to ethanol stimulation. Quantitative real-time PCR, Western blotting and immunofluorescence assays were employed to determine the expression of related genes. We subjected liver sections to H&E and Oil Red O staining to evaluate the liver histological injury and the deposition of lipid droplets. ResultsBA significantly reduced body weight and liver-to-body weight ratios as well as biochemical indexes in mice. Ethanol-induced liver damage and lipid accumulation could be alleviated by BA treatment. BA bound to FXR by two hydrogen bonds. There was a positive correlation between BA administration and FXR expression. BA inhibited the expression of lipid synthesis genes and enhanced the expression of lipid metabolism genes by activating FXR, thus alleviating steatosis in ALD. Moreover, BA exerted an ameliorative effect against inflammation by inhibiting the activation of absent in melanoma 2 (AIM2) inflammasome by activating FXR. FXR overexpression possessed the ability to counter the accumulation of lipid and the activation of AIM2 inflammasome caused by ethanol. FXR deficiency exacerbated ethanol-induced liver steatosis and inflammation. The hepatoprotective effect of BA could be disrupted by FXR antagonist guggulsterone (GS) in vivo and FXR siRNA in vitro. ConclusionBA alleviated alcoholic liver disease by inhibiting AIM2 inflammasome activation through an FXR-dependent mechanism. This study may potentially represent a new therapeutic approach for ALD.

Bulbils of Aerial Yam Attenuate Ethanol-Induced Hepatotoxicity in HepG2 Cells through Inhibition of Oxidative Stress by Activation of the Nuclear Factor Erythroid-2-Related Factor 2 Signaling Pathway.

Bulbil of yam (BY) extract contains various active compounds possessing many pharmacological properties. However, little is known about the effect and underlying mechanism of BY extract on ethanol-induced liver damage. The present study explored the beneficial potential of BY extract on ethanol-induced hepatotoxicity. To evaluate its effectiveness, ethanol-induced HepG2 liver cells were pretreated with BY extract. BY extract effectively rescued cells from ethanol treatment through inhibition of apoptotic cell death as well as inhibiting expression of mitogen-activated protein kinase (MAPK) proteins as stress inducers. BY extract increased the expression of typical antioxidants. Furthermore, BY extract significantly inhibited mitochondrial dysfunction and endoplasmic reticulum (ER) stress, which are major ROS-inducing factors. Finally, as an underlying mechanism of the protective effects of BY extract on ethanol-induced liver damage, it activated Nrf2 protein through translocation from the cytosol to the nucleus, which in turn activated its target oxidative stress suppressor genes. Collectively, our findings demonstrate that BY extract has potential antioxidative effects in ethanol-induced liver cells and contributes to the establishment of a treatment strategy for alcohol-derived liver injuries.

The influence of phenformin on the extracellular matrix of the liver of rats under long-term administration of ethanol [

Experimental and clinical studies have revealed the influence of AMP-activated protein kinase (AMPK) signaling on the development of non-alcoholic liver fibrosis. Currently, the results of experimental studies demonstrate that inhibition of AMPK promotes fibrogenesis, while its activation prevents the development of liver fibrosis. The purpose of this work is to establish the effect of activation of AMP-activated protein kinase by the administration of phenformin on the content of glycosaminoglycans, oxyproline and sialic acids in the liver of rats under the conditions of long-term administration of ethanol. The study was conducted on 24 male Wistar rats. The animals were randomly divided into 4 groups of 6 animals each, on which we modeled ethanol-induced liver damage and administered phenformin hydrochloride at a dose of 10 mg/kg. The experiment lasted 63 days. In the liver of rats, the content of total glycosaminoglycans, the concentration of heparin-heparan, keratan-dermatan and chondroitin fractions of glycosaminoglycans, the content of free oxyproline and sialic acids were studied. Long-term alcoholization leads to a violation of the extracellular matrix of the liver of rats, which is evidenced by a decrease in the concentration of proteoglycans and a redistribution of their fractions in the direction of a decrease in anti-inflammatory and regenerative fractions. Chronic intake of alcohol increases the processes of desialylation of glycoconjugates and the intensity of collagenolysis. Activation of AMP-activated protein kinase by administration of phenformin under the conditions of simulating ethanol-induced liver damage leads to an increase in the concentration of glycosaminoglycans due to the growth of heparin-heparan and chondroitin fractions and reduces the intensity of desialylation of glycoconjugates and collagenolysis in the liver of rats.

Oral Administration of Alcohol-Tolerant Lactic Acid Bacteria Alleviates Blood Alcohol Concentration and Ethanol-Induced Liver Damage in Rodents.

Excessive alcohol consumption can have serious negative consequences on health, including addiction, liver damage, and other long-term effects. The causes of hangovers include dehydration, alcohol and alcohol metabolite toxicity, and nutrient deficiency due to absorption disorders. Additionally, alcohol consumption can slow reaction times, making it more difficult to rapidly respond to situations that require quick thinking. Exposure to a large amount of ethanol can also negatively affect a person's righting reflex and balance. In this study, we evaluated the potential of lactic acid bacteria (LAB) to alleviate alcohol-induced effects and behavioral responses. Two LAB strains isolated from kimchi, Levilactobacillus brevis WiKim0168 and Leuconostoc mesenteroides WiKim0172, were selected for their ethanol tolerance and potential to alleviate hangover symptoms. Enzyme activity assays for alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) were then conducted to evaluate the role of these bacteria in alcohol metabolism. Through in vitro and in vivo studies, these strains were assessed for their ability to reduce blood alcohol concentrations and protect against alcohol-induced liver damage. The results indicated that these LAB strains possess significant ethanol tolerance and elevate ADH and ALDH activities. LAB administration remarkably reduced blood alcohol levels in rats after excessive alcohol consumption. Moreover, the LAB strains showed hepatoprotective effects and enhanced behavioral outcomes, highlighting their potential as probiotics for counteracting the adverse effects of alcohol consumption. These findings support the development of functional foods incorporating LAB strains that can mediate behavioral improvements following alcohol intake.

Histopathological and Biochemical Investigation of the Effect of Shepherd's Purse (Capsella bursa-pastoris L.) on Ethanol-Induced Liver Damage

Histopathological and Biochemical Investigation of the Effect of Shepherd's Purse (Capsella bursa-pastoris L.) on Ethanol-Induced Liver Damage

Hydrogen gas alleviates acute ethanol-induced hepatotoxicity in mice via modulating TLR4/9 innate immune signaling and pyroptosis

Alcoholic liver disease (ALD), which is induced by chronic heavy alcohol consumption, accompanies complicated pathological mechanisms, including oxidative stress, inflammation, cell death, epigenetic changes and acetaldehyde-mediated toxicity. Hydrogen (H2) is the lightest gas with multiple biological effects such as high selective anti-oxidation, anti-inflammation and anti-apoptosis. However, the dose effects and innate immune mechanisms of intraperitoneal injection of H2 on ALD are limited. Here, we used acute ethanol-induced hepatotoxicity mice models to estimate the actions of intraperitoneal injection of H2 on ALD. The effects of H2 on acute ethanol-induced liver damage were examined by hepatic oil red O staining, quantitative PCR (qPCR) for lipid metabolic genes, hepatic triglyceride (TG) and serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Hepatic mitochondrial superoxide (MitoSOX), 3-nitrotyrosine (3-NT), malondialdehyde (MDA), and glutathione (GSH) levels were examined to evaluate oxidative stress. Immunoblot, and immunofluorescence staining were used to further confirm the innate immune molecular targets of H2. Our results showed that intraperitoneal injection of H2 improved acute ethanol-induced liver injury in mice in a dose dependent manner, as indicated by decreasing serum ALT and AST levels, hepatic TG levels, and increasing lipid export genes (Mttp and Apob) mRNA levels and reducing fatty acid uptake gene (CD36) mRNA levels. Mechanistically, H2 inhibited hepatic oxidative stress as indicated by reducing reactive oxygen species (ROS), 3-NT, and MDA levels in the liver, while increasing hepatic GSH levels; inhibited the overactived TLR4/9-NF-κB-TNF-α/IL-1β/IL-18 innate immune signaling; suppressed the canonical Caspase-1-GSDMD pyroptosis signaling, and the non-canonical pyroptosis signaling, such as Caspase-11-GSDMD, Caspase-8-GSDMD and Caspase-3-GSDME signaling. Therefore, our study highlights that intraperitoneal injection of H2 may represent a novel therapeutic and safe strategy for ALD via modulating oxidative stress, innate immunity and pyroptosis.

Combination of Cysteine and Glutathione Prevents Ethanol-Induced Hangover and Liver Damage by Modulation of Nrf2 Signaling in HepG2 Cells and Mice.

Excessive alcohol consumption increases oxidative stress, leading to alcoholic liver disease. In this study, the protective effects of a mixture of cysteine and glutathione against ethanol-induced hangover and liver damage were evaluated in mice and HepG2 cells. Ethanol (2 mL/kg) was orally administered to the mice 30 min before receiving the test compounds (200 mg/kg), and the behavioral and oxidative stress-related biochemical parameters altered by ethanol were analyzed. Acute ethanol administration increased anxiety behavior and decreased balance coordination in mice (p < 0.001); however, a mixture of cysteine and glutathione (MIX) in a 3:1 ratio improved alcohol-induced behavior more effectively than the individual compounds (p < 0.001). The MIX group showed higher ethanol-metabolizing enzyme activity than the control group (p < 0.001) and significantly suppressed the elevation of serum alcohol (p < 0.01) and acetaldehyde (p < 0.001) levels after 1 h of ethanol administration. In HepG2 cells, 2.5 mM MIX accelerated ethanol metabolism and reduced cytochrome P450 2E1 mRNA expression (p < 0.001). MIX also increased the expression of antioxidant enzymes through the upregulation of nuclear erythroid 2-related factor 2 (Nrf2) signaling and consequently suppressed the overproduction of reactive oxygen species and malondialdehyde (p < 0.001). Collectively, MIX alleviates the hangover symptoms and attenuates the alcohol-induced oxidative stress by regulating the Nrf2 pathway.

Hepatoprotective and hypoglycemic effect of lactic acid fermented Indian Gooseberry-Amla beverage on chronic alcohol-induced liver damage and diabetes in rats

BackgroundPlant-based fermented foods rich in lactic acid bacterial metabolites, antioxidants, and phytochemicals, can promote recovery from ethanol-induced liver damage by restoring liver antioxidant levels and suppressing liver inflammation, and improving certain metabolic disorders such as diabetes mellitus. MethodsIn the present study, the protective effects of nutraceutical-enriched lactic acid-fermented Amla beverage on chronic alcohol-induced biochemical modulations and diabetes in Wistar rats were investigated. ResultsThe hepatoprotective studies showed that the fermented beverage was able to reverse the damage caused to the liver with ethanol administration in terms of liver index, liver enzymes (AST, ALT), serum enzymes (g-GT), and serum TG, TCH, hepatic TG, LPO levels, antioxidants (GSH, TSOD, CAT, GSH-Px). Along similar lines, in the hypoglycemic studies, the fermented beverage evidently improved body weight, and fasting blood glucose levels, reducing fasting HbAlc levels, improving C-peptide and GLP-1 levels, and alleviating renal dysfunction and lipid metabolism compared with diabetic rats. All these outcomes were supported by histological observations within the liver and pancreas. ConclusionThe present study suggests that the consumption of fermented Amla beverage may have a protective effect against chronic alcohol-induced toxicity and diabetes. The effects of fermented Amla beverage may be attributed to antioxidant activity, flavonoids, bioactive compounds produced by LAB and their metabolites, which help to counteract free radicals induced by ethanol and in reducing glucagon levels, enhancing glucose utilization, leading to a decrease in blood glucose. The results show that fermented Amla beverage has positive effects in reducing the detrimental effect of alcohol and diabetes.

The influence of hormonal status on the hepatotropic effect and metronidazole in chronic liver damage and the administration of placenta cryoextract

Background. Liver diseases occupy an important place in the structure of gastrointestinal pathology and remain an important medical and social problem throughout the world. Almost half of patients with manifest disorders of the hepatobiliary system have a polymorbid status or a high risk of developing concomitant pathology. One of the variants of the combined pathology in the clinic of gastroenterology is peptic ulcer on the background of liver disorders. As a potential anti-ulcer biotechnological agent with a hepatoprotective effect, cryocell — placenta cryoextract, a domestic drug, attracted attention. The purpose was to determine the gender aspects of the hepatotropic effect of placenta cryoextract in tetrachloromethane hepatitis with background ethanol-induced liver cirrhosis and liver damage by antiulcer agents. Materials and methods. Hepatotropic effects were studied at different levels of sex hormones in 112 male and female rats weighing 200–220 g, divided into 4 groups of 28 animals each. Tetrachloromethane hepatitis with background ethanol-induced liver cirrhosis was simulated by administration of an oily solution of tetrachloromethane in combination with a 5.0% ethanol solution for 45 days. Modulation of the content of sex hormones was achieved by surgical ovariectomy or orchiectomy. The activity of γ-glutamyl-transpeptidase was determined by the spectrophotometric method according to G. Szasz.

High-fat diet promotes multiple binges-induced liver injury via promoting hepatic macrophage proinflammatory polarization.

High-fat diet (HFD) and ethanol could synergistically induce liver damage, but the underlying mechanisms remain to be elucidated. M1-polarized macrophages have been demonstrated to be key players in ethanol-induced liver damage. The current study was designed to investigate whether hepatic steatosis could promote ethanol-induced liver injury by promoting liver macrophage M1 polarization. In the in vivo study, 12weeks of HFD feeding induced a moderate increase in the F4/80 expression and protein levels of p-IKKα/β, p-IκBα, and p-p65, which was suppressed by single binge. In contrast, 8weeks of HFD and multiple binges (two binges per week during the last 4weeks) synergistically increased the F4/80 expression, mRNA levels of M1 polarization biomarkers including Ccl2, Tnfa, and Il1b, and protein levels of p65, p-p65, COX2, and Caspase 1. In the in vitro study, a nontoxic free fatty acids (FFAs) mixture (oleic acid/palmitic acid=2: 1) induced a moderate increase of protein levels of p-p65 and NLRP3 in murine AML12 hepatocytes, which was inhibited by ethanol co-exposure. Ethanol alone induced proinflammatory polarization of murine J774A.1 macrophages evidenced by the enhanced secretion of TNF-α, increased mRNA levels of Ccl2, Tnfa, and Il1b, and upregulated protein levels of p65, p-p65, NLRP3, and Caspase 1, which was augmented by FFAs exposure. Collectively, these results suggest that HFD and multiple binges could synergistically induce liver damage by promoting the proinflammatory activation of macrophages in mice livers.

Tgr5-/- mice are protected from ethanol-induced metabolic alterations through enhanced leptin and Fgf21 signaling.

Alcohol-associated liver disease (ALD) is caused by chronic use of alcohol and ranges from hepatic steatosis to fibrosis and cirrhosis. Bile acids are physiological detergents that also regulate hepatic glucose and lipid homeostasis by binding to several receptors. One such receptor, Takeda G protein-coupled receptor 5 (TGR5), may represent a therapeutic target for ALD. Here, we used a chronic 10-day + binge ethanol-feeding model in mice to study the role of TGR5 in alcohol-induced liver injury. Female C57BL/6J wild-type mice and Tgr5-/- mice were pair-fed Lieber-DeCarli liquid diet with ethanol (5% v/v) or isocaloric control diet for 10 days followed by a gavage of 5% ethanol or isocaloric maltose control, respectively, to represent a binge-drinking episode. Tissues were harvested 9 hours following the binge, and metabolic phenotypes were characterized through examination of liver, adipose, and brain mechanistic pathways. Tgr5-/- mice were protected from alcohol-induced accumulation of hepatic triglycerides. Interestingly, liver and serum levels of Fgf21 were significantly increased during ethanol feeding in Tgr5-/- mice, as was phosphorylation of Stat3. Parallel to Fgf21 levels, increased leptin gene expression in white adipose tissue and increased leptin receptor in liver were detected in Tgr5-/- mice fed ethanol diet. Adipocyte lipase gene expression was significantly increased in Tgr5-/- mice regardless of diet, whereas adipose browning markers were also increased in ethanol-fed Tgr5-/- mice, indicating potential for enhanced white adipose metabolism. Lastly, hypothalamic mRNA targets of leptin, involved in the regulation of food intake, were significantly increased in Tgr5-/- mice fed ethanol diet. Tgr5-/- mice are protected from ethanol-induced liver damage and lipid accumulation. Alterations in lipid uptake and Fgf21 signaling, and enhanced metabolic activity of white adipose tissue, may mediate these effects.

Autophagy and exosomes coordinately mediate quercetin's protective effects on alcoholic liver disease

Alcoholic liver disease (ALD), a spectrum of liver abnormalities induced by chronic alcohol abuse, continues to be the major cause of life-threatening liver disease in developed countries. Autophagy and exosomes were individually confirmed to be involved in the pathogenesis of ALD. Here, we sought to identify the role of autophagy and exosomes in the liver protective effects of quercetin. We observed decreased hepatic LC3II/LC3I and increased p62 level in ethanol-fed mice, and these changes were alleviated by quercetin. Meanwhile, nanoparticle tracking analysis (NTA) showed elevated serum exosomes numbers in ethanol-fed mice, which was combated by quercetin. Ethanol induced elevated LDH, ALT, and AST in HepG2 supernatant, which was alleviated by cytochalasin D (exosomes uptake inhibitor). Moreover, quercetin reduced ethanol-induced LDH and ALT elevation in vitro, and the effects of quercetin were reversed by Rab27a overexpression (induce exosomes release) or wortmannin treatment (autophagy inhibitor). Transcriptomic analysis supported that quercetin reversed the change of lysosome related genes disturbed by ethanol. Meanwhile, western blot analysis exhibited decreased hepatic expression of LAMP2 and ATPA6V1B2, and active Cathepsin B/Cathepsin B by quercetin treatment, indicating quercetin alleviated lysosome dysfunction in ethanol-fed mice. Baf A treatment or transfection of siTFEB offset quercetin's effects in ethanol-induced LDH and ALT elevation, exosomes release, and autophagy inhibition (LC3II/I and p62 accumulation). Taken together, quercetin coordinately activates autophagy and combats exosomes release by restoring lysosome function, and further mitigates ethanol-induced liver damage.

Hangover-Relieving Effect of Ginseng Berry Kombucha Fermented by Saccharomyces cerevisiae and Gluconobacter oxydans in Ethanol-Treated Cells and Mice Model.

This study aimed to evaluate the hangover relieving effect of ginseng berry kombucha (GBK) fermented with Saccharomyces cerevisiae and Gluconobacter oxydans in in vitro and in vivo models. The antioxidant activity and oxidative stress inhibitory effect of GBK were evaluated in ethanol-treated human liver HepG2 cells. In addition, biochemical and behavioral analyses of ethanol treated male ICR mice were performed to confirm the anti-hangover effect of GBK. The radical scavenging activity of GBK was increased by fermentation, and the total ginsenoside content of GBK was 70.24 μg/mL. In HepG2 cells, in which oxidative stress was induced using ethanol, GBK significantly increased the expression of antioxidant enzymes by upregulating the Nrf2/Keap1 pathway. Moreover, GBK (15 and 30 mg/kg) significantly reduced blood ethanol and acetaldehyde concentrations in ethanol-treated mice. GBK significantly increased the levels of alcohol-metabolizing enzymes, including alcohol dehydrogenase and acetaldehyde dehydrogenase. The balance beam test and elevated plus maze test revealed that high-dose GBK significantly ameliorated ethanol-induced behavioral changes. Collectively, GBK exerted a protective effect against ethanol-induced liver damage by regulating the Nrf2/Keap1 pathway.

Gender determinism of the effect of placenta cryoextract on the hepatotropic effects of esomeprazole, clarithromycin and metronidazole in chronic liver damage

Current regimens for the eradication of Helicobacter pylori infection include bismuth drugs, proton pump inhibitors, and a combination of 2–3 antibacterial drugs. Uncontrolled use of antibacterial agents as part of eradication schemes increases the risk of developing their unwanted drug reactions, in particular, hepatotoxicity. As a means with potentially hepatoprotective activity, our attention was drawn to placental cryoextract.&#x0D; The purpose of the study. To characterize the gender aspects of the hepatotropic action of placenta cryoextract in tetrachloromethane hepatitis with background ethanol-induced cirrhosis and liver damage by antiulcer agents.&#x0D; Materials and methods. Research was conducted on 112 male and female rats. Tetrachloromethane hepatitis with background ethanol-induced liver cirrhosis was reproduced by injecting an oil solution of CCl4 in combination with a 5.0% ethanol solution for 45 days. Modulation of the content of sex hormones was achieved by surgical ovariectomy or testectomy.&#x0D; Results and discussion. Administration of esomeprazole, clarithromycin, and metronidazole in chronic liver damage in animals without changes in hormonal status led to a statistically significant (p=0.01) 27.6% increase in the level of bilirubin in homogenates of liver tissues in female rats (78.7±4.5 mmol/l) than in males. The greatest decrease in the content of bilirubin (41.7%, p&lt;0.001) with the use of cryoextract of the placenta was noted in castrated female rats with simulated tetrachlormethone hepatitis with background ethanol-induced cirrhosis of the liver, which were injected with antiulcer agents.&#x0D; Conclusions. Administration of cryoextract of the placenta has a pronounced hepatoprotective effect in animals of both sexes. In male rats with no change in hormonal status with simulated liver injury and the administration of antiulcer drugs, placenta cryoextract therapy was more effective than in female rats, as indicated by a more than 1.6-fold decrease in the content of bilirubin in the liver homogenates of male rats (43.1%, p&lt;0.001) than in females (27.4%, p&lt;0.01).

Bacillus subtilis pretreatment alleviates ethanol-induced acute liver injury by regulating the Gut-liver axis in mice

This study was designed to investigate the hepatoprotective effects of Bacillus subtilis, a commensal bacterial species in the human gut, on ethanol-induced acute liver damage and the underlying mechanisms in mice. Male ICR mice challenged with three doses of ethanol (5.5 g/kg BW) exhibited a significant increase in serum aminotransferase activities and TNF-α level, liver fat accumulation, and activation of NF-κB signaling and NLRP3 inflammasome, which was suppressed by pretreatment with Bacillus subtilis. Besides, Bacillus subtilis inhibited acute ethanol-induced intestinal villi shortening and epithelial loss, the decline of protein levels of intestinal tight junction protein ZO-1 and occludin, and elevation of serum LPS level. Furthermore, the upregulation of mucin-2 (MUC2) and the downregulation of anti-microbial Reg3B and Reg3G levels induced by ethanol were repressed by Bacillus subtilis. Lastly, Bacillus subtilis pretreatment significantly increased the abundance of the intestinal Bacillus, but had no effects on the binge drinking-induced increase of Prevotellaceae abundance. These results demonstrate that Bacillus subtilis supplementation could ameliorate binge drinking-induced liver injury, and thus may serve as a functional dietary supplement for binge drinkers.

Lutein Prevents Liver Injury and Intestinal Barrier Dysfunction in Rats Subjected to Chronic Alcohol Intake

Chronic alcohol intake can affect both liver and intestinal barrier function. The goal of this investigation was to evaluate the function and mechanism of lutein administration on the chronic ethanol-induced liver and intestinal barrier damage in rats. During the 14-week experimental cycle, seventy rats were randomly divided into seven groups, with 10 rats in each group: a normal control group (Co), a control group of lutein interventions (24 mg/kg/day), an ethanol model group (Et, 8-12 mL/kg/day of 56% (v/v) ethanol), three intervention groups with lutein (12, 24 and 48 mg/kg/day) and a positive control group (DG). The results showed that liver index, ALT, AST and TG levels were increased, and SOD and GSH-Px levels were reduced in the Et group. Furthermore, alcohol intake over a long time increased the level of pro-inflammatory cytokines TNF-α and IL-1β, disrupted the intestinal barrier, and stimulated the release of LPS, causing further liver injury. In contrast, lutein interventions prevented alcohol-induced alterations in liver tissue, oxidative stress and inflammation. In addition, the protein expression of Claudin-1 and Occludin in ileal tissues was upregulated by lutein intervention. In conclusion, lutein can improve chronic alcoholic liver injury and intestinal barrier dysfunction in rats.

Mechanistic role of epigallocatechin-3-gallate in regulation of the antioxidant markers in ethanol induced liver damage in mice

ABSTRACT Background: Failure of endogenous antioxidant system to eliminate high levels of ROS results to oxidative stress, consequently leading to liver damage. Excessive alcohol consumption leads to liver damage due to ROS generation, thus regarded as the leading causes of death worldwide, suggesting great need for use of exogenous antioxidants like epigallocatechin-3-gallate (EGCG), to avert liver damage. However, underlying EGCG mechanisms remains elusive.Aim of the work: This study focused on mechanistic role of EGCG in regulation of antioxidant marker activities during ethanol induced liver damage.Materials and Methods: 20 male Swiss Albino mice were divided into four groups and treated with different dosage. ALT, AST and total proteins were determined as indicators of liver damage. MDA and protein carbonyls were measured as oxidative stress markers. Activities of SOD and CAT were determined. SOD-2 and CAT differential gene expression were also determined. Liver histology analysis by H&E staining. All the experiments were run in duplicates. ANOVA was used to analyzes data using Tukey’s multiple comparison tests and results considered statistically significant if p ≤ 0.05 at 95% confidence level. Results: Findings revealed that chronic consumption of ethanol leads to liver damage through increased levels of serum ALT and AST, MDA, protein carbonyls and remarkable diffuse lipid droplets and decreased enzyme activity of SOD and CAT. EGCG increased activity of SOD and CAT and SOD-2 expression and did not affect CAT expression. Conclusion: In summary, ethanol induces liver damage, and administration of EGCG increases antioxidant system expression, suggesting its role in regulating their activities, defensive of oxidative stress through various pathways.

Thymol ameliorates ethanol-induced hepatotoxicity via regulating metabolism and autophagy

Alcoholic liver disease represents a serious threat to human health. In terms of safety and acceptability, thymol is widely used in or on foodstuffs to generate odour and taste. The present study aimed to investigate the therapeutic effect and mechanism of thymol against ethanol-induced injury in liver cells. Here we found that thymol is an effective agent for reducing ethanol-induced reactive oxygen species production in mouse liver cells. Thymol improves ethanol-induced lipid accumulation, and this corresponded to altered DGAT2 mRNA expression levels. Metabolomics data analysis showed that thymol alleviated ethanol-induced changes in the levels of thirty-four metabolites including nicotinic acid and l-arginine. By utilizing pathway enrichment analysis, altered metabolites in cells treated with ethanol and ethanol plus thymol were enriched in fourteen pathways including metabolic pathways and arginine and proline metabolism. We further confirmed the alleviation of overdose nitric oxide production in cells treated with ethanol plus thymol compared with that in ethanol-treated cells. It was interesting that up-regulated LC3-II/LC3-I ratio together with higher SQSTM1 protein abundance in ethanol-treated cells were attenuated by treatment with ethanol plus thymol. Thymol ameliorated ethanol-induced reduction of HSPA8 protein abundance. In addition, chloroquine-treated cells exhibited lower HSPA8 protein abundance compared with cells simulated with ethanol plus thymol. These data reveal that improving effect of thymol on ethanol-induced metabolic alteration is related to autophagic flux restoration. Our findings indicate that thymol is an attractive option for treating ethanol-induced liver damage.