Ethanol-induced Hepatotoxicity Research Articles

Ameliorative effect of flaxseed (Linum usitatissimum) and its protein on ethanol-induced hepatotoxicity in Wistar rats.

Hepatoprotective effect of flaxseed and its protein on ethanol-induced hepatotoxicity in adult Wistar rats was investigated. The rats were divided into eight groups of which two served as control (group I: Control for AIN-93M diet groups and group II: Control for cereal-pulse diet groups) and six groups received ethanol orally every day. After 10days along with ethanol, the rats received AIN-93M diet (group III); AIN-93M diet and commercial hepatoprotective formulation (CHF) (group IV); casein replaced by flaxseed protein in AIN-93M diet (group V); cereal-pulse diet (group VI); cereal-pulse diet and CHF (group VII); cereal-pulse diet containing flaxseed (group VIII) for four weeks. The flaxseed and its protein significantly prevented the elevation of plasma markers of hepatic damage, lowered lipid peroxidation, mitigated changes in antioxidant enzymes, and suppressed histopathological signs of hepatic damage. The hepatoprotective effect of flaxseed and its protein was comparable to CHF. These findings implicate the ameliorative effect of flaxseed and its protein on ethanol-induced hepatotoxicity. PRACTICAL APPLICATIONS: Owing to globalization and an increase in earning capacity, alcohol consumption is becoming a part of social life and gradually transforming to addiction. Binge drinking is highly prevalent among low socioeconomic status population, which poses severe risks to health. Alcohol abuse is a public health problem causing three million deaths annually worldwide. Alcohol consumption is known to be a major cause of liver damage worldwide and has contributed to 44% of deaths from liver disease. As abstaining from alcohol is a challenging task, there is an escalating need to formulate potential hepatoprotective agents to prevent alcohol-induced hepatic damage. This study investigates the efficacy of flaxseed and its protein in conferring protection to the liver against ethanol-induced hepatotoxicity. This study also explores the benefits of incorporating flaxseed in the staple cereal-pulse diet. Findings of this study suggest that incorporation of flaxseed or its protein in food formulations can prevent hepatotoxicity and improve the overall quality of life among alcoholics.

Relative protective activities of quercetin, quercetin-3-glucoside, and rutin in alcohol-induced liver injury.

Alcoholic liver diseases has been known to be one of the major health risks worldwide. The purpose of this study was aimed to demonstrate the relative protective effect of quercetin, quercetin-3-glucoside, and rutin on alcohol-induced damage in hepatocytes. The hepatotoxicity, antioxidant enzymatic defense mechanisms, and pro-inflammatory mediators were examined for evaluating the hepatoprotective effects of quercetins in hepG2 cells. The results revealed that quercetin and its glucoside derivatives significantly prevented ethanol-induced hepatotoxicity by decreasing hepatic aminotransferase activities and inflammatory response in HepG2 cells. Moreover, the quercetins significantly induced detoxifying enzymes via the nuclear accumulation of the NF-E2-related factor 2 (Nrf2) and induction of antioxidant response element (ARE) gene. These hepatoprotective activities were observed to be more effective with quercetin aglycone than quercetin glucosides. From the above findings, the present study imply that quercetin aglycone may have a vital function in the therapeutic and preventive strategies of alcoholic liver diseases. PRACTICAL APPLICATIONS: Quercetin is commonly present in fruits and vegetables as aglycone and glucoside-derived forms. In the present study, quercetin and its glycosides was shown to alleviate oxidative stress, glutathione depletion, and pro-inflammatory cytokines in alcohol-induced HepG2 cells via the Nrf2/ARE antioxidant pathway. Moreover, quercetin aglycone had better protective effects against alcohol-induced liver damage in vitro, compared to its glycosylated form. The present study proposed that quercetin aglycone may be a more efficient hepatoprotective agent than its glucoside derivatives such as rutin in the amelioration of alcohol-induced liver diseases.

EFFECT OF CULTURAL CONDITION ON EVALUATION OF HEPATOPROTECTIVE ACTIVITY OF METHANOLIC BARK EXTRACT OF ANOGEISSUS LATIFOLIA ON ETHANOL-INDUCED HEPATOTOXICITY

Objective: Geographical location has a great importance on phytoconstituents content in plants. The present study was aimed to understand the impact of soil nature of geographical zone on evaluation of hepatoprotective activity Anogeissus latifolia (AL), (family: Combretaceae) methanolic bark extract on ethanol-induced hepatotoxicity in Wistar rats.Methods: Soil sample was collected and analyzed for various physicochemical properties. Atomic absorption spectrophotometer was used for determination of heavy metals present in soil sample. Thereafter, liver damage was produced by ethanol (3.76 g/kg p.o). The plant extract was administered orally for 25 days. At the end of the study, the biochemical parameters were investigated. Silymarin was used as a standard. Furthermore, histopathology was carried out and characterized by severe vacuolar, cytoplasmic degeneration, and hepatic necrosis. Finally, the impact of soil parameters is correlated with the evaluated study.Results: Analyzed soil sample showed pH is acidic (pH=5.48) and presence of higher amount of iron (Fe), copper (Cu), and zinc (Zn) (77.37 mg/kg, 10.87 mg/kg, and 19.26 mg/kg, respectively) whereas other metals such as nickel, chromium, cadmium, and lead are present in less content. Thereafter, treatment of animals with methanolic extract of AL bark significantly (p<0.05) decrease the levels of serum glutamic oxaloacetic transaminase in serum which is an indicative of hepatoprotective activity. Also brought down the level of serum glutamic pyruvic transaminase significantly (p<0.05 in 200 mg/kg b.w. and 400 mg/kg b.w. doses, respectively). Various parameters physical parameters, cholesterol level, and total protein were estimated. Histopathology studies and triglycerides also were indicative of hepatoprotective property.Conclusion: Finally, the results concluded that the presence of higher amount of Fe and Zn helps to get the significant results of the present investigation which has great impact on liver protection and the selected plant extract showed dose-dependent significant hepatoprotective effect against ethanol-induced hepatotoxicity in Wistar rats.

PROTECTIVE EFFECT OF KADUKKAI MAATHIRAI (TERMINALIA CHEBULA-BASED POLYHERBAL SIDDHA FORMULATION) IN ETHANOL-INDUCED LIVER DISEASE IN RATS

Objective: The objective of this study was to evaluate the prophylactic effect of Kadukkai maathirai (KM) against ethanol-induced hepatotoxicity in rats.Methods: Four groups (n=6) of adult female Sprague–Dawley rats were used. Ethanol was administered in the dose of 45% v/v 15 mL/kg/body weight twice a day for 8 weeks in the study. The four groups were treated orally for 8 weeks with 2% gum acacia (control), ethanol (toxic control), ethanol + KM 72 mg/kg, and ethanol + KM 400 mg/kg, respectively. At the end of 8 weeks, blood was collected by a retro-orbital puncture for the estimation of liver enzymes (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]). The liver was dissected out for histopathology. Using one-way ANOVA and post hoc Tukey’s test, the data were analyzed.Results: There was a significant (p<0.05) decrease in the serum AST and ALT level in rats treated with KM 72 mg/kg as compared to toxic control. Liver parenchyma showed near normal architecture in KM 72 mg/kg-treated group as compared to ethanol-treated group which showed extensive ballooning degeneration of hepatocytes and microvesicular steatosis.Conclusion: KM, in the dose of 72 mg/kg, which is the therapeutic dosage described in Siddha additional literature, exerted hepatoprotective effect against ethanol-induced liver damage in rats.

Modulatory effects of Viola odorata flower and leaf extracts upon oxidative stress-related damage in an experimental model of ethanol-induced hepatotoxicity.

Ethanol is the most widely abused drug in the world and its long-term use induces oxidative stress in the liver tissue. The aim of this study was to evaluate protective effect of Viola odorata against ethanol-induced hepatotoxicity in Wistar rat. Animals were divided into 9 groups as follows: control (normal saline), ethanol (10 mg/kg, intraperitoneally), ethanol with 3 doses (125, 250, and 500 mg/kg) of ethyl acetate flower and leaf extracts, and positive control (vitamin E 80 mg/kg). Animals were gavaged 30 min before ethanol injection for 28 days. Then, animals were killed and the livers were separated. Oxidative stress parameters, including reactive oxygen species, lipid peroxidation, and protein carbonyl as well as glutathione content, were evaluated. Also, histopathological examination was performed and assessment of blood alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and total antioxidant capacity were evaluated. Ethanol significantly increased oxidative stress markers in liver. Interestingly, administration of both extracts significantly decreased oxidative stress markers in liver tissue and biochemical parameters in the plasma. In addition, abnormal pathological features were improved after treatment with flower and leaf extracts. These results suggested that V. odorata can be considered a candidate for improving conditions due to ethanol-induced tissue oxidative damage because of its antioxidant activity.

Can the indicators of chronic ethanol consumption be minimized by a continuous flaxseed intake?

The aim of this study was to evaluate the use of flaxseed in animals subjected to ethanol-induced hepatotoxicity. Twenty-four male rats were divided into four groups (n=6): control group (CG) which received a control diet and water adlibitum; flaxseed group (FG) which received control diet with an addition of 25% flaxseed flour and water adlibitum; ethanol control group (ECG) which received control diet and a solution of 10% ethanol (v/v) as the only liquid source; and ethanol flaxseed group (EFG) which received control diet with an addition of 25% flaxseed flour and a solution of 10% ethanol (v/v) as the only liquid source. The animals were euthanized at 60days, when blood was collected for biochemical analysis and liver was collected for histomorphometric analysis. Rats fed with diets containing flaxseed showed lower values of alkaline phosphatase (P=0.020) and lower concentration of total bilirubin (P=0.006), direct bilirubin (P=0.013) and indirect bilirubin (P=0.018) compared to ECG and EFG. The groups receiving flaxseed diets demonstrated higher expression of superoxide dismutase (SOD) enzyme (P<0.001) than CG and ECG but did not affect thiobarbituric acid (TBARS) expression (P=0.055). Regarding liver analysis, the ECG and EFG showed larger hepatocyte nuclei and paler cytoplasm than the groups who had not received ethanol, and less in fluid accumulation (oedema) in the cytoplasm than was seen in the FG and EFG livers. These latter two groups showed fewer fatty cells than was seen in the groups that had not been given flaxseed, so that the diagnosis of hepatic steatosis was not justified. In conclusion, therefore, this study showed that the indicators of ethanol chronic consumption can be reduced by the introduction of continuous flaxseed dietary intake.

Shanxi aged vinegar prevents alcoholic liver injury by inhibiting CYP2E1 and NADPH oxidase activities

Shanxi aged vinegar (SAV), as a natural functional ingredient, exhibits high antioxidant activities. This study aimed to investigate the protective effects of SAV on ethanol-induced liver injury and elucidate the underlying molecular mechanisms. The results showed that SAV attenuated ethanol-induced hepatotoxicity by restoring cell viability in LO2 cells, relieving the pathological changes in mice livers and reducing elevated liver enzymes. In addition, SAV (2.500 mL/kg b.w.) significantly decreased ethanol-induced reactive oxygen species (ROS) generation, which subsequently inhibited cell apoptosis and malonaldehyde (MDA) levels and reversed depletion of antioxidative defense system in mice livers. Furthermore, SAV ameliorated ethanol-induced oxidative stress and inflammation by down-regulating the expression of cytochrome P450 2E1 (CYP2E1) enzyme and NADPH oxidase. These data suggest that SAV, a health-promoting antioxidant food, exhibits hepatoprotective effects. The hepatoprotective mechanisms of SAV were associated with alleviation of ethanol-induced oxidative stress through inhibiting CYP2E1 enzyme and NADPH oxidase activities.

Substance P blocks ethanol-induced hepatotoxicity

AimsExcessive alcohol consumption induces hepatic injury and promotes lipid accumulation, events involved in the pathogenesis of serious conditions such as alcoholic liver disease (ALD). Thus, protection of hepatocytes against alcohol-induced death is considered to be a critical approach to prevent development of liver disease. Substance P (SP) is capable of promoting cell proliferation and blocking cell death under diverse stresses, leading to beneficial effects in severe diseases, and is therefore likely to have a therapeutic application in hepatic injury. Main methodsTo assess its effects on ethanol-induced hepatic damage in vitro and in vivo, SP was administered to ethanol-treated hepatocytes and a mouse model of this condition, respectively. The effect of SP was assessed based on cell viability, apoptosis, and Akt/GSK-3β signaling, and mouse liver histology and serum biochemical parameters. Key findingsSP was found to prevent hepatocyte death due to ethanol-induced oxidative stress by upregulating Akt/GSK-3β activation in vitro. In vivo, ethanol treatment elevated levels of serum alanine transaminase and also increased the number of apoptotic cell, exhibiting lipid accumulation in liver tissue, effects that were entirely negated by SP treatment. Taken together, our results revealed that SP is able to block hepatic damage due to ethanol-induced oxidative stress and exerts therapeutic effects in liver disease, including ALD. Our findings identify SP treatment as a potential therapy for hepatic damage.

RNA interference against stromal interacting molecule-1 (STIM1) ameliorates ethanol-induced hepatotoxicity

Previously we have demonstrated that stromal interacting molecule-1 (STIM1) was involved in ethanol induced liver injury. However, the exact pathogenic mechanism of STIM1 in alcoholic liver disease (ALD) is still unknown. We constructed plasmid vectors encoding short-hairpin RNA against STIM1 to investigate its role in ALD in the rat liver cell line BRL and in Sprague-Dawley rats. The results showed that STIM1 targeted sh-RNA (Sh-STIM1) significantly ameliorated ethanol-induced BRL cells injury and liver injury in rats with 20 weeks-induced alcoholic liver disease. Inhibition of STIM1 also reduced intracellular calcium ion concentration, reactive oxygen species (ROS) production, lipid peroxidation, NF-kappa B activation and TNF-α production under ethanol exposure. STIM1 may play an important role in the pathogenesis of alcoholic liver disease. Silencing STIM1 may be effective in preventing alcoholic liver disease.

Role of the pregnane X receptor in binge ethanol-induced steatosis and hepatotoxicity.

The pregnane X receptor (PXR, NR1I2) is a xenobiotic-sensing nuclear receptor that defends against toxic agents. We have shown that PXR promotes chronic ethanol (EtOH)-induced steatosis. Therefore, we examined the role of PXR in binge EtOH-induced hepatotoxicity. Male wild type (WT) and Pxr-null mice were orally administered three binge doses of EtOH (4.5 g/kg, every 12 hours) and euthanized four hours after the final dose. Pxr-null mice displayed higher basal mRNA levels of hepatic lipogenic transcription factor sterol regulatory element binding protein 1c (Srebp-1c) and its target stearoyl-CoA desaturase 1 (Scd1) and the lipid peroxide detoxifying aldo-keto reductase 1b7 (Akr1b7) and higher protein levels of EtOH-metabolizing alcohol dehydrogenase 1 (ADH1). In both genotypes, binge EtOH-induced triglyceride accumulation was associated with inhibition of fatty acid β-oxidation and upregulation of Srebp-1c- regulated lipogenic genes and hepatic CYP2E1 protein. Unexpectedly, gene expression of Cyp2b10, a constitutive androstane receptor target gene, implicated in EtOH hepatotoxicity, was PXR-dependent upregulated by binge EtOH. Also, PXR-dependent was the binge EtOH-induced inhibition of hepatic Akr1b8 mRNA, and protein levels of aldehyde dehydrogenase (ALDH) 1A1 and anti-apoptotic Bcl-2, but increased pro-apoptotic Bax protein expression, leading to increases in residual EtOH concentration and the cellular oxidative stress marker, malondialdehyde. In contrast, Pxr-null mice displayed increased Akr1b7 gene and ADH1 protein expression and hypertriglyceridemia following binge EtOH exposure. Taken together, this study demonstrates that PXR ablation prevents EtOH induced upregulation of Cyp2b10 and that PXR potentiates binge EtOH-induced oxidative stress and inhibition of EtOH catabolism, but protects against alcoholic hyperlipidemia.

Kaempferol’s Protective Effect on Ethanol-Induced Mouse Primary Hepatocytes Injury Involved in the Synchronous Inhibition of SP1, Hsp70 and CYP2E1

The mechanism of ethanol-induced hepatotoxicity was complicated, accompanied by the over-expressions of the cytochrome P450 2E1 (CYP2E1), heat shock protein 70 (Hsp70) and the nuclear factor specificity protein 1 (SP1). Kaempferol (Kaem) could protect the ethanol-induced hepatotoxicity likely by inhibiting the CYP2E1 expression and activity. This study investigated the protective mechanism(s) of kaempferol on ethanol-induced toxicity by dynamic alteration of SP1, Hsp70 and CYP2E1 among the nucleus and different organelles in hepatocytes. After ethanol treatment alone and co-incubation hepatocytes with kaempferol, protein levels of CYP2E1, Hsp70, and SP1 were determined in vitro (western blotting and immunofluorescence). Hepatocytes' viability was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) methods. Glutathione (GSH) levels were evaluated for ethanol-induced oxidative stress. In the ethanol-treated hepatocytes, kaempferol decreased protein levels of CYP2E1 in both microsome and mitochondria, cytosolic Hsp70 and SP1 in nuclear and cytosol, and the oxidative stress and increased the cell viability compared to those of ethanol group. Collectively, our findings propose that the protective mechanism of kaempferol is involved in the synchronous, early and persistent inhibitions of mitochondrial and microsomal CYP2E1, cytosolic Hsp70 and nuclear and cytosolic SP1 in mouse primary hepatocytes' injury induced by ethanol.

Quercetin and its metabolites protect hepatocytes against ethanol-induced oxidative stress by activation of Nrf2 and AP-1.

Alcohol-induced liver disease progresses due to increased reactive oxygen species (ROS) and cellular lipid peroxidation. Quercetin is a flavonoid with strong antioxidant and hepatoprotective effects. We investigated whether 3'-O-methyl quercetin (3'MQ) and quercetin-3-O-glucuronide (Q3GA), two metabolites of quercetin, have protective effects against ethanol-induced hepatotoxicity. Cell viability was increased by quercetin, 3'MQ, and Q3GA in HepG2 hepatocarcinoma cells exposed to ethanol. Our results show that this effect was mediated by diminished ROS generation, decreased lipid peroxidation and up-regulation of antioxidant capacity, including glutathione, superoxide dismutase and catalase. Moreover, down-regulated heme oxygenase-1 (HO-1) expression by ethanol was restored by quercetin, 3'MQ, and Q3GA through the activation of nuclear factor E2-related factor 2 and activator protein-1, but not nuclear factor-kappa B. Overall results suggest that 3'MQ, Q3GA, and quercetin attenuate oxidative stress in hepatocytes exposed to ethanol by up-regulating HO-1 expression and can be used as therapeutic agents for ameliorating alcohol-induced liver disease.

HEPATOPROTECTIVE ACTIVITY OF ETHANOLIC EXTRACT OF TERMINALIA CHEBULA FRUIT AGAINST ETHANOL INDUCED HEPATOTOXICITY IN RATS

Objective: The purpose of this study was to evaluate the effect of Terminalia chebula fruit extract on liver antioxidant enzymes in ethanol-induced hepatotoxicity in rats.Method: Rats were divided into six different groups each having six. Group 1 served as a control, Group 2 received 40% ethanol (2 ml/100 g, oral), in sterile water, Groups 4, 5, and 6 served as extract treatment groups and received 50, 100, and 200 mg/kg, orally, ethanolic fruit extract of T. chebula (TCE) and Group 3 served as standard group and received silymarin 25 mg/kg orally. All the treatment protocols followed 21 days, and after which rats were sacrificed, the liver was taken for antioxidant and histological studies, respectively.Results: The ethanol-treated group rats (G2) showed variable decrease in antioxidant parameter (catalase, glutathione, and glutathione reductase) levels. Administration of ethanolic TCE significantly prevented ethanol-induced elevation in the levels of malondialdehyde lipid peroxidation and decreased antioxidant parameters in experimental groups of rats. The effect of extract was compared with a standard drug, silymarin. The changes in antioxidant parameters were supported by histological profile.Conclusion: It is concluded that the ethanolic fruit TCE protects against ethanol-induced oxidative liver injury in rats.

Beneficial effects of rosmarinic acid against alcohol-induced hepatotoxicity in rats.

Alcohol is a severe hepatotoxicant that causes a variety of liver disorders. Rosmarinic acid (RA), a natural phenol, shows some biological activities, including antioxidant and anti-inflammatory effects. We investigated the effects of RA (10 mg/kg) against ethanol-induced oxidative damage and hepatotoxicity in rats. Animals received ethanol (4 g/kg, i.g.) and (or) RA (10 mg/kg, i.g.) daily for 4 weeks. At the end of the treatment period, rats were weighed and use for biochemical, molecular, and histopathological examinations. Ethanol increased hepatic lipid peroxidation (P < 0.001) and decreased hepatic levels of reduced glutathione (P < 0.01), catalase (P < 0.05), and superoxide dismutase (P < 0.001) compared with control group. RA prevented the prooxidant and antioxidant imbalance induced by ethanol in liver. Furthermore, RA ameliorated the increased liver mass, serum levels of ALT, AST, LDH, TNF-α, and IL-6 in ethanol group. Necrosis and infiltration of inflammatory cells in liver parenchyma were attenuated by RA treatment. Our findings showed that RA prevents ethanol-induced oxidant/antioxidant imbalance and liver injury in an experimental model of ethanol-induced hepatotoxicity. Therefore, RA may be a good candidate to protect against ethanol-induced hepatotoxicity; this deserves consideration and further examination.

Hepatoprotective effect of chitosan-caffeic acid conjugate against ethanol-treated mice

The chitosan-caffeic acid (CCA) conjugate shows a hepatoprotective effect against oxidative stress-induced hepatic damage in cultured hepatocytes. The objective of this study is the verification of the hepatoprotective effect of the CCA in vivo against ethanol-induced liver injury in mice. The administration of ethanol resulted in the increase of the serum-aminotransferase activities (AST and ALT), triglycerides, total cholesterol, and lipid peroxidation. The CCA co-administration, however, significantly (p<0.05) ameliorated these serum biomarkers. The antioxidant-enzyme activities in the liver tissue, including those of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), were significantly decreased by a chronic ethanol administration, whereas the hepatic lipid-peroxidation level was increased. Moreover, the chronic ethanol administration elevated the gene expression of pro-inflammatory cytokines such as tumor-necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the liver tissue. The CCA co-administration, however, significantly (p<0.05) increased the activities of the SOD, CAT, and GPx and caused the down-regulation of the TNF-α- and IL-6-gene expressions in the liver tissue. An histopathologic evaluation also supported the hepatoprotective effect of the CCA against ethanol-induced hepatotoxicity in the mice.

Protective role of licochalcone B against ethanol-induced hepatotoxicity through regulation of Erk signaling.

Objective(s):Oxidative stress has been established as a key cause of alcohol-induced hepatotoxicity. Licochalcone B, an extract of licorice root, has shown antioxidative properties. This study was to investigate the effects and mechanisms of licochalcone B in ethanol-induced hepatic injury in an in vitro study.Materials and Methods:An in vitro model of Ethanol-induced cytotoxicity in BRL cells was used in this study. Cell injury was assessed using WST-1 assay and lactate dehydrogenase, alanine transaminase, and aspartate aminotransferase release assay. Cell apoptosis were quantified by flow cytometric analysis. The intracellular oxidative level was evaluated by reactive oxidative species, malondialdehyde and glutathione detection. Furthermore, the expression level of Erk, p-Erk, Nrf-2 were assessed using Western blot.Results:Treatment with ethanol induced marked cell injury and cell apoptosis in BRL cells. Licochalcone B significantly attenuated ethanol-induced cell injury, and inhibited cell apoptosis. Furthermore, licochalcone B significantly inhibited ethanol-induced intracellular oxidative level, upregulated the expression of p-Erk, and promoted nuclear localization of Nrf2. Additionally, this hepatoprotective role was significantly abolished by inhibition of Erk signaling. However, no apparent effects of Erk inhibition were observed on ethanol-induced hepatotoxicity.Conclusion:This study demonstrates that licochalcone B protects hepatocyte from alcohol-induced cell injury, and this hepatoprotective role might be attributable to apoptosis reduction, inhibition of oxidative stress, and upregulation of Erk–Nrf2. Therefore, licochalcone B might possess potential as a novel therapeutic drug candidate for alcohol-related liver disorders.

Atorvastatin attenuates ethanol-induced hepatotoxicity via antioxidant and anti-inflammatory mechanisms.

The aim of this study was to evaluate the role of inflammation and oxidative damage in hepatotoxicity of ethanol. Also we assessed protective effects of atorvastatin against ethanol-induced hepatotoxicity. In this study, the animals were divided into five groups: control, ethanol (10 mg/kg intraperitoneal (i.p.)), ethanol with atorvastatin (10, 20 mg/kg/day, i.p.) and ethanol-vitamin C group which received ethanol (10 mg/kg/day) plus vitamin C (200 mg/kg, i.p.) for 28 consecutive days. Then, the animals were euthanized and liver tissues were separated. Biochemical markers ALT and AST were measured. Moreover, glutathione (GSH) content, lipid peroxidation, protein carbonyl, nitric oxide and tumor necrosis factor-α (TNF-α) were evaluated. The administration of ethanol for 28 days resulted in an increase in liver damage, oxidative stress and inflammatory markers. The atorvastatin was able to prevent the ethanol-induced hepatotoxicity by decreasing the oxidative stress and inflammation processes. Our study showed the critical role of oxidative damage and inflammation in ethanol-induced hepatotoxicity that markedly was inhibited by administration of atorvastatin. Therefore, atorvastatin can be suggested for prevention of ethanol-induced hepatotoxicity.

Polydatin Protects Rat Liver against Ethanol-Induced Injury: Involvement of CYP2E1/ROS/Nrf2 and TLR4/NF-κB p65 Pathway.

Excessive alcohol consumption leads to serious liver injury, associating with oxidative stress and inflammatory response. Previous study has demonstrated that polydatin (PD) exerted antioxidant and anti-inflammatory effects and attenuated ethanol-induced liver damage, but the research remained insufficient. Hence, this experiment aimed to evaluate the hepatoprotective effect and potential mechanisms of PD on ethanol-induced hepatotoxicity. Our results showed that PD pretreatment dramatically decreased the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) in the serum, suppressed the malonaldehyde (MDA) and triglyceride (TG) content and the production of reactive oxygen species (ROS), and enhanced the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), andalcohol dehydrogenase (ADH), and aldehyde dehydrogenase (ALDH), paralleled by an improvement of histopathology alterations. The protective effect of PD against oxidative stress was probably associated with downregulation of cytochrome P450 2E1 (CYP2E1) and upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and its target gene haem oxygenase-1 (HO-1). Moreover, PD inhibited the release of proinflammatory cytokines (TNF-α, IL-1β, and IL-6) via downregulating toll-like receptor 4 (TLR4) and nuclear factor kappa B (NF-κB) p65. To conclude, PD pretreatment protects against ethanol-induced liver injury via suppressing oxidative stress and inflammation.

Effect of metallothionein on ethanol-induced hepatotoxicity in mice

Effect of metallothionein on ethanol-induced hepatotoxicity in mice

Antioxidants of Phyllanthus emblica L. Bark Extract Provide Hepatoprotection against Ethanol-Induced Hepatic Damage: A Comparison with Silymarin.

Phyllanthus emblica L. (amla) has been used in Ayurveda as a potent rasayan for treatment of hepatic disorders. Most of the pharmacological studies, however, are largely focused on PE fruit, while the rest of the parts of PE, particularly, bark, remain underinvestigated. Therefore, we aimed to investigate the protective effect of the hydroalcoholic extract of Phyllanthus emblica bark (PEE) in ethanol-induced hepatotoxicity model in rats. Total phenolic, flavonoid, and tannin content and in vitro antioxidant activities were determined by using H2O2 scavenging and ABTS decolorization assays. Our results showed that PEE was rich in total phenols (99.523 ± 1.91 mg GAE/g), total flavonoids (389.33 ± 1.25 mg quercetin hydrate/g), and total tannins (310 ± 0.21 mg catechin/g), which clearly support its strong antioxidant potential. HPTLC-based quantitative analysis revealed the presence of the potent antioxidants gallic acid (25.05 mg/g) and ellagic acid (13.31 mg/g). Moreover, one-month PEE treatment (500 and 1000 mg/kg, p.o.) followed by 30-day 70% ethanol (10 mL/kg) administration showed hepatoprotection as evidenced by significant restoration of ALT (p < 0.01), AST (p < 0.001), ALP (p < 0.05), and TP (p < 0.001) and further confirmed by liver histopathology. PEE-mediated hepatoprotection could be due to its free radical scavenging and antioxidant activity that may be ascribed to its antioxidant components, namely, ellagic acid and gallic acid. Thus, the results of the present study support the therapeutic claims made in Ayurveda about Phyllanthus emblica.