Chronic Alcohol-induced Liver Injury Research Articles

Xie Zhuo Tiao Zhi formula ameliorates chronic alcohol-induced liver injury in mice.

This study aimed to evaluate the protective role and potential mechanisms of Xie Zhuo Tiao Zhi decoction (XZTZ) on alcohol-associated liver disease (ALD). XZTZ significantly alleviated alcohol-induced liver dysfunction, based on histological examinations and biochemical parameters after 4-week administration. Mechanically, alcohol-stimulated hepatic oxidative stress was ameliorated by XZTZ, accompanied by the improvement of Nrf2/Keap1 expression and alcohol-activated phosphorylation of pro-inflammatory transcription factors, including JNK, P38, P65, and IκBα, were rescued by XZTZ. In conclusion, XZTZ demonstrates potential in alleviating alcohol-induced liver injury, oxidative stress, and inflammation possibly through modulation of Nrf2/Keap1 and MAPKs/NF-κB signaling pathways, suggesting its potential as a therapeutic option for patients with alcoholic liver disease.

Deletion of Mixed Lineage Kinase Domain Like Pseudokinase Aggravates Chronic Alcohol-Induced Liver Injury via Increasing Apoptosis.

he mixed lineage kinase domain like pseudokinase (MLKL) is known to play a protective role in non-alcoholic fatty liver disease (NAFLD) via inhibition of necroptosis pathway. However, the role of MLKL in alcoholic liver disease (ALD) is not yet clear. C57BL/6N wild-type (WT) and MLKL-knockout (KO) mice (8-10weeks old) were randomly divided into eight groups. To establish ALD model of different durations, ethanol (EtOH) was fed to WT and MLKL KO for 10days, 4weeks, and 8weeks. The control group was fed with Lieber-DeCarli control diet for 8weeks. Mortality, degree of hepatic inflammation, and steatosis were compared among the groups. Bulk mRNA transcriptome analysis was performed. Abundance of transcript and gene expressions were calculated based on read count or Transcript by Million (TPM) value. Survival rate of MLKL KO mice compared to WT was similar until 4weeks, but the survival of MLKL KO mice significantly decreased after 8weeks in ALD model. There was no difference in degree of inflammation, steatosis, and NAS scores between EtOH-fed MLKL KO and EtOH-fed WT mice at 10days. However, at 4weeks and 8weeks, the degree of hepatic steatosis, NAS, and inflammation were increased in MLKL KO mice. RNA transcriptome data showed that fatty acid synthesis, and lipogenesis, mitochondria, and apoptosis-related pathways were upregulated in EtOH-fed MLKL KO mice compared to EtOH-fed WT mice. Although hepatocyte apoptosis (BAX/BCL2 ratio, caspase-3, and TUNEL staining) increased after EtOH intake; however, apoptosis was more significantly increased in EtOH-fed MLKL KO mice compared to the WT group. At the same time, hepatic cFLIP was decreased in EtOH-fed MLKL KO mice compared to the WT group. MLKL deletion did not prevent chronic alcohol-induced liver damage independently of necroptosis and exacerbated hepatic steatosis by increasing hepatocyte apoptosis.

Bioactive peptides as a novel strategy to prevent alcoholic liver injury.

Alcohol intake has become one of the leading risks to human health and wellness, among which acute and/or chronic alcohol-induced liver injury is a leading threaten, with few therapeutic options other than abstinence. In recent years, studies suggested that certain bioactive peptides from food sources could represent natural and safe alternatives for the prevention of alcoholic liver injury. Hence, this chapter focus on the advanced research on bioactive peptides exerting hepatoprotective activity against alcoholic liver injury. The main sources of protein, strategies for the preparation of hepatoprotective hydrolysates and peptides, underlying mechanisms of peptides on hepatoprotection, and possible structure-activity relationship between peptides and hepatoprotective activity were summarized and discussed, aiming to give a systematic insight into the research progress of hepatoprotective peptides. However, more efforts would be needed to give a clearer insight into the underlying mechanisms and structure-activity relationship before using hepatoprotective peptides as functional food ingredients or dietary supplements.

Protection of Inonotus hispidus (Bull.) P. Karst. against Chronic Alcohol-Induced Liver Injury in Mice via Its Relieving Inflammation Response.

Alcoholic liver disease (ALD) can be induced by excessive alcohol consumption, and has a worldwide age-standardized incidence rate (ASIR) of approximately 5.243%. Inonotus hispidus (Bull.) P. Karst. (IH) is a mushroom with pharmacological effects. In ALD mice, the hepatoprotective effects of IH were investigated. IH strongly ameliorated alcohol-induced pathological changes in the liver, including liver structures and its function-related indices. Intestinal microbiota and serum metabolomics analysis showed that IH altered the associated anti-inflammatory microbiota and metabolites. According to results obtained from Western blot, immunohistochemistry (IHC), and enzyme-linked immunosorbent assay (ELISA), IH downregulated the levels of pro-inflammation factors interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α), enhanced the expressions of peroxisome proliferator-activated receptor alpha (PPARα) and 15-hydroxprostaglandin dehydrogenase (15-PGDH), and inhibited the phosphorylated activation of Janus kinase (JAK) 1 and signal transducer and activator of transcription (STAT) 3, confirming the hepatoprotection of IH against alcohol damage via anti-inflammation. This study provides the experimental evidence for the hepatoprotective effects of IH in chronic ALD.

WED-435 - Deletion of mixed lineage kinase domain like pseudokinase aggravate chronic alcohol induced liver injury via increasing apoptosis

WED-435 - Deletion of mixed lineage kinase domain like pseudokinase aggravate chronic alcohol induced liver injury via increasing apoptosis

Fermented Gold Kiwi Prevents and Attenuates Chronic Alcohol-Induced Liver Injury in Mice via Suppression of Inflammatory Responses

Excessive alcohol consumption increases the risk of liver disease and liver-related death. Ninety percent of alcohol consumed is broken down in the liver; excessive consumption destroys liver cells and causes stress. The gold kiwi contains more vitamin C than the green kiwi, and various studies have reported that the gold kiwi boosts digestive health. Fermented gold kiwi (FGK) was made using two lactic acids. It contains many more bioactive compounds than fresh gold kiwi. Mice were first given FGK (50, 125, and 250 mg/kg b.w.) and then given a 5 g/kg alcohol solution (50% w/v) for 2 weeks. The results indicate that the FGK promoted hepatic function by significantly decreasing the serum ethanol and aldehyde levels and downgrading the serum TC and TG levels. The FGK attenuated alcohol-induced oxidative stress and improved alcohol metabolism by controlling the ADH and ALDH levels in murine liver tissue. In addition, the FGK significantly reduced the concentration of inflammatory cytokines (TNF-α, IL-1β, and IL-6) in mouse serum and liver tissue. The overexpression of inflammatory mediators (iNOS, COX-2) was also decreased in the FGK groups. This study demonstrates that FGK exerts a protective effect against alcohol-induced liver damage by improving alcohol metabolism and increasing anti-inflammatory activity. This finding suggests that FGK might be developed into a functional food treatment against alcohol-induced liver disease.

Monounsaturated fatty acid-enriched olive oil exacerbates chronic alcohol-induced hepatic steatosis and liver injury in C57BL/6J mice.

Dietary oil composition determines the pathological processes of alcoholic fatty liver disease (AFLD). Oil rich in saturated fatty acids protects, whereas oil rich in polyunsaturated fatty acids aggravates the alcohol-induced liver injury. However, limited studies have been conducted to address how monounsaturated fatty acids (MUFAs) enriched oil controls the pathological development of AFLD. Therefore, this study was designed to evaluate the effect of MUFA-enriched extra virgin olive oil (OO) on AFLD. Twenty C57BL/6J mice were randomly allocated into four groups and fed modified Lieber-DeCarli liquid diets containing isocaloric maltose dextrin a non-alcohol or alcohol with corn oil and OO for four weeks. Dietary OO significantly exacerbated alcohol-induced liver dysfunction, evidenced by histological examinations and disturbed biochemical parameters. Dietary OO with alcohol decreased hormone-sensitive lipase (HSL), phosphorylated 5'-AMP-activated protein kinase (p-AMPK), and carnitine palmitoyltransferase-Iα (CPT1α) expression, and increased sterol regulatory element-binding protein-1c (SREBP-1c), diacylglycerol acyltransferase-2 (DGAT2), and very low-density lipoprotein receptor (VLDLR) expression in the liver. It also promoted the expression of hepatic interleukin-6 (IL-6) and hepatic tumour necrosis factor-alpha (TNF-α) at the transcriptional level. Additionally, adipose tissue lipolysis partially had an etiologic effect on alcohol-induced hepatic steatosis under OO pretreatment. In conclusion, MUFA-enriched OO exacerbated liver dysfunction in vivo. OO should be cautiously considered as a unique dietary oil source for individuals with AFLD.

Transcriptome Analysis of Hepatoprotection of Traditional Medicines Against Acute CCl4 and Chronic Alcohol-Induced Liver Injury in Mice

Hua-Feng-Dan produced adaptive mechanisms in the liver to render it to tolerant to CCl4-induced oxidative stress stimuli. Thus, transcriptome analysis is a powerful tool to reveal the molecular mechanisms of hepatoprotection by traditional medicines.

Structure and hepatoprotective activity of Usp10/NF-κB/Nrf2 pathway-related Morchella esculenta polysaccharide

The water-soluble Morchella esculenta polysaccharide 2 (MEP2) was purified and isolated from an aqueous extract of the Morchella esculenta fruiting bodies. MEP2, having a molecular weight of 959 kDa, has a →4)-α-D-Glcp-(1→ glucan backbone, and this branch was substituted at the H-6 position by an α-D-Glcp-(1 → 4)-α-D-Glcp-(1→ residue and an α-D-Glcp-(1→ residue. The hepatoprotective activity and potential mechanism of action of MEP2 were also investigated. MEP2 ameliorated severe liver damage and regulated the liver function indicators and the alcohol-related enzyme levels in chronic alcohol-induced mice. Combined with biochemical detection, the gut microbiota, metabolites, and proteomics results revealed that MEP2 regulates the levels of hepatic cytokines related to inflammatory response and oxidative stress, as well as those of intestinal Bacteroides, Oscillospira, Parabacteroides, Alistipes, and Prevotella, through the ubiquitin-specific peptidase 10 (Usp10)/nuclear factor κB (NF-κB)/nuclear factor erythroid-2 related factor 2 (Nrf2) signaling pathway in the liver of mice induced by long-term alcohol intake. These data provide experimental evidence for the application of MEP2 in chronic alcohol-induced liver injury.

Oyster protein hydrolysates alleviated chronic alcohol-induced liver injury in mice by regulating hepatic lipid metabolism and inflammation response

The oyster protein hydrolysate (OPH) possesses various biological activities that have the potential to ameliorate alcoholic liver disease (ALD). This study aimed to assess the protective effects of OPH on liver injury in mice induced by chronic alcohol treatment and the underlying mechanism was further explored by transcriptome and proteome from a global view. Compared with the Model group, OPH treatment significantly decreased the liver weight (p < 0.01) and reduced the content of liver injury markers alanine aminotransferase (ALT, by 34.14%, p < 0.01), aspartate aminotransferase (AST, by 35.31%, p < 0.01) and alkaline phosphatase (ALP, by 17.18%, p < 0.05) while increased the content of hepatic function marker total protein (TP, by 17.30%, p < 0.05) in serum. Meanwhile, only mild hepatocyte injury accompanied by less lipid droplet accumulation was observed in OPH treated ALD mice. The transcriptome and proteome results indicated that 482 target genes and 111 target proteins were involved in the ameliorative effect of OPH on ALD. After data integration, 43 co-regulated targets were identified, which were mainly related to lipid metabolism (reduction of cholesterol and triglyceride accumulation) and inflammatory response [inhibition of inflammatory responses through toll-like receptors (TLRs), nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs), and tumor necrosis factor (TNF) signaling pathways]. Consistent with omics data, the hepatic levels of total lipid, total cholesterol, triglyceride, interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), and transforming growth factor β (TGF-β) were declined by OPH treatment in ALD mice. Collectively, our results prove that OPH possesses potent hepatoprotective activities and has the potential to be used as a novel functional ingredient for the management of ALD.

Rumex hanus by. Extract Protects Against Chronic Alcohol-Induced Liver Injury in Mice.

Alcoholic liver disease (ALD) has become a global health problem. The hepatoprotective effects of bioactive ingredients extracted from Rumex hanus by. on chronic alcoholic liver injury was investigated for the first time. The extract from R. hanus by. (ERHB) was obtained by 70% ethanol extraction, and the endotoxin antagonism rate of ERHB was 88.94 ± 1.24% in vitro. The animal experiments demonstrated that ERHB promoted hepatic function by significantly enhancing the activities of alcohol dehydrogenase and acetaldehyde dehydrogenase, and by reducing the activities of cytochrome P450 proteins, alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase. Furthermore, ERHB improved alcohol-induced dyslipidemia by regulating lipid metabolism. In addition, ERHB ameliorated the alcohol-induced liver injury by inhibiting endotoxin-caused inflammation. Seven compounds with antagonistic activity on endotoxin were identified in ERHB. These results demonstrated that ERHB had protective effects on ALD and if the results can be confirmed in humans, it might be useful as a functional food supplement for ALD treatment.

The amelioration of alcohol-induced liver and intestinal barrier injury by Lactobacillus rhamnosus Gorbach-Goldin (LGG) is dependent on Interleukin 22 (IL-22) expression

ABSTRACT Alcoholic liver disease (ALD) is a common clinical liver injury disease. Lactobacillus rhamnosus Gorbach-Goldin (LGG) has been revealed to alleviate alcohol-induced intestinal barrier and liver injury. However, the underlying mechanism of LGG treatment for ALD remains unclear. To clarify this aspect, a chronic plus binge ALD model was constructed using C57BL/6 mice in line with a chronic alcohol binge feeding protocol. Interleukin 22 (IL-22) level was determined by quantitative real-time polymerase-chain reaction and enzyme-linked immunosorbent assays. Effects of LGG in model or IL-22 knockdown in LGG-treated model on the liver injury and steatosis status, as well as intestinal barrier function were assessed by hematoxylin eosin (HE) staining. Levels of alanine aminotransferase (ALT), triglyceride (TG), and aspartate aminotransferase (AST) in serum were measured by the corresponding kit. Western blot analysis was conducted to detect protein expressions of intestinal tight junction protein 1 (ZO-1) and Claudin-1. Concretely, LGG elevated IL-22 level in liver tissues and serum, while inhibiting ALT, TG, and AST levels in alcohol-exposed mice. Moreover, LGG alleviated liver injury, steatosis, and intestinal barrier injury caused by alcohol, and enhanced ZO-1 and Claudin-1 expressions. Furthermore, IL-22 knockdown increased ALT, TG, and AST levels in serum, and aggravated liver injury, steatosis, and intestinal barrier injury. ZO-1 and Claudin-1 levels were downregulated by IL-22 silencing. Importantly, downregulation of IL-22 reversed the effect of LGG on the liver and intestinal barrier injury. To conclude, LGG protects against chronic alcohol-induced intestinal and liver injury via regulating the intestinal IL-22 signaling pathway.

Lactobacillus plantarum ZY08 relieves chronic alcohol-induced hepatic steatosis and liver injury in mice via restoring intestinal flora homeostasis

This present study was designed to test the protective role of two Lactobacillus plantarum strains, E680 and ZY08, against alcoholic liver disease (ALD) in C57BL/6 mice. The ALD mouse model was established by exposing the mice to a Lieber-DeCarli ethanol liquid diet. The two probiotic strains (109 cfu/day) were administered by oral gavage, respectively. Our data showed that L. plantarum ZY08, but not E680, intervention significantly mitigated alcohol-related hepatic steatosis, liver injury, intestinal barrier, and it alleviated plasma endotoxin (LPS) levels, and affected hepatic genes relating to lipid metabolism. Furthermore, Lactobacillus plantarum ZY08 effectively restored intestinal flora homeostasis via recovering flora abundance, including Blautia, Oscillibacter, Lachnoclostridium and Intestimonas, and consequently elevated intestinalshort-chain fatty acid (SCFA) content. More importantly, removing intestinal microorganisms through ABX gavage markedly abolished the beneficial aspects of Lactobacillus plantarum ZY08, indicating that the regulative role of Lactobacillus plantarum ZY08 contributed to its protective role against ALD. Overall, Lactobacillus plantarum ZY08 is a potential candidate for mitigating alcohol-induced hepatic steatosis and liver injury.

Alternative activation of macrophages by prostacyclin synthase ameliorates alcohol induced liver injury

Alcoholic liver disease (ALD) is a major cause of chronic liver disease worldwide. Macrophages exhibit different functional states and are classified as classically activated (M1) and alternatively activated (M2) macrophages. However, the mechanisms that govern M1/M2 polarization in chronic ALD remain to be elucidated. Prostacyclin (PGI2) synthase (PTGIS) is an enzyme of the prostaglandin pathway which catalyzes the conversion of Prostaglandin H2 (PGH2) to PGI2. PTGIS has anti-inflammatory properties. However, the function of PTGIS in ALD has not yet been determined. In this study, we demonstrated that PTGIS was downregulated in ALD and forced PTGIS expression in vivo using recombinant adeno-associated viral vector-packed PTGIS overexpression plasmid, which alleviated the inflammatory response and suppressed the macrophage M1 phenotype in mice. Loss- and gain-of function-experiments demonstrated that forced PTGIS expression inhibited the macrophage switch to the M1 phenotype and promoted M2 polarization. Furthermore, we identified the genes regulated by PTGIS through RNA-sequencing (RNA-seq) analysis. Gene ontology and KEGG pathway analyses showed that PTGIS regulates many genes involved in the immune response and is enriched in the Janus kinase/signal transducers and activators of transcription (JAK/STAT) signal transduction pathway, which plays an important role in regulating macrophage polarization. The proteins interacting with JAKs were predicted using the STRING database. The overlap between the RNA-seq and the STRING database was interleukin-6; this indicated that it was involved in macrophage polarization regulated by JAK/STAT signaling. We further explored the microRNAs that could regulate the expression of PTGIS through TargetScan. The results of luciferase assay illustrated that the expression of PTGIS was regulated by miR-140-3p.1. These results imply that PTGIS plays a pivotal role in ALD, partly by influencing macrophage polarization.Prostacyclin synthase (PTGIS) levels are decreased by elevated miR-140-3p.1 expression in chronic alcoholic liver disease. Inducing PTGIS expression alleviates chronic alcohol-induced liver injury by promoting macrophage M2 polarization and inhibiting the M1 phenotype through the JAK/STAT pathway. Interestingly, inducing PTGIS expression also increases IL-6 expression, which has not yet been explained.

Multi-omics integration reveals the hepatoprotective mechanisms of ursolic acid intake against chronic alcohol consumption.

Alcoholic liver disease (ALD) is a major health issue globally. In addition to pharmacotherapy, dietary support is also regarded as reliable strategy for ALD management. As a widely distributed natural constituent within edible plants, the present study aims to investigate the hepatoprotective effects of ursolic acid (UA) against ALD and also to deepen insights into the underlying targets and mechanisms comprehensively. The hepatoprotective activity of UA against chronic alcohol-induced liver injury was investigated on Lieber-DeCarli liquid diet-based mouse model. In-depth RNA-seq transcriptomics and TMT-based proteomics analyses were conducted in parallel. Data integration as well as bioinformatics analysis were also performed to unravel the targets and mechanisms associated with the hepatoprotective activity of UA intake against alcoholic liver injury comprehensively. The serum biomarkers and pathological characteristics indicated the hepatoprotective effects of UA intake on alcoholic liver injury. 567 target genes and 377 target proteins related to the hepatoprotective activity of UA were identified in transcriptomics and proteomics analysis respectively, most of which were associated with function of cellular process, cell part and binding. After data integration, 56 co-regulated targets, including ADH4, CYP450 enzymes, NQO1, apolipoproteins, glutathione-S-transferase, etc. which were consistently modulated on both mRNA and protein levels were identified. These co-regulated targets were found to be correlated with 70 KEGG pathways led by carcinogenesis, retinol metabolism and CYP450 metabolism pathways. UA intake ameliorated chronic alcohol-induced liver injury. Given the role of the co-regulated targets in ALD and the bioinformatics analysis results, CYP450-, glutathione and redox homeostasis-dependent antioxidation, promotion of lipid transport, and restoration of ethanol metabolic capacity are the potentially underlying mechanisms. This information will further deepen our insights into the hepatoprotective effects of UA-rich edible plants, and provide us valuable instruction for ALD management.

The triterpenoids-enriched extracts from Antrodia cinnamomea mycelia attenuate alcohol-induced chronic liver injury via suppression lipid accumulation in C57BL/6 mice

The major pathologic hallmark of the alcoholic liver disease (ALD) is the representation of chronic alcohol-induced hepatocyte lipid accumulation. This study aims to investigate the hepatoprotective role of triterpenoids-enriched extracts from Antrodia cinnamomea mycelia (ACT) in chronic alcohol-induced liver injury mice, establishing in C57BL/6 mice through gradient alcohol feeding for 24 weeks. In long-term alcohol consumption mice, the significantly lost body weight, increased organ indexes, hepatic alanine aminotransferase and aspartate aminotransferase levels were all remissed after 6-week ACT orally administration, showing its hepatoprotective property. ACT suppressed the triglyceride, total cholesterol and low-density lipoprotein levels, and enhanced high-density lipoprotein levels in serum or/and liver of chronic alcohol damaged mice. Combining with the pathological observations, ACT displayed an anti-steatosis effects to restrain the progress of ALD. Based on proteomic analysis and enzyme-linked immunosorbent assay, ACT had been confirmed to regulate the levels of lipid biogeneration-related factors and depressed the over-accumulation of hepatic reactive oxygen species. According to further data, ACT prevented alcoholic liver injury may be associated with mediating lipid metabolism-related to PGC-1α and NF-κB signaling. In summary, ACT protected the body against chronic alcohol ingest induced liver injury through its regulation lipid on metabolism.

Gut dysbiosis correction contributes to the hepatoprotective effects of Thymus quinquecostatus Celak extract against alcohol through the gut-liver axis.

Alcoholic liver disease (ALD) is a major health issue globally due to the consumption of alcoholic beverages. Thymus quinquecostatus Celak is a food additive and an edible herb that is widely used in Asia and possesses hepatoprotective activity, but the underlying mechanisms behind this protective activity are not completely understood. The purpose of this study was to investigate the hepatoprotective effects of Thymus quinquecostatus Celak extract (TQE) against ALD as well as the underlying mechanism based on gut microbiota and the gut-liver axis. TQE supplementation markedly alleviated chronic alcohol-induced liver injury in C57 mice. TQE also ameliorated gut barrier dysfunction induced by alcohol. Consequently, the activation of the lipopolysaccharide (LPS) translocation-mediated TLR4 pathway and the subsequent inflammatory response and ROS overproduction in the liver were suppressed. Meanwhile, alcohol-induced gut microbiota dysbiosis was also corrected by TQE. To further investigate the contribution of gut dysbiosis correction to the beneficial effects of TQE on ALD, a fecal microbiota transplantation study was conducted. TQE-manipulated gut microbiota transplantation markedly counteracted the alcohol-induced gut dysbiosis in the recipient mice. In parallel with gut dysbiosis correction, liver damage was partly ameliorated in the recipient mice. Gut barrier dysfunction, endotoxemia, TLR4 pathway induction as well as downstream inflammatory response and ROS overproduction were also partly suppressed due to gut dysbiosis correction in alcohol-fed recipient mice. In summary, these results suggest that gut dysbiosis correction contributes to the hepatoprotective effects of TQE against alcohol through the gut-liver axis.

Sasa quelpaertensis Nakai ethyl acetate fraction protects the liver against chronic alcohol-induced liver injury and fat accumulation in mice

Sasa quelpaertensis Nakai ethyl acetate fraction protects the liver against chronic alcohol-induced liver injury and fat accumulation in mice

Puerarin Exerts the Hepatoprotection from Chronic Alcohol-Induced Liver Injury via Inhibiting the Cyclooxygenase-2 and the 5-Lipoxygenase Pathway in Rats

Background: Puerarin (PR) as one of the main ingredients of the root of the traditional herb Kudzu has been suggested to improve chronic alcohol-induced liver injury. We explore the specific mechanisms of PR on hepatocellular changes after administration of alcohol. Methods: Sprague-Dawley rats were treated with 55% alcohol for 12 weeks to induce a chronic alcoholic liver damage model. Then the rats in each group were administered by oral gavage with zileuton, celecoxib, and PR for 2 weeks, respectively. Results: In the PR group, the weight loss was markedly improved and the abnormal serum alanine aminotransferase and aspartate aminotransferase were significantly lowered after PR treatment when compared to the alcoholic liver injured model group. Pathological examination indicated that alcohol-induced hepatocellular injury was improved by the PR treatment. The 5-lipoxygenase (5-Lox) and cyclooxygenase-2 (Cox-2) at the protein level and the mRNA level were obviously downregulated accompanied with the PR treatment. Meanwhile, the peroxisome proliferator-activated receptor γ (PPAR-γ) at the protein and mRNA level was notably elevated and the tumor necrosis factor α at the protein and mRNA level was markedly decreased following the PR treatment. Conclusion: The possible cytoprotective mechanisms of PR may be involved inhibition of the Cox-2 pathway and the 5-Lox pathway to suppress inflammatory response and regulate the protective factor PPAR-γ expression.

Vitamin D Deficiency Aggravates Hepatic Oxidative Stress and Inflammation during Chronic Alcohol-Induced Liver Injury in Mice.

Vitamin D deficiency has been reported in alcoholics. This study is aimed at evaluating the effects of vitamin D deficiency on chronic alcohol-induced liver injury in mice. Mice were fed with modified Lieber-DeCarli liquid diets for 6 weeks to establish an animal model of chronic alcohol-induced liver injury. In the VDD+EtOH group, mice were fed with modified diets, in which vitamin D was depleted. Vitamin D deficiency aggravated alcohol-induced liver injury. Furthermore, vitamin D deficiency aggravated hepatocyte apoptosis during alcohol-induced liver injury. Although it has a little effect on hepatic TG content, vitamin D deficiency promoted alcohol-induced hepatic GSH depletion and lipid peroxidation. Further analysis showed that vitamin D deficiency further increased alcohol-induced upregulation of hepatic inducible nitric oxide synthase (inos), two NADPH oxidase subunits p47phox and gp91phox, and heme oxygenase- (HO-) 1. By contrast, vitamin D deficiency attenuated alcohol-induced upregulation of hepatic antioxidant enzyme genes, such as superoxide dismutase (sod) 1 and gshpx. In addition, vitamin D deficiency significantly elevated alcohol-induced upregulation of hepatic proinflammatory cytokines and chemokines. Taken together, these results suggest that vitamin D deficiency aggravates hepatic oxidative stress and inflammation during chronic alcohol-induced liver injury.