Prevention Of Alcoholic Liver Disease Research Articles

Ursolic Acid Ameliorates Alcoholic Liver Injury through Attenuating Oxidative Stress-Mediated Ferroptosis and Modulating Gut Microbiota.

Ursolic acid (UA), a triterpenoid found in plants, has many health benefits for liver function. However, understanding how UA intervenes in alcohol-induced ferroptosis remains unclear because of the lack of research. This study explored the protective effects of UA on alcohol-induced liver injury and further elucidated its mechanism of action. Using a mouse model, acute liver injury was induced via high-dose alcohol gavage, and UA's protective effects were assessed by analyzing serum and liver indicators. The results indicated that UA has a significant protective effect against alcohol-induced liver injury in mice. UA significantly decreased serum ALT, AST, TC, and TG levels. Histopathological examination revealed that UA significantly ameliorated liver damage. UA increased ADH, ALDH, and CYP2E1 enzyme expression levels and alleviated alcohol-induced oxidative damage by regulating alcohol metabolism. Moreover, UA increased SOD and GSH-Px levels and lowered the MDA levels in the liver. Furthermore, UA regulated ACC expression by activating the LKB1/AMPK pathway, thereby inhibiting lipid synthesis and peroxidation. UA also upregulated the expression of GPX4 and SLC7A11 in the liver and exerted hepatoprotective effects by inhibiting alcohol-induced ferroptosis. Additionally, 16S rRNA amplicon sequencing showed that excessive alcohol consumption significantly affected the composition of the mouse gut microbiota, with UA intervention proving to be beneficial for improving gut microbiota imbalance. We also validated the protective effects of UA on alcohol-treated HepG2 cells at the cellular level. In summary, these results revealed that UA can alleviate alcoholic liver injury by inhibiting oxidative stress-mediated ferroptosis and regulating gut microbiota. These findings suggest that UA may serve as a functional component in the prevention of alcoholic liver disease.

Exploring the Potential Role of Massa Medicata Fermentata in Alcoholic Liver Injury Disease Based on Network Pharmacology and Animal Experiments.

ALD is a chronic liver disease caused by chronic excessive alcohol consumption, for which there are no drugs with better efficacy. Ancient literature and modern studies have shown that Massa Medicata Fermentata (MMF) has a hangover effect and ameliorates hepatic inflammation, so we believe that MMF has a potential role in the treatment of alcoholic liver disease. UPLC-Q-Orbitrap HRMS was used to characterize the chemical constituents in MMF. The database was utilized to collect targets for the components and diseases, and cross-targeting analysis of the targets was performed. PPI, KEGG, GO enrichment analysis and molecular docking were performed using the core cross-targeting information to preliminarily validate the mechanism of action of MMF on disease. Finally, animal validation was carried out using male KM mice of the alcoholic liver injury model. MMF could play a role in the therapeutic prevention of alcoholic liver disease through the core targets AKT1, TNF, TP53, IL6 and CASP3 to regulate cancer pathways, lipid, and atherosclerosis, targeting IL-17 signaling, TNF signaling pathway, and hepatitis C, which was confirmed by animal pharmacodynamic experiments. This study serves as a rationale to support MMF in the treatment of ALD and meets the urgent need for clinical treatment of ALD. At the same time, it broadens the scope of clinical application of MMF.

Proteomics and network pharmacology of Ganshu Nuodan capsules in the prevention of alcoholic liver disease.

Ganshu Nuodan is a liver-protecting dietary supplement composed of Ganoderma lucidum (G. lucidum) spore powder, Pueraria montana (Lour.) Merr. (P. montana), Salvia miltiorrhiza Bunge (S. miltiorrhiza) and Astragalus membranaceus (Fisch.) Bunge. (A. membranaceus). However, its pharmacodynamic material basis and mechanism of action remain unknown. A mouse model of acute alcohol liver disease (ALD) induced by intragastric administration of 50% alcohol was used to evaluate the hepatoprotective effect of Ganshu Nuodan. The chemical constituents of Ganshu Nuodan were comprehensively identified by UPLC-QTOF/MS, and then its pharmacodynamic material basis and potential mechanism of action were explored by proteomics and network pharmacology. Ganshu Nuodan could ameliorate acute ALD, which is mainly manifested in the significant reduction of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum and malondialdehyde (MDA) content in liver and the remarkably increase of glutathione (GSH) content and superoxide dismutase (SOD) activity in liver. Totally 76 chemical constituents were identified from Ganshu Nuodan by UPLC-QTOF/MS, including 21 quinones, 18 flavonoids, 11 organic acids, 7 terpenoids, 5 ketones, 4 sterols, 3 coumarins and 7 others. Three key signaling pathways were identified via proteomics studies, namely Arachidonic acid metabolism, Retinol metabolism, and HIF-1 signaling pathway respectively. Combined with network pharmacology and molecular docking, six key targets were subsequently obtained, including Ephx2, Lta4h, Map2k1, Stat3, Mtor and Dgat1. Finally, these six key targets and their related components were verified by molecular docking, which could explain the material basis of the hepatoprotective effect of Ganshu Nuodan. Ganshu Nuodan can protect acute alcohol-induced liver injury in mice by inhibiting oxidative stress, lipid accumulation and apoptosis. Our study provides a scientific basis for the hepatoprotective effect of Ganshu Nuodan in acute ALD mice and supports its traditional application.

Targeting Peroxisome Proliferator-Activated Receptor-β/δ (PPARβ/δ) for the Treatment or Prevention of Alcoholic Liver Disease.

Excessive, chronic alcohol consumption can lead to alcoholic liver disease. The etiology of alcoholic liver disease is multifactorial and is influenced by alterations in gene expression and changes in fatty acid metabolism, oxidative stress, and insulin resistance. These events can lead to steatosis, fibrosis, and eventually to cirrhosis and liver cancer. Many of these functions are regulated by peroxisome proliferator-activated receptors (PPARs). Thus, it is not surprising that PPARs can modulate the mechanisms that cause alcoholic liver disease. While the roles of PPARα and PPARγ are clearer, the role of PPARβ/δ in alcoholic liver disease requires further clarification. This review summarizes the current understanding based on recent studies that indicate that PPARβ/δ can likely be targeted for the treatment and/or the prevention of alcoholic liver disease.

Electrolyzed Hydrogen Water Protects against Ethanol-Induced Cytotoxicity by Regulating Aldehyde Metabolism-Associated Enzymes in the Hepatic Cell Line HepG2.

Excessive alcohol consumption can cause multi-systemic diseases. Among them, alcoholic liver disease is the most frequent and serious disease. Electrolytic hydrogen water (EHW) is produced at the cathode during electrolysis of water and contains a large amount of molecular hydrogen and a low content of platinum nanoparticles with alkaline properties. In this study, we found that EHW inhibits ethanol-induced cytotoxicity by decreasing the intracellular acetaldehyde, a toxic substance produced by ethanol degradation, in hepatocyte cell lines HepG2. Analysis of the mechanism of action revealed that EHW inhibits the metabolism of ethanol to acetaldehyde by suppressing alcohol dehydrogenase. EHW also promotes the metabolism of acetaldehyde to acetic acid by activating aldehyde dehydrogenase, which plays to reduce aldehyde toxicity and intracellular reactive oxygen species in HepG2 cells. These functions were correlated with the concentration of molecular hydrogen in EHW, and were abolished by degassing treatment, suggesting that molecular hydrogen may contribute as a functional factor in the suppression of ethanol-induced hepatocellular damage. Furthermore, hydrogen water with high dissolved hydrogen molecule showed the same hepatocellular protective effect against ethanol as the EHW. These results suggest that EHW may be useful in the prevention of alcoholic liver disease.

A New Perspective on Fish Oil: The Prevention of Alcoholic Liver Disease.

The mechanisms of alcoholic liver diseases (ALD) are very complex and interrelated, including abnormal lipid metabolism, oxidative stress, and gut-derived endotoxin pathway. On the other hand, fish oil is rich in n-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which decrease blood triglyceride concentration in hypertriglycemia patients and show protective effects against fatty liver. However, there is limited evidence from studies of the relationship between fish oil and ALD based on the viewpoint of the intestinal integrity and microflora. Therefore, this review discusses the mechanism of amelioration for ALD by fish oil. Based on our previous studies, partial replacement of olive oil by fish oil in alcohol-containing liquid diet ameliorated the liver damage including fatty liver and inflammation in rats. Based on these results, the mechanisms of hepatoprotective effects due to fish oil substitution were discussed in three parts, such as regulating lipid metabolism, decreasing oxidative stress and maintaining intestinal health. First of all, we found that fish oil substitution increased plasma adiponectin levels, and then increasing MCAD and CPT-1 mRNA levels to accelerate fatty acid oxidation in liver, then further prevent ethanol-induced hepatosteatosis in rats with chronic alcohol-feeding. Fish oil replacement also enhanced hepatic autophagy flux, which enhanced lipid degradation, then inhibited lipid accumulation in liver. Secondly, the appreciable proportion of fish oil decreased lipid peroxidation by reducing the protein expression of cytochrome p450 2E1 in chronic alcohol-feeding rats. We also speculated that the appropriate proportion of n-6 and n-3 PUFAs is very important for preventing alcoholic liver disease. At last, substituting fish oil for olive oil normalized the intestinal permeability and fecal microbiota composition, thus providing a low plasma endotoxin level and inflammatory responses, which exert ameliorative effects on ethanol-induced liver injuries in rats.

Alcoholic liver diseases: Disease spectrum, pathophysiology, oxidative stress and role of flavonoids in alcoholic liver injury

An Alcoholic Liver Disease (ALD) has emerged as the serious health problem globally, with high morbidity and mortality rate. Heavy alcohol consumption resulted in broad spectrum of liver diseases ranging from steatosis (alcoholic fatty liver), alcoholic hepatitis (AH), fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). In this review the detailed patho-physiology of the ALD, role of oxidative stress ALD, the mechanism of action of flavonoids with different models used have been explained. Heavy alcohol consumption leads to severe liver diseases, which is demonstrated by increased blood levels of ALT, AST, and/or lactate dehydrogenase (LDH) and accumulation of lipid in the hepatocytes causing steatosis. There are three mechanisms involved in causing of ALD, those are: (a) acetaldehyde toxicity; (b) oxidative stress or generation of ROS; and lastly (c) provocation of the immune response of hepatocytes causing oxidative stress. This shows that oxidative stress is a major cause for ALD, therefore, defence activities against this stress are most vital in the prevention of ALD. Application of antioxidants especially flavonoids signifies a rational curative strategy to prevent and cure liver diseases involving oxidative stress. Flavonoids inhibit ROS formation by regulating glutathione S-transferase, mitochondrial succinoxidase etc. Since lipid peroxidation is a result of oxidative stress, lipids are protected from oxidative damage using flavonoids. Various flavonoids and their mechanism of action have been discussed in this review, formulation of these flavonoids will be highly beneficial for treatment of ALD.

Hepatoprotective Effects of Steamed and Freeze-Dried Mature Silkworm Larval Powder against Ethanol-Induced Fatty Liver Disease in Rats.

Silkworm, Bombyx mori, contains high amounts of beneficial nutrients, including amino acids, proteins, essential minerals, and omega-3 fatty acids. We have previously reported a technique for producing steamed and freeze-dried mature silkworm larval powder (SMSP), which makes it easier to digest mature silkworm. In this study, we investigated the preventive effects of SMSP on alcoholic fatty liver disease and elucidated its mechanism of action. Male Sprague-Dawley rats treated with SMSP (50 mg/kg) or normal diet (AIN-76A) were administered 25% ethanol (3 g/kg body weight) by oral gavage for 4 weeks. SMSP administration for 4 weeks significantly decreased hepatic fat accumulation in ethanol-treated rats by modulating lipogenesis and fatty acid oxidation-related molecules such as sirtuin 1, AMP-activated protein kinase, and acetyl-CoA carboxylase 1. Moreover, SMSP administration significantly diminished the levels of triglyceride in liver tissues by as much as 35%, as well as lowering the serum levels of triglyceride, gamma glutamyl transpeptidase, alanine transaminase, and aspartate aminotransferase in ethanol-treated rats. SMSP supplementation also decreased the pro-inflammatory tumor necrosis factor-alpha and interleukin 1 beta levels and cytochrome P450 2E1 generating oxidative stress. These results suggest that SMSP administration may be possible for the prevention of alcoholic liver disease.

On the Relationship of Socio-Economic Status and Risk Factors for Alcoholic Liver Disease in North China

BACKGROUND: The present article analyses the association between socioeconomic status (includes education, occupation, income and marriage) and alcoholic liver disease (ALD) risk factors (age, gender, obesity, quantity and duration of alcohol intake, alcoholic beverages, drinking patterns) in Taishan area of Shandong province, to provide scientific basis for the prevention of alcoholic liver disease for the people who mostly need it in north China.METHODS: Across-sectional survey of over 18--year-old inhabitants in Shandong Province in 2011 used multistage, randomized clustered sampling to identify 8186 subjects; 7295 (89.12%) of them were interviewed. Questionnaires, designed by co-working of epidemiologists and hepatologists, included demographic characteristics, current medication use, medical history and health-relevant behaviors, i.e. alcohol consumption, dietary habits and physical activities. Anthropometric measurements, biochemical tests and abdominal ultrasonography were carried out. The sample was determined by Chi-square test, covariance analysis and logistic regression analysis.RESULTS: Because of the small number of female drinkers, alcoholic liver disease prevalence of female was obviously lower than that of male, the very study of the male drinkers is more meaningful and can be represent the whole drinkers group to some extent. Among the four socio-economic status (SES) indicators the marriage status seemed to be the most influential factor. People (men or women) without spouse had higher risk of alcoholic liver disease risk factors than those who had spouse. The risk of people who have different occupation is different. The higher education was associated with risk of ALD.CONCLUSION: Marriage status seemed to be the most important measure of the socioeconomic indicators in relation to the alcoholic liver disease risk factors in the study of population. There is obvious relation between occupation status and alcoholic liver disease risk factors in men. The lower occupation had higher alcoholic liver disease risk factors. People with higher income and education had higher levels of drinking risk factors and lower level of obesity risk factors.

Polysaccharide peptides from Coriolus versicolor: A multi-targeted approach for the protection or prevention of alcoholic liver disease

Alcoholic liver disease (ALD) is a major cause of liver-related morbidity and mortality worldwide. In this paper, we investigated the preventive effect of polysaccharide peptide (PSP), isolated from JNPF-CV05 strain of Coriolus versicolor, on alcohol-induced liver injury in mice. Our data demonstrated that PSP supplementation attenuated ethanol-induced aspartate transaminase (ALT), aspartate transaminase (AST), and microscale malondialdehyde (MDA). Pre-treatment with PSP also significantly decreased ethanol-induced plasma levels of total cholesterol (TC), triacylglycerol (TG), and endotoxin concentration. Mechanistically, PSP treatment upregulated ethanol stimulated the hepatic expression of AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC) and peroxisome proliferator–activated receptor α (PPARα) to inhibit hepatic lipid accumulation. In addition, PSP markedly reduced ethanol stimulated inflammation via inhibiting Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4) mediated nuclear transcription factor- kappa B (NF-κB) signaling pathway. In conclusion, PSP is effective in ameliorating ethanol-induced hepatic steatosis and injury through reducing lipid accumulation during the development of fatty liver and alleviating endotoxin-mediated inflammation. Our findings strengthen that PSP has potential as a dietary supplement or prescription for ALD.

Prunus mume Sieb. et Zucc. fruit ameliorates alcoholic liver injury in mice by inhibiting apoptosis and inflammation through oxidative stress

The effects of Prunus mume Sieb. et Zucc. extract (PME) on alcohol-induced liver injury were investigated. These functions of PME were linked to antioxidant activity that suppress lipogenesis in liver tissue, in part inhibiting activation of sterol response element binding protein-1 through ROS-mitogen-activated protein kinase signalling axis, and by suppressing hepatic apoptosis and inflammation through ROS-mediated p53 signalling pathway. Eight compounds and their structures in PME were also identified by LC-MS analysis, and chlorogenic acid (CGA) and neochlorogenic acid (NeoCGA) were validated using standard compounds by HPLC. The effects of CGA against cellular damage caused by alcohol-induced oxidative stress were confirmed using AML-12 cells. CGA significantly inhibited alcohol-induced apoptosis and MAPK activation in the cells. Moreover, antioxidant activities of CGA in the alcohol treatment were demonstrated regarding to cellular redox status and oxidative damage. These studies validated therapeutic value of PME in the prevention of alcoholic liver disease.

Lactobacillus rhamnosus GG supernatant promotes intestinal barrier function, balances Treg and TH17 cells and ameliorates hepatic injury in a mouse model of chronic-binge alcohol feeding.

Impaired intestinal barrier function plays a critical role in alcohol-induced hepatic injury, and the subsequent excessive absorbed endotoxin and bacterial translocation activate the immune response that aggravates the liver injury. Lactobacillus rhamnosus GG supernatant (LGG-s) has been suggested to improve intestinal barrier function and alleviate the liver injury induced by chronic and binge alcohol consumption, but the underlying mechanisms are still not clear. In this study, chronic-binge alcohol fed model was used to determine the effects of LGG-s on the prevention of alcoholic liver disease in C57BL/6 mice and investigate underlying mechanisms. Mice were fed Lieber-DeCarli diet containing 5% alcohol for 10 days, and one dose of alcohol was gavaged on Day 11. In one group, LGG-s was supplemented along with alcohol. Control mice were fed isocaloric diet. Nine hours later the mice were sacrificed for analysis. Chronic-binge alcohol exposure induced an elevation in liver enzymes, steatosis and morphology changes, while LGG-s supplementation attenuated these changes. Treatment with LGG-s significantly improved intestinal barrier function reflected by increased mRNA expression of tight junction (TJ) proteins and villus-crypt histology in ileum, and decreased Escherichia coli (E. coli) protein level in liver. Importantly, flow cytometry analysis showed that alcohol reduced Treg cell population while increased TH17 cell population as well as IL-17 secretion, which was reversed by LGG-s administration. In conclusion, our findings indicate that LGG-s is effective in preventing chronic-binge alcohol exposure-induced liver injury and shed a light on the importance of the balance of Treg and TH17 cells in the role of LGG-s application.

Inhibition of miR122a by Lactobacillus rhamnosus GG Culture Supernatant Increases Intestinal Occludin Expression and Protects Mice from Alcoholic Liver Disease

Alcoholic liver disease (ALD) has a high morbidity and mortality. Chronic alcohol consumption causes disruption of intestinal microflora homeostasis, dysfunction of the intestinal tight junction barrier, increased endotoxemia and eventually liver steatosis/steatohepatitis and injury. Probiotics supernatant supplementation has been shown to be a potential strategy for the treatment and prevention of ALD via restoring epithelial barrier function. Little is known about how probiotic supernatant works to increase intestinal tight junction proteins, thereby contributing to a protective effect in ALD. Here we show that chronic ethanol exposure increases intestinal miR122a expression, which decreases occludin expression leading to increased intestinal permeability, and Lactobacillus rhamnosus GG culture supernatant (LGGs) supplementation decreases ethanol‐elevated miR122a level and attenuates ethanol‐induced liver injury in mice. Similar to the effect of ethanol exposure, overexpression of miR122a in Caco‐2 monolayers markedly decreases occludin protein level. LGGs supplementation functions in intestinal integrity by inhibition of miR122a, leading to occludin restoration in mice exposed to chronic ethanol treatment.

Hepatoprotective potential ofAloe verapolysaccharides against chronic alcohol-induced hepatotoxicity in mice

Aloe vera polysaccharides are reported to exhibit multiple biological effects, including anti-oxidation, anti-inflammation and immune enhancement. However, their influence on alcoholic liver disease (ALD) remains unclear. This study was designed to determine the protective effect of extracted A. vera polysaccharides (AVGP) against ALD in a chronic alcohol-feeding mouse model and investigate the possible underlying mechanisms. Supplementation of AVGP significantly attenuated the levels of serum aminotransferases, lipids and hepatic TG and ameliorated histopathological alterations in the model of ALD. Interestingly, AVGP markedly up-regulated hepatic expression of lipolytic genes (AMPK-α2 and PPAR-α) but had no effect on lipogenic gene expression. AVGP diminished alcohol-dependent oxidative stress partly through a decrease in MDA and increase in GSH and SOD. Alcohol-induced inflammation was also mitigated by AVGP treatment via significant reduction in LPS and TNF-α, down-regulation of TLR-4 and MyD88 and up-regulation of IκB-α. This study clearly showed that AVGP exerts a potent protective effect against chronic alcohol-induced liver injury. Its hepatoprotective effect appears to be associated with its antioxidant capacity and its ability to accelerate lipolysis and inhibit inflammatory response. The results indicate that AVGP could be considered as a potent food supplement in the prevention of ALD.

Curcumin alleviates ethanol-induced hepatocytes oxidative damage involving heme oxygenase-1 induction

Curcumin is the main bioactive constituent derived from the rhizome of turmeric (Curcuma longa Linn.), which has been used traditionally as hepatoprotective agents in ayurvedic and traditional Chinese medicine for centuries. The present study was carried out to demonstrate the potential protective effect of curcumin pretreatment against ethanol-induced hepatocytes oxidative damage, with emphasis on heme oxygenase-1 (HO-1) induction. Rat primary hepatocytes were isolated and treated with ethanol (100mM) and diverse doses of curcumin (0-50 microM), which was pretreated at various time points (0-5h) before ethanol administration. Hepatic enzyme releases in the culture medium and redox status including HO-1 enzyme activity were detected. Ethanol exposure resulted in a sustained malondialdehyde (MDA) elevation, glutathione (GSH) depletion and evident release of cellular lactate dehydrogenase (LDH) and aspartate aminotransferase (AST), which was significantly ameliorated by curcumin pretreatment. In addition, dose- and time-dependent induction of HO-1 was involved in such hepatoprotective effects by curcumin. Curcumin exerts hepatoprotective properties against ethanol involving HO-1 induction, which provide new insights into the pharmacological targets of curcumin in the prevention of alcoholic liver disease.

Lactobacillus GG treatment ameliorates alcohol-induced intestinal oxidative stress, gut leakiness, and liver injury in a rat model of alcoholic steatohepatitis

Because only 30% of alcoholics develop alcoholic liver disease (ALD), a factor other than heavy alcohol consumption must be involved in the development of alcohol-induced liver injury. Animal and human studies suggest that bacterial products, such as endotoxins, are the second key co-factors, and oxidant-mediated gut leakiness is one of the sources of endotoxemia. Probiotics have been used to prevent and treat diseases associated with gut-derived bacterial products and disorders associated with gut leakiness. Indeed, “probiotic” Lactobacillus rhamnosus has been successfully used to treat alcohol-induced liver injury in rats. However, the mechanism of action involved in the potential beneficial effects of L. rhamnosus in alcohol liver injury is not known. We hypothesized that probiotics could preserve normal barrier function in an animal model of ALD by preventing alcohol-induced oxidative stress and thus prevent the development of hyperpermeability and subsequent alcoholic steatohepatitis (ASH). Male Sprague–Dawley rats were gavaged with alcohol twice daily (8 gm/kg) for 10 weeks. In addition, alcoholic rats were also treated with once daily gavage of either 2.5 × 10 7 live L. rhamnosus Gorbach–Goldin (LGG) or vehicle (V). Intestinal permeability (baseline and at 10 weeks) was determined using a sugar bolus and GC analysis of urinary sugars. Intestinal and liver tissues were analyzed for markers of oxidative stress and inflammation. In addition, livers were assessed histologically for severity of ASH and total fat (steatosis). Alcohol + LGG (ALC + LGG)–fed rats had significantly ( P ≤ .05) less severe ASH than ALC + V–fed rats. L. rhamnosus Gorbach–Goldin also reduced alcohol-induced gut leakiness and significantly blunted alcohol-induced oxidative stress and inflammation in both intestine and the liver. L. rhamnosus Gorbach–Goldin probiotic gavage significantly ameliorated ASH in rats. This improvement was associated with reduced markers of intestinal and liver oxidative stress and inflammation and preserved gut barrier function. Our study provides a scientific rationale to test probiotics for treatment and/or prevention of alcoholic liver disease in man.

Nutrition and alcoholic liver disease

Summary Mounting interest in the potential value of nutritional therapy in the treatment of alcoholic liver disease (ALD) has arisen as a result of the growing body of evidence implicating nutritional intervention as a key player in ameliorating ALD. This review will focus on the involvement of nutrition in the pathogenesis of ALD, with extended focus on the role of micronutrients in the intervention or prevention of ALD. Oxidative damage is a major pathway in the initiation of ALD, and as such, many micronutrients have protective roles owing to their antioxidant properties. This can be either a direct action by scavenging free radicals or an indirect one elicited by increasing the synthesis or recycling of glutathione, the main intracellular antioxidant molecule. Micronutrients should be consumed as part of an energy‐sufficient (at least 1400 kcal/day), macronutrient‐based diet, as ALD progresses more quickly in people who have substituted a normal diet with alcohol, as opposed to those who drink alcohol in addition to their daily diet. Discontinuing alcohol consumption will enhance recovery, although this is not always possible with alcohol‐addicted patients. In conclusion, an energy‐sufficient diet high in vitamins and minerals will help protect against the formation and progression of ALD. However, alcohol abstinence is the recommended course of action to aid any recovery.

Vitamin- E For Treatment Of Early Stages Of Ethanol Induced Liver Damage

The association of alcohol abuse and liver damage was known from ancient times. No systematic studies have been carried out to evaluate the role of Vitamin-E or the drug in the prevention of alcoholic liver disease. So it was considered worthwhile to study the role of Vitamin E for the treatment of alcohol induced fatty liver. ABBREVIATIONS gm gram TG triglyceride

Iron chelators and iron toxicity

Iron chelation may offer new approaches to the treatment and prevention of alcoholic liver disease. With chronic excess, either iron or alcohol alone may individually injure the liver and other organs. In combination, each exaggerates the adverse effects of the other. In alcoholic liver disease, both iron and alcohol contribute to the production of hepatic fibrosis through their effects on damaged hepatocytes, hepatic macrophages, hepatic stellate cells, and the extracellular matrix. The pivotal role of iron in these processes suggests that chelating iron may offer a new approach to arresting or ameliorating liver injury. For the past four decades, deferoxamine B mesylate has been the only iron-chelating agent generally available for clinical use. Clinical experience with deferoxamine has demonstrated the safety and effectiveness of iron chelation for the prevention and treatment of iron overload. Determined efforts to develop alternative agents have at last resulted in the development of a variety of candidate iron chelators that are now in or near clinical trial, including (a) the hexadentate phenolic aminocarboxylate HBED [ N, N′-bis(2-hydroxybenzyl)ethylenediamine- N, N′-diacetic acid], (b) the tridentate desferrithiocin derivative 4′-OH-dadmDFT [4′-hydroxy-( S)-desazadesmethyl-desferrithiocin; ( S)-4,5-dihydro-2-(2,4-dihydroxyphenyl)-4-thiazolecarboxylic acid], (c) the tridentate triazole ICL670A [CGP72 670A; 4-[3,5-bis-(hydroxyphenyl)-1,2,4-triazol-1-yl]-benzoic acid], and (d) the bidentate hydroxypyridin-4-one deferiprone [L1, CP20; 1,2-dimethyl-3-hydroxypyridin-4-one]. These agents may provide new pharmacological means of averting or ameliorating liver damage in alcoholic liver disease by binding, inactivating, and eliminating the reactive forms of iron that contribute to oxidative injury of cellular components, are involved in signal transduction, or both.

Dilinoleoylphosphatidylcholine Decreases Ethanol-Induced Cytochrome P4502E1

Cytochrome P4502E1 (CYP2E1) induction by ethanol contributes to alcoholic liver disease and we found that a mixture of polyunsaturated phosphatidylcholines (PPC), which protects against alcohol-induced liver injury, also decreases CYP2E1. Since dilinoleoylphosphatidylcholine (DLPC) is the major component of PPC, we assessed here whether it is responsible for the protection of PPC by feeding rats for 8 weeks our liquid diet containing ethanol (36% of energy) or isocaloric carbohydrates, with either DLPC (1.5 g/1000 cal), PPC (3 g/1000 cal), or linoleate. CYP2E1 was assessed by Western blots and by two of its enzyme activities: the microsomal ethanol-oxidizing system (MEOS) and p-nitrophenolhydroxylase (PNP). With ethanol, CYP2E1 increased 10-fold, with corresponding rises in PNP and MEOS activities. Compared to linoleate, DLPC significantly decreased cytochrome b5, total cytochromes P450, CYP2E1 content and its corresponding activities. DLPC decreases ethanol-induced CYP2E1 and should be considered for the prevention of alcoholic liver disease.