Alcoholic Damage Research Articles

Potential Targets for the Protective Effect of Astaxanthin on Ethanolinduced Damage in Rat Liver Mitochondria.

Alcohol intoxication leads to multiple degenerative disorders in the structure and function of mitochondria. The mechanisms underlying these disorders, as well as ways to prevent them, are an urgent task in biomedicine. We investigate the mechanism of the positive effect of AX on rat liver mitochondria after chronic alcohol administration and suggest the targets of its effects. In this work, we continued our studies of astaxanthin (AX) as a possible protector of mitochondria from the toxic effects of ethanol. In our experiments, we used the Lieber-DeCarly model of chronic alcohol intoxication, which allows high-dose alcohol intake. Four groups of animals were used in the experiments: group 1 (control), group 2 (treated with AX), group 3 (treated with ethanol), and group 4 (treated with ethanol and AX together). Rat liver mitochondria (RLM) were isolated by the standard method modified in our laboratory. A multifunctional chamber with built-in electrodes was used to determine mitochondrial functions. Electrophoresis followed by Western blot analysis was used to detect mitochondrial proteins. Statistical significance was calculated using t-test Student-Newman- Keuls test. AX has been shown to have a positive effect on the functioning of the mitochondrial permeability transition pore (mPTP), the regulation of signaling pathways, as well as mitochondrial dynamics. It was found that AX is able to suppress the degenerative effect of alcohol on liver mitochondria. Targets for the protective action of AX in rat liver mitochondria (RLM) have been proposed. The discovered protective effect of AX on liver mitochondria during alcohol damage may contribute to the development of new strategies for the treatment of alcohol- induced damage.

Effects of fish oil on insulin resistance in the brains of rats with alcoholic liver damage

This study was to examine the effects of fish oil on alcoholic brain damage in rats, focusing on the insulin signaling pathway. Thirty-six male Wistar rats were divided into control (Lieber-DeCarli control liquid diet), CF25 (control diet + 25 % fish oil substitution), CF57 (control diet + 57 % fish oil substitution), E (Lieber-DeCarli ethanol liquid diet), EF25 (ethanol diet + 25 % fish oil substitution), and EF57 (ethanol diet + 57 % fish oil substitution) groups. The behavioral test was also conducted. After 8 weeks, the E group exhibited brain damage, including nuclear-condensed pyramidal cells and positivity for ionized calcium-binding adaptor molecule 1 (Iba-1) antibody. The E group revealed the higher hippocampal insulin receptor substrate-1 (IRS-1) and hypothalamic glycogen synthase kinase 3β (GSK3β), while presented the lower hepatic IRS-1, hippocampal insulin-like growth factor-1 (IGF-1) receptor and glucose transporter 4 (GLUT4). After fish oil substitution, the brain nuclear condensation was attenuated and the hippocampal IRS-1 and hypothalamic GSK3β were significantly decreased.

A highly sensitive and specific fluorescent probe for detecting ONOO– in liver-injured cells and tissues

The liver is a vital organ in the human body that performs important physiological functions. During the damage process, the liver produces a large amount of ONOO–, which is difficult to directly capture and detect in the physiological environment. Therefore, this work introduced the design and synthesis of HN-ONOO, a novel naphthylimide-based fluorescent probe, aiming to dynamically monitor the changes of ONOO– during liver damage. HN-ONOO demonstrated a stable response to ONOO–, achieving quantitative detection. Since the high biocompatibility of HN-ONOO, we observed different degrees of up-regulation of ONOO– in the liver inflammation damage, alcohol damage, drug damage, fat accumulation model, and mice drug-damaged livers. These results suggest that HN-ONOO can recognize and detect the liver injury marker ONOO–. In addition, HN-ONOO, as a powerful tool for early detection of liver damage and detoxification research, provides a new approach for related research.

Synthesis and antimicrobial activity testing of quaternary ammonium silane compounds

With increasing health awareness of the pathogenic effects of disease-causing microorganisms, interest in and use (of medical textiles, disinfectants in medical devices, etc.) of antimicrobial substances have increased in various applications, such as medical textiles and disinfectants (alcohol-based and nonalcoholic), in medical devices There are several concerns with alcohol-based disinfectants, such as surface deformation of medical devices due to high alcohol content and damage to skin tissue caused by lipid and protein denaturation of cell membranes. Quaternary ammonium compounds (quats) were preferred because they have the potential to prepare water-based disinfectants. In this study, novel (3-chloropropyl)triethoxysilane (CPTMO) and (3-chloropropyl)triethoxysilane (CPTEO) based quaternary ammonium silane compounds (silane-quats) were developed using quats with carbon chain lengths of C12, C14, C16 and C18. Titration (ASTM D2074) was used to calculate the yield of the synthesis and the structures of the products were characterised by Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (13C NMR, 1H NMR) and gas chromatography-mass spectrometry (GC–MS).The in vitro antimicrobial activity of the synthesized samples was evaluated against Gram-positive (Staphylococcus aureus (S. aureus), Enterococcus hirae (E. hirae)) and Gram-negative (Escherichia coli (E. coli), Pseudomonas aeruginosa (P. aeruginosa)) bacteria and fungi (Candida albicans (C. albicans), Aspergillus brasiliensis (A. brasiliensis)) using the minimum inhibitory concentration (MIC) test. According to MIC tests, the silane-quats with the highest antimicrobial effects were dimethylhexadecyl[3-(trimethoxysilyl)propyl]ammonium chloride (SQ3), which had an MIC of < 16 μg/ml (ppm) against E. coli, S. aureus, E. hirae, C. albicans, and A. brasiliensis and 32 μg/ml against P. aeruginosa. The MIC test results also showed antimicrobial activity at least 2 times greater than that of the commercially available disinfectant benzalkonium chloride (BAC). Findings suggest that SQ3 (C16) holds promise as an effective medical disinfectant, presenting a novel approach to combating microbial infections in healthcare settings.

Acute alcoholic hepatitis – the role of modern hepatoprotectors

Alcoholic hepatitis is a progressive inflammatory-dystrophic lesion of the liver, the pathogenetic mechanism of which is based on alcoholic damage. Acute alcoholic hepatitis is defined primarily as an exacerbation of the chronic process of alcoholic liver disease. Two mechanisms are defined as the basis for the formation of alcohol-associated liver damage: primary (direct effect of ethanol on hepatocytes and oxidative stress provoked by it) and secondary (through changes in the gut-liver axis with dysbacteriosis and increased permeability of the intestinal wall). For the treatment of acute alcoholic hepatitis, mainly glucocorticosteroids are used, the action of which is directed at cytotoxic and inflammatory mechanisms of the pathogenesis of this disease. Also, phosphodiesterase inhibitors, broad-spectrum antibiotics (rifaximin), probiotics, prebiotics, synbiotics, enterosorbents and hepatoprotectors are actively used. Choosing a hepatoprotector that is effective and safe for patients is still a challenge. At the moment one of the most promising and optimal in terms of “price-quality” ratio drug from this group is a domestic drug from the group of combined hepatoprotectors – Remaxol (inosine + meglumine + methionine + nicotinamide + succinic acid). A clinical case of application of this drug in a patient diagnosed with acute alcoholic hepatitis combined with chronic alcoholic hepatopathy is presented. Not severe course (MELD: 16. Maddrey’s index: 14.04). Ademetionine was prescribed. On the background of the prescribed treatment slight improvements were noted, no significant changes in laboratory data were registered (MELD: 16, Maddrey index: 12.54). After replacement of the hepatoprotector by Remaxol, the following was observed: correction of the general condition, correction of the mental status, reduction of the severity of hepatosplenomegaly, normalization of laboratory parameters (MELD: 10. Maddrey’s index: 6.06). Based on the review of Russian and foreign literature, as well as personal experience in the use of Remaxol, we can conclude that this pharmacological agent contributes to a more favorable course of acute alcoholic hepatitis, a significant reduction in the risk of complications, as well as reducing the length of hospital stay and the cost of treatment.

Alcohol Triggers the Accumulation of Oxidatively Damaged Proteins in Neuronal Cells and Tissues.

Alcohol is toxic to neurons and can trigger alcohol-related brain damage, neuronal loss, and cognitive decline. Neuronal cells may be vulnerable to alcohol toxicity and damage from oxidative stress after differentiation. To consider this further, the toxicity of alcohol to undifferentiated SH-SY5Y cells was compared with that of cells that had been acutely differentiated. Cells were exposed to alcohol over a concentration range of 0-200 mM for up to 24 h and alcohol effects on cell viability were evaluated via MTT and LDH assays. Effects on mitochondrial morphology were examined via transmission electron microscopy, and mitochondrial functionality was examined using measurements of ATP and the production of reactive oxygen species (ROS). Alcohol reduced cell viability and depleted ATP levels in a concentration- and exposure duration-dependent manner, with undifferentiated cells more vulnerable to toxicity. Alcohol exposure resulted in neurite retraction, altered mitochondrial morphology, and increased the levels of ROS in proportion to alcohol concentration; these peaked after 3 and 6 h exposures and were significantly higher in differentiated cells. Protein carbonyl content (PCC) lagged behind ROS production and peaked after 12 and 24 h, increasing in proportion to alcohol concentration, with higher levels in differentiated cells. Carbonylated proteins were characterised by their denatured molecular weights and overlapped with those from adult post-mortem brain tissue, with levels of PCC higher in alcoholic subjects than matched controls. Hence, alcohol can potentially trigger cell and tissue damage from oxidative stress and the accumulation of oxidatively damaged proteins.

Морфофункциональная характеристика печени и поджелудочной железы при воздействии гепатопротектора Ремаксол на фоне острого алкогольного воздействия у крыс

Purpose of the study. To study the effect of hepatoprotective drug Remaxol on morphology of the liver and pancreas as well as on biochemical indices of blood serum in rats with alcohol damage. Material and methods. The study was carried out on sexually mature male white laboratory rats divided into three groups: 1st control group – intact animals (2 rats); 2nd – experimental animals (5 rats), on which acute pancreatitis on the background of alcohol poisoning was modeled by daily administration of 40% aqueous ethanol solution at a dose of 5 mg/kg weight for 7 days without treatment; 3rd – experimental group (5 rats) with alcohol exposure and with administration of Remaxol at a dose of 5 mg/kg weight daily for another 7 days. Morphological study of the liver, its macrostructure was carried out, diameters of hepatocytes and pancreatic acinuses in animals of experimental and control groups were measured, biochemical parameters were estimated. Results. Blood tests indicate acute alcohol poisoning in the experimental groups; short-term (7 days) alcohol damage has less effect on the size of hepatocytes than on the size of pancreatic acini; pancreatic acini were more reactive to the toxic effect of alcohol; against the background of insignificant morphometric differences, the morphological signs of cells and organs changed; in the liver and pancreas there were signs of inflammatory (swelling of cells in the liver and pancreas). Conclusion. Histological picture of the liver and pancreas of animals with acute alcohol damage against the background of Remaxol treatment showed a decrease in the toxic effect of 40% alcohol on hepatocytes and pancreatocytes, normalization of their morphological parameters.

Morphofunctional characteristics of the liver and pancreas under the influence of the hepatoprotector “Remaxol” against the background of acute alcohol damage in rats

The goal. To study the effect of hepatoprotective drug “Remaxol” on morphology of the liver and pancreas as well as on blood serum indices in rats with alcohol damage. Materials and Methods. The study was conducted on mature male white laboratory rats divided into three groups: the first (control group) - intact animals, the second and third (experimental groups) - daily part of the rats received 40 % aqueous ethanol solution (96 % ethanol in a dose of 8ml/kg weight) for 7 days, then part of the rats from the experimental group were injected “Remaxol” in a dose 5 mg/kg weight daily for 7 days. Morphological study of the liver and its macrostructure was carried out; diameters of hepatocytes, sinusoid capillaries and pancreatic acini in animals of the control and experimental groups were measured; general and biochemical blood parameters were assessed. Results. Blood tests demonstrated acute alcohol poisoning in experimental groups (leukocytosis); short-term (7 days) alcohol damage had less effect on the size of hepatocytes than on the size of pancreatic acini; pancreatic acini were more reactive on toxic influence of alcohol; in the liver and pancreas there were signs of inflammatory reaction (cell swelling, lymphocytes infiltration). Conclusion. Histological picture of the liver and pancreas of the animals with acute alcohol poisoning on the background of “Remaxol” treatment showed a decrease in the toxic effect of 40 % alcohol on hepatocytes and pancreatocytes, normalization of their morphological parameters.

Alcohol and e-cigarette damage alveolar-epithelial barrier by activation of P2X7r and provoke brain endothelial injury via extracellular vesicles

BackgroundUse of nicotine containing products like electronic cigarettes (e-Cig) and alcohol are associated with mitochondrial membrane depolarization, resulting in the extracellular release of ATP, and mitochondrial DNA (mtDNA), mediating inflammatory responses. While nicotine effects on lungs is well-known, chronic alcohol (ETH) exposure also weakens lung immune responses and cause inflammation. Extracellular ATP (eATP) released by inflammatory/stressed cells stimulate purinergic P2X7 receptors (P2X7r) activation in adjacent cells. We hypothesized that injury caused by alcohol and e-Cig to pulmonary alveolar epithelial cells (hPAEpiC) promote the release of eATP, mtDNA and P2X7r in circulation. This induces a paracrine signaling communication either directly or via EVs to affect brain cells (human brain endothelial cells - hBMVEC).MethodsWe used a model of primary human pulmonary alveolar epithelial cells (hPAEpiC) and exposed the cells to 100 mM ethanol (ETH), 100 µM acetaldehyde (ALD), or e-Cig (1.75 µg/mL of 1.8% or 0% nicotine) conditioned media, and measured the mitochondrial efficiency using Agilent Seahorse machine. Gene expression was measured by Taqman RT-qPCR and digital PCR. hPAEpiC-EVs were extracted from culture supernatant and characterized by flow cytometric analysis. Calcium (Ca2+) and eATP levels were quantified using commercial kits. To study intercellular communication via paracrine signaling or by EVs, we stimulated hBMVECs with hPAEpiC cell culture medium conditioned with ETH, ALD or e-cig or hPAEpiC-EVs and measured Ca2+ levels.ResultsETH, ALD, or e-Cig (1.8% nicotine) stimulation depleted the mitochondrial spare respiration capacity in hPAEpiC. We observed increased expression of P2X7r and TRPV1 genes (3-6-fold) and increased intracellular Ca2+ accumulation (20-30-fold increase) in hPAEpiC, resulting in greater expression of endoplasmic reticulum (ER) stress markers. hPAEpiC stimulated by ETH, ALD, and e-Cig conditioned media shed more EVs with larger particle sizes, carrying higher amounts of eATP and mtDNA. ETH, ALD and e-Cig (1.8% nicotine) exposure also increased the P2X7r shedding in media and via EVs. hPAEpiC-EVs carrying P2X7r and eATP cargo triggered paracrine signaling in human brain microvascular endothelial cells (BMVECs) and increased Ca2+ levels. P2X7r inhibition by A804598 compound normalized mitochondrial spare respiration, reduced ER stress and diminished EV release, thus protecting the BBB function.ConclusionAbusive drugs like ETH and e-Cig promote mitochondrial and endoplasmic reticulum stress in hPAEpiC and disrupts the cell functions via P2X7 receptor signaling. EVs released by lung epithelial cells against ETH/e-cig insults, carry a cargo of secondary messengers that stimulate brain cells via paracrine signals.

Histologic changes in the liver and kidney tissues of rats with acute alcohol injury and metabolic correction

Annotation. The liver and kidneys are among the organs that often suffer from the toxic effects of ethanol. The issue of drug correction of alcoholic organ damage, and in particular the role of H2S, remains insufficiently studied. The aim of the study was to evaluate the role of quercetin, hydrogen sulphide donor NaHS and their combination in the correction of morphological changes in the liver and kidneys of rats with acute alcohol injury (AAI). The study was conducted on 25 white male rats weighing 120-130 g, divided into five groups (5 rats in each group). Animals of groups 2-5 were modelled with AAI by intragastric administration of 40% ethanol at a dose of 20 ml/kg for 7 days. In order to correct the AAI, animals of group 3 were administered quercetin (100 mg/kg, intraperitoneally, once/day, for 7 days), group 4 – the hydrogen sulphide donor NaHS-H2O (3 mg/kg, intraperitoneally, once/day, for 7 days), group 5 – both quercetin and NaHS-H2O in the above doses. Animals of group 1 (control) received an equivalent amount of solvents. Histological examinations were performed according to conventional methods. It has been established that in the liver of rats with AAI there are disturbances in the lobular structure, radial ordering of the hepatic beams, signs of inflammation, hypertrophy and fatty infiltration of hepatocytes. In the kidneys, signs of renal glomerular fragmentation, vascular glomerular compaction, tubular epithelial dystrophy, and inflammation are found. Some improvements in the histological structure of the liver and kidneys were observed with quercetin, but they were inferior to those observed with NaHS. Combined therapy with quercetin and NaHS was most effective in restoring the normal structure of the liver and kidneys of rats: the radial arrangement of hepatic beams was restored, the nuclear cytoplasmic index increased, signs of fatty degeneration of hepatocytes and renal epithelial dystrophy decreased, and the activity of the inflammatory response in the organs decreased. The obtained results histologically confirm the feasibility of using hydrogen sulphide donors to enhance the hepatoprotective and nephroprotective effects of quercetin in the setting of AAI.

Effect of Purple Sweet Potato Using Different Cooking Methods on Cytoprotection against Ethanol-Induced Oxidative Damage through Nrf2 Activation in HepG2 Cells.

The aim of this study was to investigate the effects of different cooking methods on the hepatoprotective effects of purple sweet potatoes against alcohol-induced damage in HepG2 cells. Purple sweet potatoes (Ipomeoea batatas L. Danjami) were subjected to different cooking methods, including steaming, roasting, and microwaving. Steaming resulted in a higher cytoprotective effect against alcohol damage than the other cooking methods. Additionally, the highest inhibition of glutathione depletion and production of reactive oxygen species against alcohol-induced stress were observed in raw and/or steamed purple sweet potatoes. Compared to roasted and/or microwaved samples, steamed samples significantly increased the expression of NADPH quinone oxidoreductase 1, heme oxygenase 1, and gamma glutamate-cysteine ligase in alcohol-stimulated HepG2 cells via the activation of nuclear factor erythroid 2-related factor 2. Moreover, ten anthocyanins were detected in the raw samples, whereas five, two, and two anthocyanins were found in the steamed, roasted, and microwaved samples, respectively. Taken together, steaming purple sweet potatoes could be an effective cooking method to protect hepatocytes against alcohol consumption. These results provide useful information for improving the bioactive properties of purple sweet potatoes using different cooking methods.

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.

Oral Probiotic Expressing Human Ethanol Dehydrogenase Attenuates Damage Caused by Acute Alcohol Consumption in Mice.

Alcohol is an essential drug in human life with multiple medical functions, but excessive alcohol intake, even a single episode of binge drinking, can cause serious damage. Reducing alcohol consumption or absorption is a direct way to alleviate the related harm. Alcohol is decomposed successively by alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) in the liver. Here, we produced a human ADH1B (hADH1B)-expressing probiotic, a recombinant Lactococcus lactis, that aimed to enhance alcohol degradation in the intestinal tract after oral administration. Our results showed that the oral hADH1B-expressing probiotic reduced alcohol absorption, prolonged the alcohol tolerance time, and shortened the recovery time after acute alcohol challenge. More importantly, the liver and intestine were protected from acute injury caused by alcohol challenge. Therefore, the engineered probiotic has the potential to protect organ damage from alcohol consumption. Furthermore, this engineered probiotic may have beneficial effects on alcohol-related diseases such as alcoholic fatty liver disease. IMPORTANCE Alcohol plays an important role in medical treatment, culture, and social interaction. However, excessive alcohol consumption or improper alcohol intake patterns can lead to serious damage to health. Aiming to reduce the harm of alcohol consumption, we designed a recombinant probiotic expressing hADH1B. Our results showed that this recombinant probiotic can reduce alcohol absorption and protect the body from alcohol damage, including hangover, liver, and intestinal damage. Reducing alcohol damage is helpful to the health of people with difficulty in abstinence. The engineered probiotic may provide new strategies for treatment and prevention of the negative effects of alcohol, and it also has the potential for widespread application.

Medication overuse headache and substance use disorder: A comparison based on basic research and neuroimaging.

It has yet to be determined whether medication overuse headache (MOH) is an independent disorder or a combination of primary headache and substance addiction. To further explore the causes of MOH, we compared MOH with substance use disorder (SUD) in terms of the brain regions involved to draw more targeted conclusions. In this review, we selected alcohol use disorder (AUD) as a representative SUD and compared MOH and AUD from two aspects of neuroimaging and basic research. We found that in neuroimaging studies, there were many overlaps between AUD and MOH in the reward circuit, but the extensive cerebral cortex damage in AUD was more serious than that in MOH. This difference was considered to reflect the sensitivity of the cortex structure to alcohol damage. In future research, we will focus on the central amygdala (CeA), prefrontal cortex (PFC), orbital-frontal cortex (OFC), hippocampus, and other brain regions for interventions, which may have unexpected benefits for addiction and headache symptoms in MOH patients.

Dynamics of pathomorphological changes in the liver of rats at different stages of experimental alcohol damage

Liver diseases represent one of the most common problems in gastroenterology. The liver, as the most important organ of metabolism, which plays a major role in anabolic and energy processes, takes part in the adaptive and compensatory reactions of the body under exogenous and endogenous adverse influences. Individual factors play a major role in the development of this disease, one of which is the duration of the effect of alcohol on the body. The duration of alcohol consumption affects the morpho-functional properties of the liver. When alcohol was given to the research animals, hypertrophic changes were seen in the linear dimensions of hepatocytes: in the 12th week of alcoholization, the nuclear area was 1.25 times larger, and the cytoplasmic area of hepatocytes was 1.16 times larger compared with the same indicators in the 6th week of alcoholization. Alcoholic hepatitis is characterized by protein-fatty degeneration, inflammatory lymphocytic infiltration, increase in the area of sinusoids and the size of hepatocytes, and, accordingly, the Vizotto coefficient (1.83 times in the 6th week and 2.10 times in the 12th week of the research). The alcohol consumption is accompanied by increase in the volume of the nucleus and cytoplasm of hepatocytes, decrease in the nuclear-cytoplasmic ratio with increase in pathohistological changes. With the lengthening of the terms of alcoholization, the number of binuclear hepatocytes decreased. Morphometric calculation of the number of fat cells per 100 hepatocytes showed that in the 12th week of the experiment, the number of fatty inclusions increased by 1.42 times, compared with 6 weeks of forced alcoholization. Fatty small- and large-droplet steatosis of hepatocytes was diffuse in nature. The duration of alcoholization also affects the liver vessels. The diameter of the central vein in the 6th week of the experiment was 1.52 times greater than in control rats, and 1.81 times in the 12th week of alcoholization. The bile ducts of rats of the experimental groups were also larger in diameter: by 37% after 6 weeks and 47% after 12 weeks of forced alcoholization. An increase in the area of the sinusoids and the diameter of the central vein indicates an impairment of the blood supply to the liver. The complexity of the structure of the liver and the diversity of its functions necessitate the use of a variety of diagnostic techniques and methodological approaches to assessing its activity in the normal condition, during a pathology. It will be promising to study the structure of the liver at the ultramicroscopic level of the effect of drugs on the treatment of alcoholic liver disease during different periods of alcoholization.

Butyrate ameliorates chronic alcoholic central nervous damage by suppressing microglia-mediated neuroinflammation and modulating the microbiome-gut-brain axis

BackgroundAlcohol abuse triggers neuroinflammation, leading to neuronal damage and further memory and cognitive impairment. Few satisfactory advances have been made in the management of alcoholic central nervous impairment. Therefore, novel and more practical treatment options are urgently needed. Butyrate, a crucial metabolite of short-chain fatty acids (SCFAs), has been increasingly demonstrated to protect against numerous metabolic diseases. However, the impact of butyrate on chronic alcohol consumption-induced central nervous system (CNS) lesions remains unknown. MethodsIn this study, we assessed the possible effects and underlying mechanisms of butyrate on the attenuation of alcohol-induced CNS injury in mice. Firstly, sixty female C57BL/6 J mice were randomly divided into 4 groups: pair-fed (PF) group (PF/CON), alcohol-fed (AF) group (AF/CON), PF with sodium butyrate (NaB) group (PF/NaB) and AF with NaB group (AF/NaB). Each group was fed a modified Lieber-DeCarli liquid diet with or without alcohol. After six weeks of feeding, the mice were euthanized and the associated indicators were investigated. ResultsAs indicated by the behavioral tests and brain morphology, dietary NaB administration significantly ameliorated aberrant behaviors, including locomotor hypoactivity, anxiety disorder, depressive behavior, impaired learning, spatial recognition memory, and effectively reduced chronic alcoholic central nervous system damage. To further understand the underlying mechanisms, microglia-mediated inflammation and the associated M1/M2 polarization were measured separately. Firstly, pro-inflammatory TNF-α, IL-1β, and IL-6 in brain and peripheral blood circulation were decreased, but IL-10 were increased in the AF/NaB group compared with the AF/CON group. Consistently, the abnormal proportions of activated and resting microglial cells in the hippocampus and cortex regions after excessive alcohol consumption were significantly reduced with NaB treatment. Moreover, the rectification of microglia polarization (M1/M2) imbalance was found after NaB administration via binding GPR109A, up-regulating the expression of PPAR-γ and down-regulating TLR4/NF-κB activation. In addition to the direct suppression of neuroinflammation, intriguingly, dietary NaB intervention remarkably increased the levels of intestinal tight junction protein occludin and gut morphological barrier, attenuated the levels of serum lipopolysaccharide (LPS) and dysbiosis of gut microbiota, suggesting that NaB supplementation effectively improved the integrity and permeability of gut microecology. Finally, the neurotransmitters including differential Tryptophan (Trp) and Kynurenine (Kyn) were found with dietary NaB administration, which showed significantly altered and closely correlated with the gut microbiota composition, demonstrating the complex interactions in the microbiome-gut-brain axis involved in the efficacy of dietary NaB therapy for alcoholic CNS lesions. ConclusionDietary microbial metabolite butyrate supplementation ameliorates chronic alcoholic central nervous damage and improves related memory and cognitive functions through suppressing microglia-mediated neuroinflammation by GPR109A/PPAR-γ/TLR4-NF-κB signaling pathway and modulating microbiota−gut−brain axis.

Вплив поліфенолів на пероксидне окиснення ліпідів та антиоксидантну систему в піднижньощелепних слинних залозах при поєднаному введенні алкоголю та ліпополісахариду S. typhi

The purpose of the study was to study the effect of polyphenols (curcumin, epigallocatechin-3-gallate, and quercetin) on indicators of lipid peroxidation and antioxidant protection in the submandibular salivary glands of rats with alcohol damage against the background of lipopolysaccharide-induced systemic inflammatory response. Materials and methods. The studies were conducted on 35 rats of the Wistar line weighing 205–220 g, divided into 5 groups of seven animals in each: the 1st group (control) included animals receiving isotonic sodium chloride solution intragastrically twice a day; the 2nd group included rats exposed to alcohol (in a dose of 24 mg/kg intragastrically through gavage twice a day) for last 2 weeks during lipopolysaccharide-induced systemic inflammatory response; the rats of the 3rd, 4th and 5th groups were exposed to alcohol during lipopolysaccharide-induced systemic inflammatory response, which also received polyphenols, administered intragastrically: curcumin (diferuloylmethane, in a daily dose of 200 mg/kg), epigallocatechin-3-gallate (in a daily dose of 40 mg/kg), quercetin (in a daily dose of 200 mg/kg), respectively. The level of lipid peroxidation in the tissues of the submandibular salivary glands was assessed by the formation of compounds that react with thiobarbituric acid. The state of antioxidant protection was assessed by the increase in the concentration of thiobarbituric acid-active products during a 1.5-hour incubation in iron ascorbate buffer solution, as well as by the activity of superoxide dismutase. Results and discussion. When using curcumin under the experimental conditions, the concentration of thiobarbituric acid-reactants in the homogenate of submandibular salivary glands before and after incubation was 59.3 and 55.7% inferior to the corresponding results of the 2nd group, when prescribing epigallocatechin-3-gallate – by 55.7 and 51.2%, quercetin – by 67.0 and 61.0%, respectively. This was accompanied by a probable increase in the activity of superoxide dismutase in the tissues of the submandibular salivary glands. Conclusion. The use of curcumin and bioflavonoids (epigallocatechin-3-gallate and quercetin) under conditions of combined administration of 40% ethanol and S. typhi lipopolysaccharide significantly limits the development of lipid peroxidation in the tissues of the submandibular salivary glands, increases their antioxidant potential, superoxide dismutase activity

Prevalence of non-alcoholic fatty liver disease in apparently healthy blood bank donors: metabolic, alcohol, and combined damage

Prevalence of non-alcoholic fatty liver disease in apparently healthy blood bank donors: metabolic, alcohol, and combined damage

Hovenia acerba Lindl. peduncles and seeds extracts ameliorate alcoholic liver injury by activating the Nrf2/HO-1 signalling pathway in LO2 cells and mice

Hovenia acerba Lindl. (HA) was formerly used as a treatment for alcohol overdosing. To explore the mechanism of hepatoprotective effect of HA, the chemical components of Hovenia acerba Lindl. peduncles extract (HAPE) and Hovenia acerba Lindl. seeds extract (HASE) were compared by UPLC-QTOF-MS. Moreover, the alcohol damage model of human normal hepatocytes (LO2) and male Kunming mice were used to measure their effects on alcoholic liver damage. Results showed that HASE had 32 kinds of phenolic compounds, and the main components were caffeic acid, vitexin-2″-O-glucoside, ferulic acid hexoside, quercetin and its glycosides; HAPE had 24 kinds of phenolic compounds, and the main components were caffeic acid, kaempferol and chrysophano. The phenolic content of HASE (151.73 ± 12.66 mg gallic acid equivalent per gram of dry weight) (mg GAE/g DW) was higher than that of HAPE (17.89 ± 1.59 mg GAE/g DW). HASE and HAPE could increase the LO2 cell viability in the alcohol damage models. Moreover, the levels of triacylglycerol (TG), total cholesterol (TC), alanine aminotransferase(ALT), and aspartate aminotransferase (AST) were decreased, the activities of superoxide dismutase (SOD) and catalase (CAT) were increased, and the concentration of malondialdehyde (MDA) was decreased in both HASE and HAPE treated cell and mice groups. Results also showed that the concentration of reduced glutathione (GSH) and the activity of glutathione peroxidase (GSH-Px) were increased in mice. HASE and HAPE raised the mRNA expressions of nuclear factor erythroid-2 related factor 2 (Nrf2) and activated antioxidant-related genes: heme oxygenase-1 (HO-1), NADPH quinone acceptor oxidoreductase 1 (NQO1), and glutamate-cysteine ligase modifier subunit (GCLM), and enhanced the expression of Nrf2 and HO-1 proteins. HASE and HAPE could also increase antioxidant activity by enhancing Nrf2-mediated inducible expression of HO-1 to protect hepatocytes from injury. Furthermore, HASE showed better liver protective effect than HAPE. This study demonstrated the protective benefits of Hovenia acerba Lindl. peduncles and seeds extracts on alcoholic liver injury.

Chemical structure and protective effect against alcoholic kidney and heart damages of a novel polysaccharide from Piperis Dahongpao

In this manuscript, the polysaccharide isolated from Piperis Dahongpao was extracted with the method of water-extraction and alcohol-precipitation. Besides, the homogeneous polysaccharide (PDP-1) with an MW of 2.47 × 103 KDa was purified with the Sephadex G-150 column. The monosaccharide composition analysis showed that PDP-1 consisted of Man, Glc and Gal in a ratio of 1.678:1.784:1, respectively. Besides, the methylation analysis indicated that PDP-1 was composed of six sugar alcohol derivatives, which were →4，6)-D-Galp-(1→, →4)-D-Galp-(1→, →4)-D -Manp-(1→, →4)-D-Glcp-(1→, →6)-D -Glcp-(1→ and D-Glcp-(1 → . Otherwise, the microscopic conformation of PDP-1 was flat, dense and porous. In addition, the PDP-1 had a strong scavenging ability for DPPH free radicals, Hydroxyl free radicals and ABTS free radicals. At the same time, PDP-1 could effectively decrease the peroxidation process of kidney and heart in mice with acute alcoholic liver injury, improve its antioxidant capacity, and protect the organ injury caused by alcohol to a certain extent. Therefore, the results of this manuscript showed that Piperis Dahongpao polysaccharides have antioxidant potential, which lays a theoretical foundation for the research of Piperis Dahongpa polysaccharides in medicine.