Alcohol-treated Group Research Articles

Targeted Inhibition of Upregulated Sodium-Calcium Exchanger in Rat Inferior Colliculus Suppresses Alcohol Withdrawal Seizures.

The inferior colliculus (IC) is critical in initiating acoustically evoked alcohol withdrawal-induced seizures (AWSs). Recently, we reported that systemic inhibition of Ca2+ entry via the reverse mode activity of the Na+/Ca2+ exchanger (NCXrev) suppressed AWSs, suggesting remodeling of NCX expression and function, at least in the IC, the site of AWS initiation. Here, we probe putative changes in protein expression in the IC of NCX isoforms, including NCX type 1 (NCX1), 2 (NCX2), and 3 (NCX3). We also evaluated the efficacy of targeted inhibition of NCX1rev and NCX3rev activity in the IC on the occurrence and severity of AWSs using SN-6 and KB-R943, respectively. We used our well-characterized alcohol intoxication/withdrawal model associated with enhanced AWS susceptibility. IC tissues from the alcohol-treated group were collected 3h (before the onset of AWS susceptibility), 24h (when AWS susceptibility is maximal), and 48h (when AWS susceptibility is resolved) following alcohol withdrawal; in comparison, IC tissues from the control-treated group were collected at 24h after the last gavage. Analysis shows that NCX1 protein levels were markedly higher 3 and 24h following alcohol withdrawal. However, NCX3 protein levels were only higher 3h following alcohol withdrawal. The analysis also reveals that bilateral microinjections of SN-6 (but not KB-R7943) within the IC markedly suppressed the occurrence and severity of AWSs. Together, these findings indicate that NCX1 is a novel molecular target that may play an essential role in the pathogenesis and pathophysiology of AWSs.

The investigation of the effects of postnatal alcohol exposure on molecular content and antioxidant capacity of mice liver tissue

One of the most common causes of fetal alcohol spectrum disease (FASD) characterized with neurodevelopmental disorder and growth retardation, is the postnatal alcohol consumption. Since studies in literature are mainly focused on alcohol-induced effects on brain tissues, the molecular effects of postnatal alcohol consumption on fetal liver are not clarified yet. The aim of this study is to determine the postnatal alcohol consumption-induced structural and compositional changes on liver tissue and the antioxidant capacity of liver. Newborn mice were divided into 3 groups as control group without any treatment, alcohol group treated with 3.0 g/kg of ethanol in 0.02 ml/g of artificially enriched milk between Postnatal Days (PD) 3–20 and intragastric intubation control group which was intragastrically intubated in the same method as the alcohol group but without ethanol/milk. These postnatal days in mice refers prenatal period (third trimester) of gestation in human. The biomolecular changes were determined by ATR-FTIR spectral analysis of the samples, besides the biochemical measurement of total protein content and antioxidant capacity of liver tissue. The result of the current study shows that while there was a slight increase in total lipid content, significant decrease in unsaturated lipid and total protein contents and total antioxidant capacity of liver were observed in alcohol-treated group. Thus, it is concluded that postnatal alcohol treatment causes significant changes in tissue proteins and lipids by inducing lipid peroxidation and changes in protein conformations of the liver tissue. In addition to that alcohol consumption also reduce the antioxidant capacity of liver tissue.

The Possible Role of Naringenin in the Prevention of Alcohol-Induced Neurochemical and Neurobehavioral Deficits

Chronic alcohol consumption is associated with progressive/irreversible neurodegeneration. However, there is not a clear understanding of its discrete pathophysiology or therapeutic intervention. The present study aimed to investigate the protective effect of the natural citrus flavonoid, naringenin (NAG), against alcohol-induced neurodegeneration in the brain cerebral cortex. Thirty-two male albino rats were randomly divided into four equal groups (eight rats each): control group (I); NAG-treated group (II); alcohol-intoxicated group (III) and alcohol + NAG co-treated group (IV). Brain nuclear factor erythroid 2-related factor 2 and receptor-interacting protein kinase 3 expression were assessed by real-time polymerase chain reaction. NAD(P)H quinone oxidoreductase 1 activity and malondialdehyde, reduced glutathione, mixed lineage kinase-like protein, phosphorylated glycogen synthase kinase 3 beta, and ciliary neurotrophic factor levels were all measured biochemically. B-cell lymphoma 2 expression was assessed by immunohistochemistry. A histopathological examination and neurobehavioral tests were performed. The alcohol-treated group showed a significant increase in oxidative stress and necroptosis biomarkers with a significant reduction in neuroprotective proteins. NAG co-administration effectively ameliorated cognitive dysfunction with an apparent neuroprotective effect by targeting various signaling pathways, including nuclear factor erythroid 2-related factor/NAD(P)H quinone oxidoreductase 1, anti-oxidant capacity, attenuated necroptosis, and upregulated neuroprotective ciliary neurotrophic factor. The study findings suggest NAG as a possible management strategy for alcohol-induced neurodegeneration.

Flos Carthami Exerts Hepatoprotective Action in a Rat Model of Alcoholic Liver Injury via Modulating the Metabolomics Profile.

This study was intended to identify the shifts in the metabolomics profile of the hepatic tissue damaged by alcohol consumption and verify the potential restorative action of flos carthami (the flowers of Carthamus tinctorius, FC) in the protection of alcohol-induced injury by attenuating the level of identified metabolites. Rats were treated with FC and subsequently subjected to alcohol administration. The serum samples were subjected to liquid chromatography-mass spectrometry (LC-MS)-based metabolomics followed by statistical and bioinformatics analyses. The clustering of the samples showed an obvious separation in the principal component analysis (PCA) plot, and the scores plot of the orthogonal partial least squares-discriminant analysis (OPLS-DA) model allowed the distinction among the three groups. Among the 3211 total metabolites, 1088 features were significantly different between the control and alcohol-treated groups, while 367 metabolites were identified as differential metabolites between the alcohol- and FC-treated rat groups. Time series clustering approach indicated that 910 metabolites in profile 6 were upregulated by alcohol but subsequently reversed by FC treatment; among them, the top 10 metabolites based on the variable importance in projection (VIP) scores were 1-methyladenine, phenylglyoxylic acid, N-acetylvaline, mexiletine, L-fucose, propylthiouracil, dopamine 4-sulfate, isoleucylproline, (R)-salsolinol, and monomethyl phthalate. The Pearson correlation analysis and network construction revealed 96 hub metabolites that were upregulated in the alcohol liver injury model group but were downregulated by FC. This study confirmed the hepatoprotective effects of FC against alcohol-induced liver injury and the related changes in the metabolic profiles, which will contribute to the understanding and the treatment of alcohol-induced acute liver injury.

Magnesium isoglycyrrhizinate attenuates acute alcohol-induced hepatic steatosis in a zebrafish model by regulating lipid metabolism and ER stress

BackgroundAlcoholism is a well-known risk factor for liver injury and is one of the major causes of hepatic steatosis worldwide. Although many drugs have been reported to have protective effects against acute alcohol-induced hepatotoxicity, there is limited available treatment for alcoholic liver disease (ALD), indicating an urgent need for effective therapeutic options. Herein, we first reported the protective effects of magnesium isoglycyrrhizinate (MgIG) on acute alcohol-induced hepatic steatosis and its related mechanisms in a zebrafish model.MethodsAlcohol was administered directly to embryo medium at 5 days post-fertilization (dpf) for up to 32 h. MgIG was given to the larvae 2 h before the administration of alcohol and then cotreated with alcohol starting at 5 dpf. Oil red O staining was used to determine the incidence of steatosis, and pathological features of the liver were assessed by hematoxylin–eosin staining. Biological indexes, total cholesterol (TC) and triacylglycerol (TG) were detected in the livers of zebrafish larvae. Morphological changes in the livers of zebrafish larvae were observed using liver-specific EGFP transgenic zebrafish (Tg(lfabp10a:eGFP)). The expression levels of critical molecules related to endoplasmic reticulum (ER) stress and lipid metabolism were detected by qRT–PCR, whole-mount in situ hybridization and western blotting.ResultsAlcohol-treated larvae developed hepatomegaly and steatosis after 32 h of exposure. We found that MgIG improved hepatomegaly and reduced the incidence of steatosis in a dose-dependent manner by oil red O staining and diminished deposits of alcohol-induced fat droplets by histologic analysis. Moreover, MgIG significantly decreased the levels of TC and TG in the livers of zebrafish larvae. Furthermore, the expression levels of critical genes involved in ER stress (atf6, irela, bip, chop) and the key enzymes regulating lipid metabolism (acc1, fasn, hmgcs1 and hmgcra) were significantly higher in the alcohol-treated group than in the control group. However, in the MgIG plus alcohol-treated group, the expression of these genes was markedly decreased compared with that in the alcohol-treated group. Whole-mount in situ hybridization and western blotting also showed that MgIG had an effect on the expression levels of critical genes and proteins involved in lipid metabolism and ER stress. Our results revealed that MgIG could markedly regulate these genes and protect the liver from ER stress and lipid metabolism disorders.ConclusionsOur study is the first to demonstrate that MgIG could protect the liver from acute alcohol stimulation by ameliorating the disorder of lipid metabolism and regulating ER stress in zebrafish larvae.

Neuroprotective effects of feeding Centella asiatica (L) Urb. – Study of hippocampal neurons in pups born to alcohol-fed female Wistar rats

Objectives: To evaluate the neuroprotective function of C. asiatica on the offsprings in maternal alcohol abuse. Centella Asiatica (C. asiatica) has been known to Indian traditional medicine Ayurveda as an effective brain tonic. Alcohol is an abused substance and poses a health risk to all in society, including pregnant women. We force-fed alcohol to pregnant rats and studied its effect on rat pups' hippocampus, which were fed with C. asiatica. The results were also correlated to the cognitive performance of the animals. Methods: Adult female rats, confirmed of pregnancy, were fed with 30% (w/v) alcohol at a dosage of 20g/kg body weight, daily oral gavage. The pups were divided into seven groups (n=6 each) as control and experimental/treated. Results: Hippocampus was isolated, and the slices were stained, and the cell count was done by applying appropriate techniques. The pup quality, cognitive parameters showed differences in alcohol-treated groups. The cell count was performed and compared among the groups. A significant increase in the cell count and the hippocampal neuron population's size was observed in the rats fed with C. asiatica extract. The pup quality was also better. Their cognitive performance was significantly better. Conclusion: This study revealed the adverse effects of fetal alcohol exposure, which reversed after treatment with C. asiatica. This study confirms the role of C. asiatica as an effective neuroprotective agent, and it could be useful to treat the patients suffering from the effects of exposure to alcohol in fetal life and early childhood.

Tramadol aggravates cardiovascular toxicity in a rat model of alcoholism: Involvement of intermediate microfilament proteins and immune-expressed osteopontin.

Tramadol and alcohol are among commonly abused drugs. Although there are potential dangers reported upon their mixing, there are no previous reports describing this mixture's effects on the cardiovascular system (CVS). The aim was to study the effects of mixed alcohol and tramadol on the CVS of adult male rats. Fifty rats were divided into four groups: control, tramadol-treated group, alcohol-treated, and coadministration groups. Tramadol caused a significant increases in creatine kinase-MB, troponin I, malondialdehyde, protein carbonyl, 8-hydroxy-2'-deoxyguanosine, and a significant decrease in total antioxidant capacitywith histological alterations in sections of the heart and aorta and a significant increase in the area% of collagen fibers while there was a nonsignificant difference in body weight, heart weight, heart weight/body weight ratio, lipid profile, tissue tumor necrosis factor-αand interferon-γ, intermediate microfilament proteins (IFPs) {desmin, vimentin, connexin43} gene expression, mean area% of elastic fibers in aortic tissue and osteopontin expression in cardiac and aortic tissue. Alcohol treatment caused a significant change in all the measured parameters and more damage in histological sections. The changes were highest in the coadministration group. There was a strong positive correlation between the area% of collagen fibers and vimentin gene expression, and the area% of osteopontin expression was positively correlated to connexin43 in cardiac and vascular tissue. Tramadol causes CVS injury mainly through oxidative stresses, while the alcohol effect is multifactorial; mixing both aggravates CVS injury. The study also highlights the role of IFPs and osteopontin-expression in inducing injury.

Fatty acid ethyl esters in meconium: A biomarker of fetal alcohol exposure and effect.

To determine if meconium fatty acid ethyl esters (FAEE) in rat pups is a good biomarker of prenatal exposure and effect to alcohol, three groups of pregnant rats were studied: one control (pair fed) and two treatment groups given 25% alcohol at 2.2 or 5.5 g-1 kg-1 d-1. The pups were delivered on day 20 and, for each dam, were separated into a male and female group. The body, brain, intestines, and placenta of the pups were obtained, weighed, and stored at -20°C. The pups' intestines (as surrogate of meconium) from each group were pooled, and meconium was analyzed by gas chromatography/mass spectroscopy for FAEE. The meconium showed the following FAEE: ethyl palmitate, ethyl stearate, and ethyl linolenate and were only found in the alcohol-treated group and with high specificity but low sensitivity. Mean body weight of the pups was lower in the treatment groups compared to the control groups. Ethyl palmitate concentration correlated negatively to the pups' mean body and brain weights. Therefore, ethyl palmitate, stearate, and linolenate, in meconium of rat pups prenatally exposed to alcohol, are useful biomarkers of prenatal alcohol exposure, with ethyl palmitate a good biomarker of adverse effect on the pups' body and brain weight.

Role of alcohol in the induction of hepatic injury by chronic consumption of medicated wine

Kinmen Benefit Life medicated wine (KBLMW), a medicated wine with unified formulas proclaimed by the Committee on Chinese Medicine and Pharmacy (Department of Health, Executive Yuan, Taiwan), was made of 17 kinds of Chinese medicinal materials soaked in 25% alcohol. KBLMW has been widely used as conventional or complementary medicines for health regimen. In the present study, Wistar rats were administered once daily via gastric tube with KBLMW, de-alcoholic KBLMW (0% alcohol/vol) or 25% alcohol at 2.08 mL/kg/day for 12 consecutive weeks, to clarify the role of alcohol in the induction of hepatic disorders by chronic consumption of KBLMW at the recommended intake amount. At the end of this treatment, the liver fibrosis in rats receiving 25% alcohol was found, featuring increase in serum levels of alanine transaminase and aspartate aminotransferase, as well as hepatic hydroxyproline contents. Comparing with the normal group, values of these serum indexes in KBLMW-fed rats elevated moderately but lower than those of 25% alcohol-fed rats. Also, the stage of liver fibrosis in KBLMW-treated rats was less advanced than that in 25% alcohol-treated group. In addition, the liver function parameters in rats receiving de-alcoholic KBLMW were close to those of normal group and liver fibrosis was not observed. The results suggest that alcohol is related to the induction of hepatic injury by chronic consumption of medicated wine even at the recommended daily intake amount. This finding can be used as the safety reference guide for clinical medicated wine drinking.

Gene expression profiling in the hippocampus of adolescent rats after chronic alcohol administration.

In South Korea, the average age of onset of alcohol drinking is 13.3years and half of adolescents drink alcohol more than once a month; 8.45% of the Korean adolescent population become future high-risk alcohol drinkers. Chronic alcohol abuse causes physical and psychiatric health problems such as alcohol addiction, liver disease, stroke and cognitive impairments. This study aimed to investigate the effect of alcohol on gene expression and their function in the hippocampus of adolescent rats. After chronic alcohol administration in male (control, n=6; alcohol, n=6) Sprague-Dawley rats for 6weeks, we analysed up- or down-regulated genes using RNA-sequencing technology. We found 83 genes more than 1.5-fold up- or down-regulated in the alcohol-treated group. Among them, genes (Dnai1, Cfap206 and Dnah1) associated with cilium movement were up-regulated in the alcohol-treated group. Mlf1, related to cell cycle arrest, was also up-regulated in the alcohol-treated group. On the other hand, genes (Smad3 and Plk5) involved in negative regulation of cell proliferation were down-regulated in the hippocampus by chronic alcohol administration. In addition, expression levels of genes associated with oxidative stress (Krt8 and Car3) and migration (Vim) were changed by chronic alcohol administration. These results pave a path for a better understanding of the neuromolecular mechanisms mediated by chronic alcohol exposure in the hippocampus of adolescents and negative pathology due to chronic alcohol abuse.

Protective effect of Carthamus tinctorius L. seed on oxidative stress and cognitive impairment induced by chronic alcohol consumption in mice.

Chronic alcohol consumption induces damage to the brain that can cause various forms of dementia. An abundance of acetaldehyde is produced by excessive alcohol consumption and accumulates in the body to induce oxidative stress, apoptosis, and inflammation in neuronal cells, which results in learning and cognitive decline. In the present study, C57BL/N mice were orally administered alcohol (16%) and Carthamus tinctorius L. seed (CTS) (100 and 200mg/kg/day). Behavioral experiments showed that memory and cognitive abilities were significantly higher in the CTS groups than the alcohol-treated control group in the T-maze test, novel object recognition test, and Morris water maze test. In addition, CTS inhibited alcohol-induced lipid peroxidation and nitric oxide production in the brain, kidney, and liver. Moreover, alcohol increased acetylcholinesterase activity in the brain, but this was significantly decreased by the administration of CTS. Therefore, CTS may play role in the prevention of alcohol-related dementia.

Expression Profiling of Circular RNAs and Micrornas in Heart Tissue of Mice with Alcoholic Cardiomyopathy

Background/Aims: Chronic heavy alcohol consumption may result in alcoholic cardiomyopathy. This study was designed to screen differentially expressed microRNAs and circular RNAs in heart tissue of mice with alcoholic cardiomyopathy to reveal the underlying molecular mechanism. Methods: Having established a murine alcoholic cardiomyopathy model, we screened differentially expressed microRNAs and circular RNAs in three heart samples from the alcohol-treated and control groups by high-throughput microarray analysis. We analyzed the function and biological signaling pathways of differentially expressed non-coding RNAs closely related to alcoholic cardiomyopathy using bioinformatics software to identify some mRNAs and their biological signaling pathways closely related to alcoholic cardiomyopathy. Results: Nineteen microRNAs and 265 circular RNAs were differentially expressed in the alcohol-treated group compared with the control group. After analyzing gene function and signaling pathways by bioinformatics software, we found that the differentially expressed mRNAs were associated with carbohydrate metabolism. Conclusions: Chronic alcohol consumption can change the non-coding RNA profile of heart tissue, which is closely related to the pathological mechanisms of alcoholic cardiomyopathy.

Standardized Passiflora incarnata L. Extract Reverts the Analgesia Induced by Alcohol Withdrawal in Rats.

Passiflora incarnata L. (Passifloraceae) has been traditionally used for treatment of anxiety, insomnia, drug addiction, mild infections, and pain. The aim of this study was to investigate the effect of a commercial extract of P. incarnata in the analgesia induced by alcohol withdrawal syndrome in rats. In addition, brain-derived neurotrophic factor and interleukin-10 levels were evaluated in prefrontal cortex, brainstem, and hippocampus. Male adult rats received by oral gavage: (1: water group) water for 19days, 1day interval and water (8days); (2: P. incarnata group) water for 19days, 1day interval and P. incarnata 200mg/kg (8days); (3: alcohol withdrawal group) alcohol for 19days, 1day interval and water (8days); and (4: P. incarnata in alcohol withdrawal) alcohol for 19days, 1day interval and P. incarnata 200mg/kg (8days). The tail-flick and hot plate tests were used as nociceptive response measures. Confirming previous study of our group, it was showed that alcohol-treated groups presented an increase in the nociceptive thresholds after alcohol withdrawal, which was reverted by P. incarnata, measured by the hot plate test. Besides, alcohol treatment increased brain-derived neurotrophic factor and interleukin-10 levels in prefrontal cortex, which was not reverted by P. incarnata. Considering these results, the P. incarnata treatment might be a potential therapy in the alcohol withdrawal syndrome. Copyright © 2017 John Wiley & Sons, Ltd.

Nerve Growth Factor Protects Against Alcohol-Induced Neurotoxicity in PC12 Cells via PI3K/Akt/mTOR Pathway.

To study whether autophagy participates in the neuroprotective effect of nerve growth factor (NGF) on neurons treated with alcohol. The autophagy-related markers were used to explore the role of autophagy in PC12 cells exposed to alcohol or pre-incubated with NGF before initiating the treatment with alcohol (100 mM; 6 h). PC12 cells were pre-incubated with 3-methyladenine (3-MA) (10 mM; 1 h) or rapamycin (100 nM; 1 h) before co-incubated with alcohol (100 mM; 6 h) in order to investigate the relationship between apoptosis and autophagy. PC12 cells were pre-incubated with LY294002 (50 μM; 30 min) before co-incubated with NGF and alcohol in order to analyze the protein expression of PI3K/Akt/mTOR pathway via western blotting. By methylthiazoltetrazolium, western blotting and flow cytometry assays, we found that cell viability decreased in a dose- and time-dependent manner after treatment with alcohol in PC12 cells. As cells were exposed to alcohol, the levels of LC3-II proteins became elevated, likewise, pre-treatment with 3-methyladenine (3-MA, an autophagic inhibitor) or rapamycin (an autophagic inducer) resulted in an increased or decreased percentage of apoptosis in contrast to other alcohol-treated groups, respectively. NGF markedly increased LC3-II production after treatment with alcohol in a dose-dependent manner. Moreover, NGF remarkably attenuated the phosphorylation effect of alcohol exposure on PI3K/Akt/mTOR pathway, which was suppressed by LY294002 (Akt inhibitor). NGF protects against alcohol-induced neurotoxicity via PI3K/Akt/mTOR pathway. In this study, we chose the PC12 cell line as a neuronal model, and our results demonstrate that nerve growth factor can induce autophagy with the neuroprotective effect and regulatory mechanisms of alcohol-induced autophagy in PC12 cells.

Establishment of an alcoholic fatty liver disease model in mice

ABSTRACTBackground: Alcoholic fatty liver disease (AFLD) defines an important stage in the progression of alcoholic liver disease (ALD), which is a major cause of morbidity and mortality worldwide. Objective: To establish a mouse model of AFLD. Methods: Male C57BL/6 mice were divided into the following two groups: (i) a control group, which was allowed free access to food and water and (ii) an alcohol-treated group, which was administered a 15% (v/v) alcohol solution instead of water. After 8–9 months of treatment, serum biochemical indexes, histopathological changes, liver triglyceride content, iron storage, and ferritin light chain protein expression were measured using an automatic biochemical analyzer, hematoxylin–eosin (HE) staining, a commercially available kit, Prussian blue staining, and Western blot analysis, respectively. Results: Compared with the control group, the alcohol-treated group displayed increased levels of serum LDH, ALT, and AST, decreased levels of ALB, and no significant change in levels of TP. Additionally, increased levels of serum TG, T-CHO, and LDL and decreased levels of serum GLU and HDL were observed in the alcohol-treated mice. HE staining showed that lipid vacuolization occurred in the livers of alcohol-treated mice. The alcohol-treated mice also exhibited increased liver triglyceride content. Moreover, Prussian blue staining and Western blot analysis demonstrated that chronic alcohol administration caused iron overloading of the liver. Conclusions: Chronic administration of 15% (v/v) alcohol in the drinking water over 8–9 months caused AFLD in mice. Our results establish an AFLD model that represents a promising tool for the future study of the progression of ALD.

Abstract P116: Exercise Ameliorated Cognitive Impairment Through ER Stress Mitigation in Alcohol Treated Exercise Ameliorated Cognitive Impairment Through Er Stress Mitigation in Alcohol Treated C57bl/6 Male Mice

Alcohol consumption is a potent inducer of oxidative stress (OS). Oxidative stress cause disturbance of endoplasmic reticulum (ER) homeostasis, that triggers ER stress (ERS), cause neuronal damage in the brain. Our Previous data indicate that Alcohol consumption induces mitochondrial dysfunction and free radical production in mouse cerebral cortex. Exercise has been recommended by clinicians as a secondary protective therapy; however, its effect on brain functions through ER stress has not been fully explored. Therefore, we hypothesized that exercise improves Alcohol-induced neurodegeneration and decline in cognitive function through ER stress mitigation. To test this hypothesis, we selected 10-12 weeks old male wild-type mice (C57BL/6, WT), grouped as follows: 1) WT, 2) WT+ Alcohol, 3) WT+ Exercise, 4) WT+ Alcohol + Exercise. Mice were given an intraperitoneal injection of Alcohol (1.5g/kg BW) or saline solution every day for 8 weeks. The mice were exercised for 8 weeks on a treadmill with a controlled speed of 7 meters/min for the first week, the speed of 10 meters/min for the second week and 11 meters/min in the following weeks and a total of 330 meters every day. After each 110 meters mice were given rest of 10 minutes. Cognitive and behavior alterations were assessed by novel object recognition, Passive avoidance, and Y-maze tests. Our result showed there is a significantly impaired cognitive and behavior functions (600.00 ± 0.00 vs 480 ± 20.00, P<0.05) in Alcohol-treated group compared to WT control mice. However exercised significantly improved (0.37 ± 0.05 vs 0.63 ± 0.04 P<0.01) these functions as compared to Alcohol-treated group. Also, we observed an elevated blood pressure in the Alcohol-treated group (123.50 ± 1.17) and exercise brought that to the normal level (108.98 ± 4.47, P<0.01). In addition, the effect of exercise on neuronal survival in the Alcohol-treated mouse brain was confirmed by a decrease in by fluoro-jade C reactivity. Taken together, our results indicate a myriad of beneficiary effects of exercise over ER mitigation in Alcohol-treated mice. Furthermore, our findings suggest exercise alleviates neurodegeneration and cognitive dysfunction and thereby improving total brain function. This work was supported by NIH grant HL107640-NT

Effects of shilajit on the bone tissue of alcohol administered rats

Purpose: The purpose of the current study was to examine the effect of Shilajit; a herbomineral, supplementation on the mechanical strength of alcohol treated rat bone. Methods: Experimental animals each were assigned to six groups: group A(control): control rats were given water orally for a period of ten weeks; group B (treated): Animals were given processed shilajit (PS; 100mg/kg/day); group C (treated): Animals were given processed shilajit (PS; 200mg/kg/day); group D: animals were given 30% alcohol; group E: animals were given 30% alcohol and shilajit (100mg/kg/day) orally; group F: animals were given 30% alcohol and shilajit (200mg/kg/day) orally for ten weeks. Bone tissue mechanical strength along with bone weight, liver antioxidative enzymes and alkaline phosphatase (ALP) were assessed for all the treatment groups. Results: Mechanical strength of the bone tissue (both femur as well as tibia) was found to be significantly enhanced upon shilajit supplementation to alcohol treated group. Also, the activities of anti oxidant enzymes and alkaline phosphatase in the liver of alcohol administered groups were restored upon shilajit administration. Conclusion: These findings suggest that shilajit is very efficacious and competent in the maintenance of bone health.

All-trans retinoic acid improves iodine uptake of thyroid cancer cells via repressing transcriptional activity of β-catenin

To determine whether all-trans retinoic acid (ATRA) could improve iodine uptake via repressing transcriptional activity of β-catenin in thyroid cancer cells. Three kinds of treatment models were firstly established with alcohol, ATRA, and transfection of β-catenin shRNA in undifferentiated human thyroid cancer cell line-SW1736.Then the expressions of sodium iodide symporter (NIS), β-catenin and its regulating factors, epithelial-mensechymal transition (EMT)-phenotype, invasion and metastasis associated proteins were further measured in above three cell models.After that, the influence of ATRA on the functional expression of NIS, iodine uptake potency, tumor growth curve and treatment effect inducing by radioactive iodine was comparatively analyzed in vitro and in vivo trials. After treated with ATRA, transcriptional activity of β-catenin decreased by downregulating phosphorylation of β-catenin Ser45, Y654 and GSK-3β Ser9. Additionally, ATRA effectively upregulated the protein level of NIS, and reversed EMT phenotype in alcohol treated cells, with absence in epithelial expression of E-cadherin and cytokeratin 18, as well as abnormal expression of Vimentin, urinary plasminogen activator (uPA), uPAR and Fibronectin.Compared with alcohol-treated group, both in vitro proliferation and invasion potential of ATRA treated cells markedly decreased (all P<0.05), and iodine uptake in vitro increased about 3.5-folds (P=0.007). In ATRA-treated animal model, tumor growth potential and tumor mass were significantly inhibited by radio-iodine ((131)I) treatment (all P<0.05). ATRA can increase functional expression of NIS via downregulating transcriptional activity of β-catenin and promote isotope sensitivity to radio-iodine in human undifferentiated thyroid cancer.

Purple potato (Solanum tuberosum L.) anthocyanins attenuate alcohol-induced hepatic injury by enhancing antioxidant defense.

Alcoholic liver disease (ALD) is a serious and challenging health issue. In the past decade, natural components possessing hepatoprotective properties have gained more attention for ALD intervention. In this study, the phytochemical components of anthocyanins from purple potato were assessed using UPLC-MS/MS, and the hepatoprotective effects of purple potato anthocyanins (PPAs) were investigated in the ALD mouse model. Serum and liver biochemical parameters were determined, along with histopathological changes in liver tissue. In addition, the major contributors to alcohol-induced oxidative stress were assessed. The results indicated that the levels of aspartate transaminase and alanine transaminase were lower in the serum of the PPA-treated group than the alcohol-treated group. PPAs significantly inhibited the reduction of total cholesterol and triglycerides. Higher levels of superoxide dismutase and reduced glutathione enzymes as well as a reduction in the formation of malondialdehyde occurred in mice fed with PPAs. In addition, PPAs protected against increased alcohol-induced levels and activity of cytochrome P450 2E1 (CYP2E1), which demonstrates the effects of PPAs against alcohol-induced oxidative stress and liver injury. This study suggests that PPAs could be an effective therapeutic agent in alcohol-induced liver injuries by inhibiting CYP2E1 expression and thereby strengthening antioxidant defenses.

Changes of the Cytoplasmic Proteome in Response to Alcoholic Hepatotoxicity in Rats.

Proteomic analyses have already been used in a number of hepatological studies and provide important information. However, few reports have focused on changes in the cytoplasmic proteome. The present study therefore aimed to evaluate changes in cytoplasmic proteome of rats in response to alcoholic hepatotoxicity. Rats were fed a Liber-DeCarli liquid diet containing ethanol for four weeks. Cytoplasmic proteins except mitochondrial proteins from the livers of these animals were investigated using two-dimensional gel electrophoresis and mass spectrometry. Alcohol induced a decrease in body weight gain and an increase in alanine transaminase (ALT), cholesterol, and phospholipid levels. Histopathological observations revealed hepatic damage characterized by necrosis and fatty change in alcohol-treated group at week 2, which continues until week 4. Our proteomic analysis revealed that 25 proteins were differentially expressed in the ethanol-fed group. Of these, 12 cytoplasmic proteins are being reported for the first time. Taken together, our results provide further insights into the disease mechanism and therapeutic information of alcoholic liver disease.