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Sample records for alcohol induced region-dependent

  1. Alcohol-Induced Blackout

    Dai Jin Kim

    2009-11-01

    Full Text Available For a long time, alcohol was thought to exert a general depressant effect on the central nervous system (CNS. However, currently the consensus is that specific regions of the brain are selectively vulnerable to the acute effects of alcohol. An alcohol-induced blackout is the classic example; the subject is temporarily unable to form new long-term memories while relatively maintaining other skills such as talking or even driving. A recent study showed that alcohol can cause retrograde memory impairment, that is, blackouts due to retrieval impairments as well as those due to deficits in encoding. Alcoholic blackouts may be complete (en bloc or partial (fragmentary depending on severity of memory impairment. In fragmentary blackouts, cueing often aids recall. Memory impairment during acute intoxication involves dysfunction of episodic memory, a type of memory encoded with spatial and social context. Recent studies have shown that there are multiple memory systems supported by discrete brain regions, and the acute effects of alcohol on learning and memory may result from alteration of the hippocampus and related structures on a cellular level. A rapid increase in blood alcohol concentration (BAC is most consistently associated with the likelihood of a blackout. However, not all subjects experience blackouts, implying that genetic factors play a role in determining CNS vulnerability to the effects of alcohol. This factor may predispose an individual to alcoholism, as altered memory function during intoxication may affect an individual‟s alcohol expectancy; one may perceive positive aspects of intoxication while unintentionally ignoring the negative aspects. Extensive research on memory and learning as well as findings related to the acute effects of alcohol on the brain may elucidate the mechanisms and impact associated with the alcohol- induced blackout.

  2. Alcohol induced osteopenia

    Keck, E.; Bremer, G.; Franck, H.

    1986-01-01

    There is a clear evidence of a propensity to fractures and the development of osteomalacia, osteoporosis, and mixed forms in chronic alcoholics. Osteomalacia is associated with impaired vitamin D status, probably due to enzyme induction in liver and kidney and development of a secondary intestinal hyperparathyroidism. The development of osteoporosis is multifactorial, but seems to arise mainly through reduction in bone formation and reduced dietary protein and calcium intake. Low testosterone levels may also contribute to osteoporosis. (orig.) [de

  3. Alcohol induced osteopenia

    Keck, E.; Bremer, G.; Franck, H.

    1986-12-01

    There is a clear evidence of a propensity to fractures and the development of osteomalacia, osteoporosis, and mixed forms in chronic alcoholics. Osteomalacia is associated with impaired vitamin D status, probably due to enzyme induction in liver and kidney and development of a secondary intestinal hyperparathyroidism. The development of osteoporosis is multifactorial, but seems to arise mainly through reduction in bone formation and reduced dietary protein and calcium intake. Low testosterone levels may also contribute to osteoporosis.

  4. Acute alcohol-induced liver injury

    Gavin Edward Arteel

    2012-06-01

    Full Text Available Alcohol consumption is customary in most cultures and alcohol abuse is common worldwide. For example, more than 50% of Americans consume alcohol, with an estimated 23.1% of Americans participating in heavy and/or binge drinking at least once a month. A safe and effective therapy for alcoholic liver disease (ALD in humans is still elusive, despite significant advances in our understanding of how the disease is initiated and progresses. It is now clear that acute alcohol binges not only can be acutely toxic to the liver, but also can contribute to the chronicity of ALD. Potential mechanisms by which acute alcohol causes damage include steatosis, dysregulated immunity and inflammation and altered gut permeability. Recent interest in modeling acute alcohol exposure has yielded new insights into potential mechanisms of acute injury, that also may well be relevant for chronic ALD. Recent work by this group on the role of PAI-1 and fibrin metabolism in mediating acute alcohol-induced liver damage serve as an example of possible new targets that may be useful for alcohol abuse, be it acute or chronic.

  5. Alcohol-induced sexual behavior on campus.

    Meilman, P W

    1993-07-01

    This study investigated the prevalence of alcohol-related sexual activity on campus. Since coming to college, 35% of the students had engaged in some form of sexual activity that was influenced by drinking. Because they had been drinking, 18% had engaged in sexual intercourse, and 15% had abandoned safe-sex techniques. For the categories any form of sexual activity and abandonment of safe-sex techniques, a significantly greater percentage of women were affected by alcohol use, but this was not true for sexual intercourse. The survey showed no significant differences between undergraduate and graduate students. All three variables showed a relationship with heavier alcohol use and with binge drinking. Academic excellence was negatively correlated with alcohol-induced sexual intercourse.

  6. Gut microbiota modulates alcohol withdrawal-induced anxiety in mice.

    Xiao, Hui-Wen; Ge, Chang; Feng, Guo-Xing; Li, Yuan; Luo, Dan; Dong, Jia-Li; Li, Hang; Wang, Haichao; Cui, Ming; Fan, Sai-Jun

    2018-05-01

    Excessive alcohol consumption remains a major public health problem that affects millions of people worldwide. Accumulative experimental evidence has suggested an important involvement of gut microbiota in the modulation of host's immunological and neurological functions. However, it is previously unknown whether enteric microbiota is implicated in the formation of alcohol withdrawal-induced anxiety. Using a murine model of chronic alcoholism and withdrawal, we examined the impact of alcohol consumption on the possible alterations of gut microbiota as well as alcohol withdrawal-induced anxiety and behavior changes. The 16S rRNA sequencing revealed that alcohol consumption did not alter the abundance of bacteria, but markedly changed the composition of gut microbiota. Moreover, the transplantation of enteric microbes from alcohol-fed mice to normal healthy controls remarkably shaped the composition of gut bacteria, and elicited behavioral signs of alcohol withdrawal-induced anxiety. Using quantitative real-time polymerase chain reaction, we further confirmed that the expression of genes implicated in alcohol addiction, BDNF, CRHR1 and OPRM1, was also altered by transplantation of gut microbes from alcohol-exposed donors. Collectively, our findings suggested a possibility that the alterations of gut microbiota composition might contribute to the development of alcohol withdrawal-induced anxiety, and reveal potentially new etiologies for treating alcohol addiction. Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.

  7. Effects of alcohol-induced working memory decline on alcohol consumption and adverse consequences of use.

    Lechner, William V; Day, Anne M; Metrik, Jane; Leventhal, Adam M; Kahler, Christopher W

    2016-01-01

    Alcohol use appears to decrease executive function acutely in a dose-dependent manner, and lower baseline executive function appears to contribute to problematic alcohol use. However, no studies, to our knowledge, have examined the relationship between individual differences in working memory (a subcomponent of executive function) after alcohol consumption and drinking behaviors and consequences. The current study assessed the relationship between drinking behavior, alcohol-related consequences, and alcohol-induced changes in working memory (as assessed by Trail Making Test-B). Participants recruited from the community (n = 41), 57.3 % male, mean age 39.2, took part in a three-session, within-subjects, repeated-measures design. Participants were administered a placebo, 0.4 g/kg, or 0.8 g/kg dose of alcohol. Working memory, past 30-day alcohol consumption, and consequences of alcohol use were measured at baseline; working memory was measured again after each beverage administration. Poorer working memory after alcohol administration (controlling for baseline working memory) was significantly associated with a greater number of drinks consumed per drinking day. Additionally, we observed a significant indirect relationship between the degree of alcohol-induced working memory decline and adverse consequences of alcohol use, which was mediated through greater average drinks per drinking day. It is possible that greater individual susceptibility to alcohol-induced working memory decline may limit one's ability to moderate alcohol consumption as evidenced by greater drinks per drinking day and that this results in more adverse consequences of alcohol use.

  8. Alcohol-induced histone acetylation reveals a gene network involved in alcohol tolerance.

    Alfredo Ghezzi

    Full Text Available Sustained or repeated exposure to sedating drugs, such as alcohol, triggers homeostatic adaptations in the brain that lead to the development of drug tolerance and dependence. These adaptations involve long-term changes in the transcription of drug-responsive genes as well as an epigenetic restructuring of chromosomal regions that is thought to signal and maintain the altered transcriptional state. Alcohol-induced epigenetic changes have been shown to be important in the long-term adaptation that leads to alcohol tolerance and dependence endophenotypes. A major constraint impeding progress is that alcohol produces a surfeit of changes in gene expression, most of which may not make any meaningful contribution to the ethanol response under study. Here we used a novel genomic epigenetic approach to find genes relevant for functional alcohol tolerance by exploiting the commonalities of two chemically distinct alcohols. In Drosophila melanogaster, ethanol and benzyl alcohol induce mutual cross-tolerance, indicating that they share a common mechanism for producing tolerance. We surveyed the genome-wide changes in histone acetylation that occur in response to these drugs. Each drug induces modifications in a large number of genes. The genes that respond similarly to either treatment, however, represent a subgroup enriched for genes important for the common tolerance response. Genes were functionally tested for behavioral tolerance to the sedative effects of ethanol and benzyl alcohol using mutant and inducible RNAi stocks. We identified a network of genes that are essential for the development of tolerance to sedation by alcohol.

  9. The Molecular Circadian Clock and Alcohol-Induced Liver Injury

    Uduak S. Udoh

    2015-10-01

    Full Text Available Emerging evidence from both experimental animal studies and clinical human investigations demonstrates strong connections among circadian processes, alcohol use, and alcohol-induced tissue injury. Components of the circadian clock have been shown to influence the pathophysiological effects of alcohol. Conversely, alcohol may alter the expression of circadian clock genes and the rhythmic behavioral and metabolic processes they regulate. Therefore, we propose that alcohol-mediated disruption in circadian rhythms likely underpins many adverse health effects of alcohol that cut across multiple organ systems. In this review, we provide an overview of the circadian clock mechanism and showcase results from new studies in the alcohol field implicating the circadian clock as a key target of alcohol action and toxicity in the liver. We discuss various molecular events through which alcohol may work to negatively impact circadian clock-mediated processes in the liver, and contribute to tissue pathology. Illuminating the mechanistic connections between the circadian clock and alcohol will be critical to the development of new preventative and pharmacological treatments for alcohol use disorders and alcohol-mediated organ diseases.

  10. Reversibility of alcohol-induced immune depression

    Tønnesen, H; Kaiser, A H; Nielsen, B B

    1992-01-01

    Alcohol abusers have suppressed cellular immune function. The aim of the study was to investigate the time of sobriety required to normalize immune function. Delayed hypersensitivity was investigated during disulfiram controlled abstinence in ten heavy alcoholics and in seven moderate drinkers...... months of abstinence. The results suggest that while 2 weeks of abstinence from alcohol will improve the depressed cellular immunity, 2 months of sobriety is necessary to normalize it....

  11. Evaluation of Moringa oleifera Leaf Extract on Alcohol-induced ...

    induced hepatotoxicity in rats was evaluated. Rats fed alcohol only produced significant increase in the levels of enzyme markers of tissues damage (ALT, AST and ALP), lipid peroxidation (TBARS) and decreased serum vitamin C levels ...

  12. Role of IRAK-M in alcohol induced liver injury.

    Yipeng Wang

    Full Text Available Increasing evidence suggests that innate immunity plays an important role in alcohol-induced liver injury and most studies have focused on positive regulation of innate immunity. The main objective of this study was to investigate the negative regulator of innate immunity, IL-1/Toll-like receptor (TLR signaling pathways and interleukin receptor-associated kinase-M (IRAK-M in alcoholic liver injury. We established an alcohol-induced liver injury model using wild type and IRAK-M deficient B6 mice and investigated the possible mechanisms. We found that in the absence of IRAK-M, liver damage by alcohol was worse with higher alanine transaminase (ALT, more immune cell infiltration and increased numbers of IFNγ producing cells. We also found enhanced phagocytic activity in CD68(+ cells. Moreover, our results revealed altered gut bacteria after alcohol consumption and this was more striking in the absence of IRAK-M. Our study provides evidence that IRAK-M plays an important role in alcohol-induced liver injury and IRAK-M negatively regulates the innate and possibly the adaptive immune response in the liver reacting to acute insult by alcohol. In the absence of IRAK-M, the hosts developed worse liver injury, enhanced gut permeability and altered gut microbiota.

  13. Acute versus chronic alcohol consumption in acetaminophen-induced hepatotoxicity

    Schmidt, L.E.; Dalhoff, K.P.; Poulsen, Henrik E.

    2002-01-01

    . With a time to NAC less than 12 hours, the mortality rate was 0.42% (95% CI, 0.05-2.7). When time to NAC exceeded 12, 24, and 48 hours, the mortality rate increased to 6.1%, 13%, and 19%, respectively. Chronic alcohol abuse was an independent risk factor of mortality (odds ratio [OR], 3.52; 95% CI, 1...... was confirmed as the major risk factor in acetaminophen-induced hepatotoxicity and mortality. Chronic alcohol abuse was an independent risk factor that could be counteracted by concomitant acute alcohol ingestion. We suggest that patients with chronic alcoholism and suspected acetaminophen poisoning due......The aim of this study was to determine by multivariate analysis how alcohol and other factors affect the clinical course and outcome in patients with acetaminophen (paracetamol) poisoning. A total of 645 consecutive patients admitted from 1994 to 2000 with single-dose acetaminophen poisoning were...

  14. Lower risk for alcohol-induced cirrhosis in wine drinkers

    Becker, Ulrik; Grønbaek, Morten; Johansen, Ditte

    2002-01-01

    Although there is a well-known relationship between total alcohol intake and future risk for cirrhosis, other factors such as the type of alcohol consumed are sparsely studied. The aim of this study was to assess the effects of wine compared with other types of alcoholic beverages on risk...... for alcohol-induced cirrhosis. In 3 prospective studies, 30,630 participants from the Copenhagen area were followed-up for a total observation time of 417,325 person-years. Information on weekly intake of beer, wine, and spirits, and sex, age, body mass index, smoking habits, and education was obtained from...... with increasing alcohol intake. Individuals who drank more than 5 drinks per day had a relative risk of 14 to 20 for developing cirrhosis compared with non- or light drinkers. However, compared with individuals who drank no wine (relative risk set at 1.0), individuals drinking 16% to 30% wine of their total...

  15. Cellular and molecular mechanisms of alcohol-induced osteopenia.

    Luo, Zhenhua; Liu, Yao; Liu, Yitong; Chen, Hui; Shi, Songtao; Liu, Yi

    2017-12-01

    Alcoholic beverages are widely consumed, resulting in a staggering economic cost in different social and cultural settings. Types of alcohol consumption vary from light occasional to heavy, binge drinking, and chronic alcohol abuse at all ages. In general, heavy alcohol consumption is widely recognized as a major epidemiological risk factor for chronic diseases and is detrimental to many organs and tissues, including bones. Indeed, recent findings demonstrate that alcohol has a dose-dependent toxic effect in promoting imbalanced bone remodeling. This imbalance eventually results in osteopenia, an established risk factor for osteoporosis. Decreased bone mass and strength are major hallmarks of osteopenia, which is predominantly attributed not only to inhibition of bone synthesis but also to increased bone resorption through direct and indirect pathways. In this review, we present knowledge to elucidate the epidemiology, potential pathogenesis, and major molecular mechanisms and cellular effects that underlie alcoholism-induced bone loss in osteopenia. Novel therapeutic targets for correcting alcohol-induced osteopenia are also reviewed, such as modulation of proinflammatory cytokines and Wnt and mTOR signaling and the application of new drugs.

  16. Gender and Impulsivity: Effects on Cue-Induced Alcohol Craving.

    Yarmush, Devorah E; Manchery, Linda; Luehring-Jones, Peter; Erblich, Joel

    2016-05-01

    Numerous studies have demonstrated that trait impulsivity is linked to increased risk of developing alcohol-use disorders and other substance abuse. Impulsivity has also been shown in some studies to potentiate cue-induced drug cravings. Despite considerable evidence of gender differences in impulsivity and drug craving among individuals suffering from alcohol dependence and other drug use, little research has focused on these processes in healthy young men and women who may be at risk for developing alcohol-use disorders. The objective of this study was to investigate the relationship between impulsivity and cue-induced craving, as well as possible gender differences in these effects among healthy young adults. To that end, female (n = 22) and male (n = 14) social drinkers aged 18 to 25, recruited from an urban university campus, completed the Barratt Impulsiveness Scale and reported their alcohol cravings immediately before and after laboratory exposure to alcohol cues. Findings indicated that exposure to cues elicited increased alcohol cravings, but these effects did not differ by gender. Interestingly, a significant interaction of impulsivity and gender revealed that impulsivity predicted significantly higher cue-induced cravings in women, but not men. Findings underscore the importance of better understanding the interaction of situational factors (e.g., exposure to alcohol cues) and dispositional factors (e.g., impulsivity) as potential contributors to drinking motivation. Future prospective research is needed to identify gender-specific risk factors for the development of problem drinking. Copyright © 2016 by the Research Society on Alcoholism.

  17. Ethyl Alcohol Extract of Hizikia fusiforme Induces Caspase ...

    Ethyl Alcohol Extract of Hizikia fusiforme Induces Caspase-dependent Apoptosis in Human Leukemia U937 Cells by Generation of Reactive Oxygen Species. C-H Kang, S-H Kang, S-H Boo, S-Y Park, D-O Moon, G-Y Kim ...

  18. Ethyl Alcohol Extract of Hizikia fusiforme Induces Caspase ...

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    In this study, the role of the ethyl alcohol extract of H. fusiforme (EAHF) in the induction of apoptosis in ... closely related to the induction of apoptosis via the downregulation of IAP family members such as IAP-. 1, IAP-2 ... induces apoptosis in a variety of cancer cells through ... Total cell extracts were prepared using PRO-.

  19. Caffeine antagonism of alcohol-induced driving impairment.

    Liguori, A; Robinson, J H

    2001-07-01

    The extent to which caffeine antagonizes alcohol-induced impairment of simulated automobile driving at the current lowest legal American limit (0.08% BrAC) was the focus of this study. Fifteen adults swallowed a capsule (0, 200, or 400 mg caffeine) then drank a beverage (0.0 or 0.6 g/kg ethanol) in a within-subject, double-blind, randomized procedure. Forty-five minutes later, participants completed a test battery of subjective effects scales, dynamic posturography, critical flicker fusion (CFF), choice reaction time (CRT), divided attention (Stroop test), and simulated driving. Alcohol alone increased ratings of 'dizzy', 'drug effect', and 'high', slowed CRT and brake latency, and increased body sway. Caffeine alone increased ratings of 'alert' and 'jittery', but did not significantly affect body sway or psychomotor performance. Both caffeine doses comparably counteracted alcohol impairment of brake latency but not CRT or body sway. Brake latency with either alcohol-caffeine combination remained significantly longer than that with placebo. Stroop and CFF performance were unaffected by any drug condition. The results suggest that caffeine may increase alertness and improve reaction time after alcohol use but will not completely counteract alcohol impairment in a driver.

  20. Genetic susceptibility factors for alcohol-induced chronic pancreatitis.

    Aghdassi, Ali A; Weiss, F Ulrich; Mayerle, Julia; Lerch, Markus M; Simon, Peter

    2015-07-01

    Chronic pancreatitis is a progressive inflammatory disease of the pancreas and frequently associated with immoderate alcohol consumption. Since only a small proportion of alcoholics eventually develop chronic pancreatitis genetic susceptibility factors have long been suspected to contribute to the pathogenesis of the disease. Smaller studies in ethnically defined populations have found that not only polymorphism in proteins involved in the metabolism of ethanol, such as Alcohol Dehydrogenase and Aldehyde Dehydrogenase, can confer a risk for developing chronic pancreatitis but also mutations that had previously been reported in association with idiopathic pancreatitis, such as SPINK1 mutations. In a much broader approach employing genome wide search strategies the NAPS study found that polymorphisms in the Trypsin locus (PRSS1 rs10273639), and the Claudin 2 locus (CLDN2-RIPPLY1-MORC4 locus rs7057398 and rs12688220) confer an increased risk of developing alcohol-induced pancreatitis. These results from North America have now been confirmed by a European consortium. In another genome wide approach polymorphisms in the genes encoding Fucosyltransferase 2 (FUT2) non-secretor status and blood group B were not only found in association with higher serum lipase levels in healthy volunteers but also to more than double the risk for developing alcohol-associated chronic pancreatitis. These novel genetic associations will allow to investigate the pathophysiological and biochemical basis of alcohol-induced chronic pancreatitis on a cellular level and in much more detail than previously possible. Copyright © 2015 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  1. Gender differences in alcohol-induced neurotoxicity and brain damage.

    Alfonso-Loeches, Silvia; Pascual, María; Guerri, Consuelo

    2013-09-06

    Considerable evidence has demonstrated that women are more vulnerable than men to the toxic effects of alcohol, although the results as to whether gender differences exist in ethanol-induced brain damage are contradictory. We have reported that ethanol, by activating the neuroimmune system and Toll-like receptors 4 (TLR4), can cause neuroinflammation and brain injury. However, whether there are gender differences in alcohol-induced neuroinflammation and brain injury are currently controversial. Using the brains of TLR4(+/+) and TLR4(-/-) (TLR4-KO) mice, we report that chronic ethanol treatment induces inflammatory mediators (iNOS and COX-2), cytokines (IL-1β, TNF-α), gliosis processes, caspase-3 activation and neuronal loss in the cerebral cortex of both female and male mice. Conversely, the levels of these parameters tend to be higher in female than in male mice. Using an in vivo imaging technique, our results further evidence that ethanol treatment triggers higher GFAP levels and lower MAP-2 levels in female than in male mice, suggesting a greater effect of ethanol-induced astrogliosis and less MAP-2(+) neurons in female than in male mice. Our results further confirm the pivotal role of TLR4 in alcohol-induced neuroinflammation and brain damage since the elimination of TLR4 protects the brain of males and females against the deleterious effects of ethanol. In short, the present findings demonstrate that, during the same period of ethanol treatment, females are more vulnerable than males to the neurotoxic/neuroinflammatory effects of ethanol, thus supporting the view that women are more susceptible than men to the medical consequences of alcohol abuse. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  2. Role of microRNAs in Alcohol-Induced Multi-Organ Injury

    Sathish Kumar Natarajan

    2015-11-01

    Full Text Available Alcohol consumption and its abuse is a major health problem resulting in significant healthcare cost in the United States. Chronic alcoholism results in damage to most of the vital organs in the human body. Among the alcohol-induced injuries, alcoholic liver disease is one of the most prevalent in the United States. Remarkably, ethanol alters expression of a wide variety of microRNAs that can regulate alcohol-induced complications or dysfunctions. In this review, we will discuss the role of microRNAs in alcoholic pancreatitis, alcohol-induced liver damage, intestinal epithelial barrier dysfunction, and brain damage including altered hippocampus structure and function, and neuronal loss, alcoholic cardiomyopathy, and muscle damage. Further, we have reviewed the role of altered microRNAs in the circulation, teratogenic effects of alcohol, and during maternal or paternal alcohol consumption.

  3. Effect of naltrexone and ondansetron on alcohol cue-induced activation of the ventral striatum in alcohol-dependent people.

    Myrick, Hugh; Anton, Raymond F; Li, Xingbao; Henderson, Scott; Randall, Patrick K; Voronin, Konstantin

    2008-04-01

    Medication for the treatment of alcoholism is currently not particularly robust. Neuroimaging techniques might predict which medications could be useful in the treatment of alcohol dependence. To explore the effect of naltrexone, ondansetron hydrochloride, or the combination of these medications on cue-induced craving and ventral striatum activation. Functional brain imaging was conducted during alcohol cue presentation. Participants were recruited from the general community following media advertisement. Experimental procedures were performed in the magnetic resonance imaging suite of a major training hospital and medical research institute. Ninety non-treatment-seeking alcohol-dependent (by DSM-IV criteria) and 17 social drinking (analysis but intermediate in a region-specific analysis. Consistent with animal data that suggest that both naltrexone and ondansetron reduce alcohol-stimulated dopamine output in the ventral striatum, the current study found evidence that these medications, alone or in combination, could decrease alcohol cue-induced activation of the ventral striatum, consistent with their putative treatment efficacy.

  4. Binge Alcohol Exposure Transiently Changes the Endocannabinoid System: A Potential Target to Prevent Alcohol-Induced Neurodegeneration

    Daniel J. Liput

    2017-11-01

    Full Text Available Excessive alcohol consumption leads to neurodegeneration, which contributes to cognitive decline that is associated with alcohol use disorders (AUDs. The endocannabinoid system has been implicated in the development of AUDs, but little is known about how the neurotoxic effects of alcohol impact the endocannabinoid system. Therefore, the current study investigated the effects of neurotoxic, binge-like alcohol exposure on components of the endocannabinoid system and related N-acylethanolamines (NAEs, and then evaluated the efficacy of fatty acid amide hydrolase (FAAH inhibition on attenuating alcohol-induced neurodegeneration. Male rats were administered alcohol according to a binge model, which resulted in a transient decrease in [3H]-CP-55,940 binding in the entorhinal cortex and hippocampus following two days, but not four days, of treatment. Furthermore, binge alcohol treatment did not change the tissue content of the three NAEs quantified, including the endocannabinoid and anandamide. In a separate study, the FAAH inhibitor, URB597 was administered to rats during alcohol treatment and neuroprotection was assessed by FluoroJade B (FJB staining. The administration of URB597 during binge treatment did not significantly reduce FJB+ cells in the entorhinal cortex or hippocampus, however, a follow up “target engagement” study found that NAE augmentation by URB597 was impaired in alcohol intoxicated rats. Thus, potential alcohol induced alterations in URB597 pharmacodynamics may have contributed to the lack of neuroprotection by FAAH inhibition.

  5. Clay-Alcohol-Water Dispersions: Anomalous Viscosity Changes Due to Network Formation of Clay Nanosheets Induced by Alcohol Clustering.

    Kimura, Yuji; Haraguchi, Kazutoshi

    2017-05-16

    Clay-alcohol-water ternary dispersions were compared with alcohol-water binary mixtures in terms of viscosity and optical absorbance. Aqueous clay dispersions to which lower alcohols (ethanol, 1-propanol, 2-propanol, and tert-butanol) were added exhibited significant viscosity anomalies (maxima) when the alcohol content was 30-55 wt %, as well as optical absorbance anomalies (maxima). The maximum viscosity (η max ) depended strongly on the clay content and varied between 300 and 8000 mPa·s, making it remarkably high compared with the viscosity anomalies (2 mPa·s) observed in alcohol-water binary mixtures. The alcohol content at η max decreased as the hydrophobicity of the alcohol increased. The ternary dispersions with viscosity anomalies exhibited thixotropic behaviors. The effects of other hydrophilic solvents (glycols) and other kinds of clays were also clarified. Based on these findings and the average particle size changes, the viscosity anomalies in the ternary dispersions were explained by alcohol-clustering-induced network formation of the clay nanosheets. It was estimated that 0.9, 1.7, and 2.5 H 2 O molecules per alcohol molecule were required to stabilize the ethanol, 2-propanol, and tert-butanol, respectively, in the clay-alcohol-water dispersions.

  6. Alcohol

    ... because that's how many accidents occur. What Is Alcoholism? What can be confusing about alcohol is that ... develop a problem with it. Sometimes, that's called alcoholism (say: al-kuh-HOL - ism) or being an ...

  7. Alcohol

    If you are like many Americans, you drink alcohol at least occasionally. For many people, moderate drinking ... risky. Heavy drinking can lead to alcoholism and alcohol abuse, as well as injuries, liver disease, heart ...

  8. Alcohol

    Navarro Junior, L.

    1988-01-01

    The alcohol production as a secondary energy source, the participation of the alcohol in Brazilian national economic and social aspects are presented. Statistical data of alcohol demand compared with petroleum by-products and electricity are also included. (author)

  9. Changes in cerebral [18F]-FDG uptake induced by acute alcohol administration in a rat model of alcoholism.

    Gispert, Juan D; Figueiras, Francisca P; Vengeliene, Valentina; Herance, José R; Rojas, Santiago; Spanagel, Rainer

    2017-06-01

    Several [ 18 F]-FDG positron emission tomography (PET) studies in alcoholics have consistently reported decreases in overall brain glucose metabolism at rest and following acute alcohol administration. However, changes in cerebral glucose utilization associated with the transition to addiction are not well understood and require longitudinal translational imaging studies in animal models of alcoholism. Here, we studied brain glucose uptake in alcohol drinking rats in order to provide convergent evidence to what has previously been reported in human studies. Brain glucose metabolism was measured by [ 18 F]-FDG microPET imaging in different male Wistar rat groups: short-term drinking (three months), long-term drinking (twelve months) and alcohol-naïve. Global and regional cerebral glucose uptake was measured at rest and following acute alcohol administration. We showed that alcohol significantly reduced the whole-brain glucose metabolism. This effect was most pronounced in the parietal cortex and cerebellum. Alcohol-induced decreases in brain [ 18 F]-FDG uptake was most apparent in alcohol-naïve rats, less intense in short-term drinkers and absent in long-term drinkers. The latter finding indicates the occurrence of tolerance to the intoxicating effects of alcohol in long-term drinking individuals. In contrast, some regions, like the ventral striatum and entorhinal cortex, showed enhanced metabolic activity, an effect that did not undergo tolerance during long-term alcohol consumption. Our findings are comparable to those described in human studies using the same methodology. We conclude that [ 18 F]-FDG PET studies in rat models of alcoholism provide good translation and can be used for future longitudinal studies investigating alterations in brain function during different stages of the addiction cycle. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Intestinal CYP2E1: A mediator of alcohol-induced gut leakiness

    Christopher B. Forsyth

    2014-01-01

    Full Text Available Chronic alcohol use can result in many pathological effects including alcoholic liver disease (ALD. While alcohol is necessary for the development of ALD, only 20–30% of alcoholics develop alcoholic steatohepatitis (ASH with progressive liver disease leading to cirrhosis and liver failure (ALD. This suggests that while chronic alcohol consumption is necessary it is not sufficient to induce clinically relevant liver damage in the absence of a secondary risk factor. Studies in rodent models and alcoholic patients show that increased intestinal permeability to microbial products like endotoxin play a critical role in promoting liver inflammation in ALD pathogenesis. Therefore identifying mechanisms of alcohol-induced intestinal permeability is important in identifying mechanisms of ALD and for designing new avenues for therapy. Cyp2e1 is a cytochrome P450 enzyme that metabolizes alcohol has been shown to be upregulated by chronic alcohol use and to be a major source of oxidative stress and liver injury in alcoholics and in animal and in vitro models of chronic alcohol use. Because Cyp2e1 is also expressed in the intestine and is upregulated by chronic alcohol use, we hypothesized it could play a role in alcohol-induced intestinal hyperpermeability. Our in vitro studies with intestinal Caco-2 cells and in mice fed alcohol showed that circadian clock proteins CLOCK and PER2 are required for alcohol-induced permeability. We also showed that alcohol increases Cyp2e1 protein and activity but not mRNA in Caco-2 cells and that an inhibitor of oxidative stress or siRNA knockdown of Cyp2e1 prevents the increase in CLOCK or PER2 proteins and prevents alcohol-induced hyperpermeability. With our collaborators we have also shown that Cyp2e1 knockout mice are resistant to alcohol-induced gut leakiness and liver inflammation. Taken together our data support a novel Cyp2e1-circadian clock protein mechanism for alcohol-induced gut leakiness that could provide new

  11. The Effects of Syzygium samarangense, Passiflora edulis and Solanum muricatum on Alcohol-Induced Liver Injury

    Yu-Jie Zhang

    2016-09-01

    Full Text Available Previous studies have shown that fruits have different effects on alcohol metabolism and alcohol-induced liver injury. The present work selected three fruits and aimed at studying the effects of Syzygium samarangense, Passiflora edulis and Solanum muricatum on alcohol-induced liver injury in mice. The animals were treated daily with alcohol and fruit juices for fifteen days. Chronic treatment with alcohol increased the levels of aspartate transaminase (AST, alanine transaminase (ALT, total bilirubin (TBIL, triglyceride (TG, malondialdehyde (MDA, and decreased total protein (TP. Histopathological evaluation also showed that ethanol induced extensive fat droplets in hepatocyte cytoplasm. Syzygium samarangense and Passiflora edulis normalized various biochemical parameters. Solanum muricatum increased the level of ALT and induced infiltration of inflammatory cells in the liver. These results strongly suggest that treatment with Syzygium samarangense and Passiflora edulis could protect liver from the injury of alcohol, while Solanum muricatum could aggravate the damage.

  12. The effects of alcohol on mood induced by an emotional film. A study among women

    van Tilburg, M.A.L.; Vingerhoets, A.J.J.M.

    2002-01-01

    Objective: The present study was designed to investigate the effects of alcohol on women's reactions to a negative mood-inducing stimulus. It is hypothesized that, like in men, alcohol also reduces tension or induces positive mood in women. In addition, we explored whether different mood states were

  13. Cue-induced alcohol-seeking behaviour is reduced by disrupting the reconsolidation of alcohol-related memories.

    von der Goltz, Christoph; Vengeliene, Valentina; Bilbao, Ainhoa; Perreau-Lenz, Stephanie; Pawlak, Cornelius R; Kiefer, Falk; Spanagel, Rainer

    2009-08-01

    In humans, the retrieval of memories associated with an alcohol-related experience frequently evokes alcohol-seeking behaviour. The reconsolidation hypothesis states that a consolidated memory could again become labile and susceptible to disruption after memory retrieval. The aim of our study was to examine whether retrieval of alcohol-related memories undergoes a reconsolidation process. For this purpose, male Wistar rats were trained to self-administer ethanol in the presence of specific conditioned stimuli. Thereafter, animals were left undisturbed in their home cages for the following 21 days. Memory retrieval was performed in a single 5-min exposure to all alcohol-associated stimuli. The protein synthesis inhibitor anisomycin, the non-competitive N-methyl-D: -aspartate (NMDA) receptor antagonist MK-801 and acamprosate, a clinically used drug known to reduce a hyper-glutamatergic state, were given immediately after retrieval of alcohol-related memories. The impact of drug treatment on cue-induced alcohol-seeking behaviour was measured on the following day and 7 days later. Administration of both anisomycin and MK-801 reduced cue-induced alcohol-seeking behaviour, showing that memory reconsolidation was disrupted by these compounds. However, acamprosate had no effect on the reconsolidation process, suggesting that this process is not dependent on a hyper-glutamatergic state but is more related to protein synthesis and NMDA receptor activity. Pharmacological disruption of reconsolidation of alcohol-associated memories can be achieved by the use of NMDA antagonists and protein synthesis inhibitors and may thus provide a potential new therapeutic strategy for the prevention of relapse in alcohol addiction.

  14. Alcohol-Induced Impairment of Balance is Antagonized by Energy Drinks.

    Marczinski, Cecile A; Fillmore, Mark T; Stamates, Amy L; Maloney, Sarah F

    2018-01-01

    The acute administration of alcohol reliably impairs balance and motor coordination. While it is common for consumers to ingest alcohol with other stimulant drugs (e.g., caffeine, nicotine), little is known whether prototypical alcohol-induced balance impairments are altered by stimulant drugs. The purpose of this study was to examine whether the coadministration of a high-caffeine energy drink with alcohol can antagonize expected alcohol-induced increases in body sway. Sixteen social drinkers (of equal gender) participated in 4 separate double-blind dose administration sessions that involved consumption of alcohol and energy drinks, alone and in combination. Following dose administration, participants completed automated assessments of balance stability (both eyes open and eyes closed) measured using the Biosway Portable Balance System. Participants completed several subjective measures including self-reported ratings of sedation, stimulation, fatigue, and impairment. Blood pressure and pulse rate were recorded repeatedly. The acute administration of alcohol increased body sway, and the coadministration of energy drinks antagonized this impairment. When participants closed their eyes, alcohol-induced body sway was similar whether or not energy drinks were ingested. While alcohol administration increased ratings of sedation and fatigue, energy drink administration increased ratings of stimulation and reduced ratings of fatigue. Modest increases in systolic and diastolic blood pressure following energy drink administration were also observed. Visual assessment of balance impairment is frequently used to indicate that an individual has consumed too much alcohol (e.g., as part of police-standardized field sobriety testing or by a bartender assessing when someone should no longer be served more alcohol). The current findings suggest that energy drinks can antagonize alcohol-induced increases in body sway, indicating that future work is needed to determine whether this

  15. Central administration of the anorexigenic peptide neuromedin U decreases alcohol intake and attenuates alcohol-induced reward in rodents.

    Vallöf, Daniel; Ulenius, Lisa; Egecioglu, Emil; Engel, Jörgen A; Jerlhag, Elisabet

    2017-05-01

    By investigating the neurochemical mechanisms through which alcohol activates the brain reward systems, novel treatment strategies for alcohol use disorder (AUD), a chronic relapsing disease, can be developed. In contrast to the common view of the function of gut-brain peptides, such as neuromedin U (NMU), to regulate food intake and appetite, a novel role in reinforcement mediation has been implied. The anorexigenic effects of NMU are mediated via NMU2 receptors, preferably in the arcuate nucleus and paraventricular nucleus. The expression of NMU2 receptors is also expressed in several reward-related areas in the brain, suggesting a role in reward regulation. The present experiments were therefore set up to investigate the effect of intracerebroventricular administration of NMU on alcohol-mediated behaviors in rodents. We found that central administration of NMU attenuated alcohol-induced locomotor stimulation, accumbal dopamine release and the expression of conditioned place preference in mice. In addition, NMU dose dependently decreased alcohol intake in high, but not in low, alcohol-consuming rats. Central NMU administration did not alter the blood alcohol concentrations nor change the corticosterone levels in rodents. Given that AUD is a major health-care challenge causing an enormous cost to society and novel treatment strategies are warranted, our data suggest that NMU analogues deserve to be evaluated as novel treatment of AUD in humans. © 2016 The Authors Addiction Biology published by John Wiley & Sons Ltd.

  16. Congenital malformations in mice induced by addiction to alcohol ...

    Objective: To study the teratogenic effect of either alcohol alone, cocaine alone, or a combination of both alcohol and cocaine on mice foetuses. Design: Eighty pregnant mice were divided into four equal groups. In the first (alcohol) group, the pregnant females were given absolute ethanol at 2.5gm/100 gm twice daily by ...

  17. Death from seizures induced by chronic alcohol abuse--does it exist?

    Christoffersen, S

    2007-01-01

    aetiologies, but in police reports a person known to have seizures is most likely to be reported as suffering from epilepsy. It is a well-known fact that alcoholics have seizures either due to "alcohol-induced epilepsy" or due to withdrawal from drinking. It also seems to be generally accepted that alcoholics...... may die from these seizures. A literature study was performed of deaths due to alcohol-induced seizures, either during withdrawal or as late-onset seizures where the aetiology was established as long time alcohol abuse and a necropsy had shown no other possible cause of death than a seizure. RESULTS......: It was not possible to find any well-documented cases. It is, however, difficult to compare cases in the literature, as there is no generally accepted classification or nomenclature of seizures related to alcohol abuse....

  18. Interstellar Ices and Radiation-induced Oxidations of Alcohols

    Hudson, R. L.; Moore, M. H.

    2018-04-01

    Infrared spectra of ices containing alcohols that are known or potential interstellar molecules are examined before and after irradiation with 1 MeV protons at ∼20 K. The low-temperature oxidation (hydrogen loss) of six alcohols is followed, and conclusions are drawn based on the results. The formation of reaction products is discussed in terms of the literature on the radiation chemistry of alcohols and a systematic variation in their structures. The results from these new laboratory measurements are then applied to a recent study of propargyl alcohol. Connections are drawn between known interstellar molecules, and several new reaction products in interstellar ices are predicted.

  19. Hepatic overproduction of 13-HODE due to ALOX15 upregulation contributes to alcohol-induced liver injury in mice

    Zhang, Wenliang; Zhong, Wei; Sun, Qian; Sun, Xinguo; Zhou, Zhanxiang

    2017-01-01

    Chronic alcohol feeding causes lipid accumulation and apoptosis in the liver. This study investigated the role of bioactive lipid metabolites in alcohol-induced liver damage and tested the potential of targeting arachidonate 15-lipoxygenase (ALOX15) in treating alcoholic liver disease (ALD). Results showed that chronic alcohol exposure induced hepatocyte apoptosis in association with increased hepatic 13-HODE. Exposure of 13-HODE to Hepa-1c1c7 cells induced oxidative stress, ER stress and apo...

  20. Free methionine supplementation limits alcohol-induced liver damage in rats

    Parlesak, Alexandr; Bode, C.; Bode, J.C.

    1998-01-01

    Alcohol feeding to rats that were submitted to a jejunoileal bypass operation has been shown to result in liver damage being comparable with alcohol-induced liver disease in man. In the present study, a striking effect of free methionine consumption on histological liver injury, triglyceride accu...

  1. Host homeostatic responses to alcohol-induced cellular stress in animal models of alcoholic liver disease.

    Wang, He Joe; Murray, Gary J; Jung, Mary Katherine

    2015-01-01

    Humans develop various clinical phenotypes of severe alcoholic liver disease, including alcoholic hepatitis and cirrhosis, generally after decades of heavy drinking. In such individuals, following each episode of drinking, their livers experience heightened intracellular and extracellular stresses that are closely associated with alcohol consumption and alcohol metabolism. This article focuses on the latest advances made in animal models on evolutionarily conserved homeostatic mechanisms for coping with and resolving these stress conditions. The mechanisms discussed include the stress-activated protein kinase JNK, energy regulator AMPK, autophagy and the inflammatory response. Over time, the host may respond variably to stress with protective mechanisms that are critical in determining an individual's vulnerability to developing severe alcoholic liver disease. A systematic review of these mechanisms and their temporal changes in animal models provides the basis for general conclusions, and raises questions for future studies. The relevance of these data to human conditions is also discussed.

  2. [Alcohol].

    Zima, T

    1996-07-14

    Alcohol is one of the most widely used addictive substances. It can be assumed that everybody encounters alcohol--ethanol in various forms and concentrations in the course of their lives. A global and social problem of our civilization is alcohol consumption which has a rising trend. Since 1989 the consumption of alcoholic beverages is rising and the mean annual consumption of concentrated ethanol per head is cea 10 litres. In ethanol abuse the organism is damaged not only by ethanol alone but in particular by substances formed during its metabolism. Its detailed knowledge is essential for the knowledge and investigations of the metabolic and toxic effect of ethanol on the organism. Ingested alcohol is in 90-98% eliminated from the organism by three known metabolic pathways: 1-alcohol dehydrogenase, 2-the microsomal ethanol oxidizing system and 3-catalase. Alcohol is a frequent important risk factor of serious "diseases of civilization" such as IHD, hypertension, osteoporosis, neoplastic diseases. Cirrhosis of the liver and chronic pancreatitis are the well known diseases associated with alcohol ingestion and also their most frequent cause. It is impossible to list all organs and diseases which develop as a result of alcohol consumption. It is important to realize that regular and "relatively" small amounts in the long run damage the organism and may be even fatal.

  3. Mechanisms of Alcohol-Induced Endoplasmic Reticulum Stress and Organ Injuries

    Cheng Ji

    2012-01-01

    Full Text Available Alcohol is readily distributed throughout the body in the blood stream and crosses biological membranes, which affect virtually all biological processes inside the cell. Excessive alcohol consumption induces numerous pathological stress responses, part of which is endoplasmic reticulum (ER stress response. ER stress, a condition under which unfolded/misfolded protein accumulates in the ER, contributes to alcoholic disorders of major organs such as liver, pancreas, heart, and brain. Potential mechanisms that trigger the alcoholic ER stress response are directly or indirectly related to alcohol metabolism, which includes toxic acetaldehyde and homocysteine, oxidative stress, perturbations of calcium or iron homeostasis, alterations of S-adenosylmethionine to S-adenosylhomocysteine ratio, and abnormal epigenetic modifications. Interruption of the ER stress triggers is anticipated to have therapeutic benefits for alcoholic disorders.

  4. Alcoholic beverages induce superconductivity in FeTe1-xSx

    Deguchi, K; Kawasaki, Y; Ozaki, T; Tsuda, S; Yamaguchi, T; Takano, Y; Mizuguchi, Y

    2011-01-01

    We found that hot alcoholic beverages were effective in inducing superconductivity in FeTe 0.8 S 0.2 . Heating the FeTe 0.8 S 0.2 compound in various alcoholic beverages enhances the superconducting properties compared to a pure water-ethanol mixture as a control. Heating with red wine for 24 h leads to the largest shielding volume fraction of 62.4% and the highest zero resistivity temperature of 7.8 K. Some components present in alcoholic beverages, other than water and ethanol, have the ability to induce superconductivity in the FeTe 0.8 S 0.2 compound.

  5. Dietary Fisetin Supplementation Protects Against Alcohol-Induced Liver Injury in Mice.

    Sun, Qian; Zhang, Wenliang; Zhong, Wei; Sun, Xinguo; Zhou, Zhanxiang

    2016-10-01

    Overproduction of reactive oxygen species is associated with the development of alcoholic liver disease (ALD). Plant polyphenols have been used as dietary interventions for multiple diseases including ALD. The objective of this study was to determine whether dietary supplementation with fisetin, a novel flavonoid, exerts beneficial effect on alcohol-induced liver injury. C57BL/6J mice were pair-fed with the Lieber-DeCarli control or ethanol (EtOH) diet for 4 weeks with or without fisetin supplementation at 10 mg/kg/d. Alcohol feeding induced lipid accumulation in the liver and increased plasma alanine aminotransferase and aspartate aminotransferase activities, which were attenuated by fisetin supplementation. The EtOH concentrations in the plasma and liver were significantly elevated by alcohol exposure but were reduced by fisetin supplementation. Although fisetin did not affect the protein expression of alcohol metabolism enzymes, the aldehyde dehydrogenase activities were significantly increased by fisetin compared to the alcohol alone group. In addition, fisetin supplementation remarkably reduced hepatic NADPH oxidase 4 levels along with decreased plasma hydrogen peroxide and hepatic superoxide and 4-hydroxynonenal levels after alcohol exposure. Alcohol-induced apoptosis and up-regulation of Fas and cleaved caspase-3 in the liver were prevented by fisetin. Moreover, fisetin supplementation attenuated alcohol-induced hepatic steatosis through increasing plasma adiponectin levels and hepatic protein levels of p-AMPK, ACOX1, CYP4A, and MTTP. This study demonstrated that the protective effect of fisetin on ALD is achieved by accelerating EtOH clearance and inhibition of oxidative stress. The data suggest that fisetin has a therapeutical potential for treating ALD. Copyright © 2016 by the Research Society on Alcoholism.

  6. Strain-dependent sex differences in the effects of alcohol on cocaine-induced taste aversions.

    Jones, Jermaine D; Busse, Gregory D; Riley, Anthony L

    2006-04-01

    Research using the conditioned taste aversion procedure has reported that a cocaine/alcohol combination induces a significantly stronger taste aversion than either cocaine or alcohol alone. These findings suggest that the co-administration of alcohol intensifies the aversive effects of cocaine. Although the behavioral interaction of cocaine and alcohol is well established, little is known about how the effects of this drug combination might be modulated by a variety of subject variables. The current investigation addressed this by assessing if the ability of alcohol to potentiate cocaine-induced taste aversions is dependent upon the strain and/or sex of the subject. In this series of studies, male and female rats of Long-Evans (Experiment 1) and Sprague-Dawley (Experiment 2) descent were given limited access to a novel saccharin solution to drink and were then injected with either vehicle, cocaine (20 mg/kg), alcohol (0.56 g/kg) or the alcohol/cocaine combination. This procedure was repeated every fourth day for a total of four conditioning trials. All subjects were then compared on an Aversion Test that followed the fourth conditioning cycle. In three of the groups tested (male Long-Evans; male and female Sprague-Dawley), cocaine induced a significant taste aversion that was unaffected by the co-administration of alcohol. However, in female Long-Evans subjects, the addition of alcohol significantly strengthened the avoidance of the saccharin solution. Although the effects of alcohol on cocaine-induced taste aversions are dependent upon an interaction of sex and strain, the basis for this SexxStrain interaction is not known. That such an interaction is evident suggests that attention to such factors in assessing the effects of drug combinations is important to understanding the likelihood of the use and abuse of such drugs.

  7. Genetic Etiology for Alcohol-Induced Cardiac Toxicity.

    Ware, James S; Amor-Salamanca, Almudena; Tayal, Upasana; Govind, Risha; Serrano, Isabel; Salazar-Mendiguchía, Joel; García-Pinilla, Jose Manuel; Pascual-Figal, Domingo A; Nuñez, Julio; Guzzo-Merello, Gonzalo; Gonzalez-Vioque, Emiliano; Bardaji, Alfredo; Manito, Nicolas; López-Garrido, Miguel A; Padron-Barthe, Laura; Edwards, Elizabeth; Whiffin, Nicola; Walsh, Roddy; Buchan, Rachel J; Midwinter, William; Wilk, Alicja; Prasad, Sanjay; Pantazis, Antonis; Baski, John; O'Regan, Declan P; Alonso-Pulpon, Luis; Cook, Stuart A; Lara-Pezzi, Enrique; Barton, Paul J; Garcia-Pavia, Pablo

    2018-05-22

    Alcoholic cardiomyopathy (ACM) is defined by a dilated and impaired left ventricle due to chronic excess alcohol consumption. It is largely unknown which factors determine cardiac toxicity on exposure to alcohol. This study sought to evaluate the role of variation in cardiomyopathy-associated genes in the pathophysiology of ACM, and to examine the effects of alcohol intake and genotype on dilated cardiomyopathy (DCM) severity. The authors characterized 141 ACM cases, 716 DCM cases, and 445 healthy volunteers. The authors compared the prevalence of rare, protein-altering variants in 9 genes associated with inherited DCM. They evaluated the effect of genotype and alcohol consumption on phenotype in DCM. Variants in well-characterized DCM-causing genes were more prevalent in patients with ACM than control subjects (13.5% vs. 2.9%; p = 1.2 ×10 -5 ), but similar between patients with ACM and DCM (19.4%; p = 0.12) and with a predominant burden of titin truncating variants (TTNtv) (9.9%). Separately, we identified an interaction between TTN genotype and excess alcohol consumption in a cohort of DCM patients not meeting ACM criteria. On multivariate analysis, DCM patients with a TTNtv who consumed excess alcohol had an 8.7% absolute reduction in ejection fraction (95% confidence interval: -2.3% to -15.1%; p ACM patients. TTNtv represent a prevalent genetic predisposition for ACM, and are also associated with a worse left ventricular ejection fraction in DCM patients who consume alcohol above recommended levels. Familial evaluation and genetic testing should be considered in patients presenting with ACM. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Alcohol

    ... created when grains, fruits, or vegetables are fermented . Fermentation is a process that uses yeast or bacteria to change the sugars in the food into alcohol. Fermentation is used to produce many necessary items — everything ...

  9. Inhibitory Effects of Pretreatment with Radon on Acute Alcohol-Induced Hepatopathy in Mice

    Teruaki Toyota

    2012-01-01

    Full Text Available We previously reported that radon inhalation activates antioxidative functions in the liver and inhibits carbon tetrachloride-induced hepatopathy in mice. In addition, it has been reported that reactive oxygen species contribute to alcohol-induced hepatopathy. In this study, we examined the inhibitory effects of radon inhalation on acute alcohol-induced hepatopathy in mice. C57BL/6J mice were subjected to intraperitoneal injection of 50% alcohol (5 g/kg bodyweight after inhaling approximately 4000 Bq/m3 radon for 24 h. Alcohol administration significantly increased the activities of glutamic oxaloacetic transaminase (GOT, glutamic pyruvic transaminase (GPT in serum, and the levels of triglyceride and lipid peroxide in the liver, suggesting acute alcohol-induced hepatopathy. Radon inhalation activated antioxidative functions in the liver. Furthermore, pretreatment with radon inhibited the depression of hepatic functions and antioxidative functions. These findings suggested that radon inhalation activated antioxidative functions in the liver and inhibited acute alcohol-induced hepatopathy in mice.

  10. Chronic alcohol feeding potentiates hormone-induced calcium signalling in hepatocytes.

    Bartlett, Paula J; Antony, Anil Noronha; Agarwal, Amit; Hilly, Mauricette; Prince, Victoria L; Combettes, Laurent; Hoek, Jan B; Gaspers, Lawrence D

    2017-05-15

    Chronic alcohol consumption causes a spectrum of liver diseases, but the pathogenic mechanisms driving the onset and progression of disease are not clearly defined. We show that chronic alcohol feeding sensitizes rat hepatocytes to Ca 2+ -mobilizing hormones resulting in a leftward shift in the concentration-response relationship and the transition from oscillatory to more sustained and prolonged Ca 2+ increases. Our data demonstrate that alcohol-dependent adaptation in the Ca 2+ signalling pathway occurs at the level of hormone-induced inositol 1,4,5 trisphosphate (IP 3 ) production and does not involve changes in the sensitivity of the IP 3 receptor or size of internal Ca 2+ stores. We suggest that prolonged and aberrant hormone-evoked Ca 2+ increases may stimulate the production of mitochondrial reactive oxygen species and contribute to alcohol-induced hepatocyte injury. ABSTRACT: 'Adaptive' responses of the liver to chronic alcohol consumption may underlie the development of cell and tissue injury. Alcohol administration can perturb multiple signalling pathways including phosphoinositide-dependent cytosolic calcium ([Ca 2+ ] i ) increases, which can adversely affect mitochondrial Ca 2+ levels, reactive oxygen species production and energy metabolism. Our data indicate that chronic alcohol feeding induces a leftward shift in the dose-response for Ca 2+ -mobilizing hormones resulting in more sustained and prolonged [Ca 2+ ] i increases in both cultured hepatocytes and hepatocytes within the intact perfused liver. Ca 2+ increases were initiated at lower hormone concentrations, and intercellular calcium wave propagation rates were faster in alcoholics compared to controls. Acute alcohol treatment (25 mm) completely inhibited hormone-induced calcium increases in control livers, but not after chronic alcohol-feeding, suggesting desensitization to the inhibitory actions of ethanol. Hormone-induced inositol 1,4,5 trisphosphate (IP 3 ) accumulation and phospholipase C

  11. Thermodynamic and fluorescence studies of the underlying factors in benzyl alcohol-induced lipid interdigitated phase.

    Chen, C H; Hoye, K; Roth, L G

    1996-09-15

    To further investigate factors contributing to the action of alcohol in the solute-induced lipid interdigitation phase, thermodynamic and fluorescence polarization measurements were carried out to study the interaction of benzyl alcohol with dipalmitoyl phosphatidylcholine bilayer vesicles. The obtained results were compared with those previously reported for ethanol and cyclohexanol (L. G. Roth and C-H. Chen, Arch. Biochem. Biophys. 296, 207, 1992). Similar to ethanol, benzyl alcohol was found to exhibit a biphasic effect on the enthalpy (delta Hm) and the temperature (tm) of the lipid-phase transition and the steady-state fluorescence polarization (P) monitored by 1,6-diphenyl-1,3,5-hexatriene. At a total concentration of benzyl alcohol delta Hm and P, which were correlated with the formation of a lipid interdigitated phase, as evidenced by reported X-ray diffraction data. Combining the results with benzyl alcohol and ethanol suggested that simultaneously large changes in delta Hm and P can be used as an indication of the occurrence of a solute-induced lipid interdigitated phase. The overall interacting force in the formation of this lipid phase, as derived from the interactions of the hydroxyl portion of an alcohol with the lipid phosphate head group and the hydrophobic portion of an alcohol with the lipid hydrocarbon chains, may or may not be dominated by hydrophobic interaction. Although lipid/water partition coefficients and the contribution of hydrophobic interaction to the overall interacting force were comparable between benzyl alcohol and cyclohexanol, benzyl alcohol induced lipid interdigitated phase, but not for cyclohexanol. This was due to the ability of benzyl alcohol to be more effective than cyclohexanol in simultaneously interacting with the phosphate head group and the hydrocarbon chains of lipid.

  12. Curcumin confers neuroprotection against alcohol-induced hippocampal neurodegeneration via CREB-BDNF pathway in rats.

    Motaghinejad, Majid; Motevalian, Manijeh; Fatima, Sulail; Hashemi, Hajar; Gholami, Mina

    2017-03-01

    Alcohol abuse causes severe damage to the brain neurons. Studies have reported the neuroprotective effects of curcumin against alcohol-induced neurodegeneration. However, the precise mechanism of action remains unclear. Seventy rats were equally divided into 7 groups (10 rats per group). Group 1 received normal saline (0.7ml/rat) and group 2 received alcohol (2g/kg/day) for 21days. Groups 3, 4, 5 and 6 concurrently received alcohol (2g/kg/day) and curcumin (10, 20, 40 and 60mg/kg, respectively) for 21days. Animals in group 7 self- administered alcohol for 21days. Group 8 treated with curcumin (60mg/kg, i.p.) alone for 21days. Open Field Test (OFT) was used to investigate motor activity in rats. Hippocampal oxidative, antioxidative and inflammatory factors were evaluated. Furthermore, brain cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) and brain derived neurotrophic factor (BDNF) levels were studied at gene level by reverse transcriptase polymerase chain reaction (RT-PCR). In addition, protein expression for BDNF, CREB, phosphorylated CREB (CREB-P), Bax and Bcl-2 was determined by western blotting. Voluntary and involuntary administration of alcohol altered motor activity in OFT, and curcumin treatment inhibited this alcohol-induced motor disturbance. Also, alcohol administration augmented lipid peroxidation, mitochondrial oxidized glutathione (GSSG), interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and Bax levels in isolated hippocampal tissues. Furthermore, alcohol-induced significant reduction were observed in reduced form of glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GR) activities and CREB, BDNF and Bcl-2 levels. Also curcumin alone did not change the behavior and biochemical and molecular parameters. Curcumin can act as a neuroprotective agent against neurodegenerative effects of alcohol abuse, probably via activation of CREB-BDNF signaling pathway

  13. Effect of chronic alcohol ingestion on the progression of periodontitis induced in Fisher-344 rats

    Éder Ricardo Biasoli

    2009-01-01

    Full Text Available Objective: Understand the effect of chronic alcohol on the progression of periodontitis induced in Fischer-344 rats.Methods: For the study, 22 Fischer-344 rats, two months old were used, divided into groups: alcohol (n=8, ligature (n=7 and control (n=7. On the first day, the animals in the alcohol group were exposed to ingestion of a water solution containing 20% alcohol (size/size, up to day 90. After thirty days from the beginning of the experiment, the animals in the alcohol group and the ligature group were submitted to the placement of a silk thread around the right maxillary second molar. Nothing was performed on the left side, serving as control. All the groups were submitted to euthanasia 60 days after ligature placement. To assess the destruction of periodontitis, a radiographic exam was used to measure the destruction of bone height. Results: The results of the study showed that on the side in which periodontitis was induced, the group that ingested alcohol suffered an increase in destruction, with statistical differences when compared with the ligature and control groups and increased bone destruction in the ligature group when compared to control. Conclusion: Within the limitations of the study, it was concluded that chronic alcohol consumption by Fischer-344 rats led to greater progression of induced periodontitis.

  14. Comparative effects of curcumin and an analog of curcumin on alcohol and PUFA induced oxidative stress.

    Rukkumani, Rajagopalan; Aruna, Kode; Varma, Penumathsa Suresh; Rajasekaran, Kallikat Narayanan; Menon, Venugopal Padmanabhan

    2004-08-20

    Alcoholic liver disease is a major medical complication of alcohol abuse and a common liver disease in western countries. Increasing evidence demonstrates that oxidative stress plays an important etiologic role in the development of alcoholic liver disease. Alcohol alone or in combination with high fat is known to cause oxidative injury. The present study therefore aims at evaluating the protective role of curcumin, an active principle of turmeric and a synthetic analog of curcumin (CA) on alcohol and thermally oxidised sunflower oil (DeltaPUFA) induced oxidative stress. Male albino Wistar rats were used for the experimental study. The liver marker enzymes: gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), the lipid peroxidative indices: thiobarbituric acid reactive substances (TBARS) and hydroperoxides (HP) and antioxidants such as vitamin C, vitamin E, reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) were used as biomarkers for testing the antioxidant potential of the drugs. The liver marker enzymes and lipid peroxidative indices were increased significantly in alcohol, DeltaPUFA and alcohol + DeltaPUFA groups. Administration of curcumin and CA abrograted this effect. The antioxidant status which was decreased in alcohol, DeltaPUFA and alcohol + DeltaPUFA groups was effectively modulated by both curcumin and CA treatment. However, the reduction in oxidative stress was more pronounced in CA treatment groups compared to curcumin. In conclusion, these observations show that CA exerts its protective effect by decreasing the lipid peroxidation and improving antioxidant status, thus proving itself as an effective antioxidant.

  15. Protective Effects of Tinospora cordifolia on Hepatic and Gastrointestinal Toxicity Induced by Chronic and Moderate Alcoholism.

    Sharma, Bhawana; Dabur, Rajesh

    2016-01-01

    Heavy alcohol intake depletes the plasma vitamins due to hepatotoxicity and decreased intestinal absorption. However, moderate alcohol intake is often thought to be healthy. Therefore, effects of chronic moderate alcohol intake on liver and intestine were studied using urinary vitamin levels. Furthermore, effects of Tinospora cordifolia water extract (TCE) (hepatoprotective) on vitamin excretion and intestinal absorption were also studied. In the study, asymptomatic moderate alcoholics (n = 12) without chronic liver disease and healthy volunteers (n = 14) of mean age 39 ± 2.2 (mean ± SD) were selected and divided into three groups. TCE treatment was performed for 14 days. The blood and urine samples were collected on Day 0 and 14 after treatment with TCE and analyzed. In alcoholics samples, a significant increase in the levels of gamma-glutamyl transferase, aspartate transaminase, alanine transaminase, Triglyceride, Cholesterol, HDL and LDL (P alcoholic samples; however, TCE intervention restored the CA and biotin levels. Vitamin metabolism biomarkers, i.e. homocysteine and xanthurenic acid, were also normalized after TCE intervention. Overall data depict that moderate alcohol intake is also hepatotoxic and decreases intestinal absorption. However, TCE treatment effectively increased the intestinal absorption and retaining power of liver that regulated alcohol-induced multivitamin deficiency. © The Author 2015. Medical Council on Alcohol and Oxford University Press. All rights reserved.

  16. Lactobacillus rhamnosus CCFM1107 treatment ameliorates alcohol-induced liver injury in a mouse model of chronic alcohol feeding.

    Tian, Fengwei; Chi, Feifei; Wang, Gang; Liu, Xiaoming; Zhang, Qiuxiang; Chen, Yongquan; Zhang, Hao; Chen, Wei

    2015-12-01

    Lactobacillus rhamnosus CCFM1107 was screened for high antioxidative activity from 55 lactobacilli. The present study attempted to explore the protective properties of L. rhamnosus CCFM1107 in alcoholic liver injury. A mouse model was induced by orally feeding alcohol when simultaneously treated with L. rhamnosus CCFM1107, the drug Hu-Gan- Pian (HGP), L. rhamnosus GG (LGG), and L. plantarum CCFM1112 for 3 months. Biochemical analysis was performed for both serum and liver homogenate. Detailed intestinal flora and histological analyses were also carried out. Our results indicated that the administration of L. rhamnosus CCFM1107 significantly inhibited the increase in the levels of serum aminotransferase and endotoxin, as well as the levels of triglyceride (TG) and cholesterol (CHO) in the serum and in the liver. Glutathione (GSH), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were elevated while the levels of malondialdehyde (MDA) were decreased. The enteric dysbiosis caused by alcohol was restored by increasing the numbers of both lactobacilli and bifidobacteria and decreasing the numbers of both enterococci and enterobacter. Histological analysis confirmed the protective effect of L. rhamnosus CCFM1107. Compared with the other lactobacilli and to the drug Hu-Gan-Pian, there is a high chance that L. rhamnosus CCFM1107 provides protective effects on alcoholic liver injury by reducing oxidative stress and restoring the intestinal flora.

  17. Feasibility of Trace Alcohol Congener Detection and Identification Using Laser-Induced Breakdown Spectroscopy

    Zhang Jialiang; Wang Shangmin; Zhao Lixian; Liu Liying; Wang Dezhen

    2014-01-01

    In this paper, a feasible scheme is reported for the detection and identification of trace alcohol congeners that have identical elemental composition using laser-induced breakdown spectroscopy (LIBS). In the scheme, an intensive pulsed laser is used to break down trace alcohol samples and the optical emission spectra of the induced plasma are collected for the detection and identification of alcohol molecules. In order to prepare trace alcohol samples, pure ethanol or methanol is bubbled by argon carrier gas and then mixed into matrix gases. The key issue for the scheme is to constitute indices from the LIBS data of the alcohol samples. Two indices are found to be suitable for alcohol detection and identification. One is the emission intensity ratio (denoted as H/C) of the hydrogen line (653.3 nm) to the carbon line (247.9 nm) for identification and the other is the ratio of the carbon line (as C/Ar) or the hydrogen line (as H/Ar) to the argon lines (866.7 nm) for quantitative detection. The calibration experiment result shows that the index H/C is specific for alcohol congeners while almost being independent of alcohol concentration. In detail, the H/C keeps a specific constant of 34 and 23 respectively for ethanol and methanol. In the meanwhile, the C/Ar and H/Ar indices respond almost linearly to the alcohol concentration below 1300 ppm, and are therefore competent for concentration measurement. With the indices, trace alcohol concentration measurement achieves a limit of 140 ppm using a laser pulse energy of 300 mJ. (plasma technology)

  18. Social transfer of alcohol withdrawal-induced hyperalgesia in female prairie voles.

    Walcott, Andre T; Smith, Monique L; Loftis, Jennifer M; Ryabinin, Andrey E

    2018-03-27

    The expression of pain serves as a way for animals to communicate potential dangers to nearby conspecifics. Recent research demonstrated that mice undergoing alcohol or morphine withdrawal, or inflammation, could socially communicate their hyperalgesia to nearby mice. However, it is unknown whether such social transfer of hyperalgesia can be observed in other species of rodents. Therefore, the present study investigated if the social transfer of hyperalgesia occurs in the highly social prairie vole (Microtus ochrogaster). We observe that adult female prairie voles undergoing withdrawal from voluntary two-bottle choice alcohol drinking display an increase in nociception. This alcohol withdrawal-induced hypersensitiity is socially transferred to female siblings within the same cage and female strangers housed in separate cages within the same room. These experiments reveal that the social transfer of pain phenomenon is not specific to inbred mouse strains and that prairie voles display alcohol withdrawal and social transfer-induced hyperalgesia.

  19. Protective Effects of Lemon Juice on Alcohol-Induced Liver Injury in Mice

    Tong Zhou

    2017-01-01

    Full Text Available Chronic excessive alcohol consumption (more than 40–80 g/day for males and more than 20–40 g/day for females could induce serious liver injury. In this study, effects of lemon juice on chronic alcohol-induced liver injury in mice were evaluated. The serum biochemical profiles and hepatic lipid peroxidation levels, triacylglycerol (TG contents, antioxidant enzyme activities, and histopathological changes were examined for evaluating the hepatoprotective effects of lemon juice in mice. In addition, the in vitro antioxidant capacities of lemon juice were determined. The results showed that lemon juice significantly inhibited alcohol-induced increase of alanine transaminase (ALT, aspartate transaminase (AST, hepatic TG, and lipid peroxidation levels in a dose-dependent manner. Histopathological changes induced by alcohol were also remarkably improved by lemon juice treatment. These findings suggest that lemon juice has protective effects on alcohol-induced liver injury in mice. The protective effects might be related to the antioxidant capacity of lemon juice because lemon juice showed in vitro antioxidant capacity.

  20. Epigenetic Mechanisms in Developmental Alcohol-Induced Neurobehavioral Deficits

    Balapal S. Basavarajappa

    2016-04-01

    Full Text Available Alcohol consumption during pregnancy and its damaging consequences on the developing infant brain are significant public health, social, and economic issues. The major distinctive features of prenatal alcohol exposure in humans are cognitive and behavioral dysfunction due to damage to the central nervous system (CNS, which results in a continuum of disarray that is collectively called fetal alcohol spectrum disorder (FASD. Many rodent models have been developed to understand the mechanisms of and to reproduce the human FASD phenotypes. These animal FASD studies have provided several molecular pathways that are likely responsible for the neurobehavioral abnormalities that are associated with prenatal alcohol exposure of the developing CNS. Recently, many laboratories have identified several immediate, as well as long-lasting, epigenetic modifications of DNA methylation, DNA-associated histone proteins and microRNA (miRNA biogenesis by using a variety of epigenetic approaches in rodent FASD models. Because DNA methylation patterns, DNA-associated histone protein modifications and miRNA-regulated gene expression are crucial for synaptic plasticity and learning and memory, they can therefore offer an answer to many of the neurobehavioral abnormalities that are found in FASD. In this review, we briefly discuss the current literature of DNA methylation, DNA-associated histone proteins modification and miRNA and review recent developments concerning epigenetic changes in FASD.

  1. Anti-apoptotic effects of phyllanthin against alcohol- induced liver ...

    Pretreatment of HepG2 cells and co-cultured cells with phyllanthin for. 24 h prior to alcohol ... Conclusion: The results indicate that phyllanthin treatment may have a significant therapeutic effect on ... process and is dependent upon the interplay of multiple cell ..... Guettier C. Clinical and biological relevance of hepatocyte ...

  2. Sugar alcohols-induced oxidative metabolism in cotton callus culture

    Sugar alcohols (mannitol and sorbitol) may cause oxidative damage in plants if used in higher concentration. Our present experiment was undertaken to study physiological and metabolic responses in cotton (Gossypium hirsutum L.) callus against mannitol and sorbitol higher doses. Both markedly declined mean values of ...

  3. Alcohol

    ... to do. Wondering if adding a glass of wine or beer might help lower your blood glucose if it is high? The effects of alcohol can be unpredictable and it is not recommended as a treatment for high blood glucose. The risks likely outweigh any benefit that may be seen in blood glucose alone. ...

  4. Alcohol consumption in relation to maternal deaths from induced-abortions in Ghana

    Asamoah Benedict O

    2012-08-01

    Full Text Available Abstract Introduction The fight against maternal deaths has gained attention as the target date for Millennium Development Goal 5 approaches. Induced-abortion is one of the leading causes of maternal deaths in developing countries which hamper this effort. In Ghana, alcohol consumption and unwanted pregnancies are on the ascendancy. We examined the association between alcohol consumption and maternal mortality from induced-abortion. We further analyzed the factors that lie behind the alcohol consumption patterns in the study population. Method The data we used was extracted from the Ghana Maternal Health Survey 2007. This was a national survey conducted across the 10 administrative regions of Ghana. The survey identified 4203 female deaths through verbal autopsy, among which 605 were maternal deaths in the 12 to 49 year-old age group. Analysis was done using Statistical software IBM SPSS Statistics 20. A case control study design was used. Cross-tabulations and logistic regression models were used to investigate associations between the different variables. Results Alcohol consumption was significantly associated with abortion-related maternal deaths. Women who had ever consumed alcohol (OR adjusted 2.6, 95% CI 1.38–4.87, frequent consumers (OR adjusted 2.6, 95% CI 0.89–7.40 and occasional consumers (OR adjusted 2.7, 95% CI 1.29–5.46 were about three times as likely to die from abortion-related causes compared to those who abstained from alcohol. Maternal age, marital status and educational level were found to have a confounding effect on the observed association. Conclusion Policy actions directed toward reducing abortion-related deaths should consider alcohol consumption, especially among younger women. Policy makers in Ghana should consider increasing the legal age for alcohol consumption. We suggest that information on the health risks posed by alcohol and abortion be disseminated to communities in the informal sector where

  5. Alcohol-Induced Memory Blackouts as an Indicator of Injury Risk among College Drinkers

    Mundt, Marlon P.; Zakletskaia, Larissa I.; Brown, David D.; Fleming, Michael F.

    2011-01-01

    Objective An alcohol-induced memory blackout represents an amnesia to recall events but does not involve a loss of consciousness. Memory blackouts are a common occurrence among college drinkers, but it is not clear if a history of memory blackouts is predictive of future alcohol-related injury above and beyond the risk associated with heavy drinking episodes. This analysis sought to determine if baseline memory blackouts can prospectively identify college students with alcohol-related injury in the next 24 months after controlling for heavy drinking days. Methods Data were analyzed from the College Health Intervention Project Study (CHIPS), a randomized controlled trial of screening and brief physician intervention for problem alcohol use among 796 undergraduate and 158 graduate students at four university sites in the US and one in Canada, conducted from 2004 to 2009. Multivariate analyses used generalized estimating equations (GEE) with the logit link. Results The overall 24-month alcohol-related injury rate was 25.6%, with no significant difference between males and females (p=.51). Alcohol-induced memory blackouts at baseline exhibited a significant dose-response on odds of alcohol-related injury during follow-up, increasing from 1.57 (95% CI: 1.13–2.19) for subjects reporting 1–2 memory blackouts at baseline to 2.64 (95% CI: 1.65–4.21) for students acknowledging 6+ memory blackouts at baseline. The link between memory blackouts and injury was mediated by younger age, prior alcohol-related injury, heavy drinking, and sensation-seeking disposition. Conclusions Memory blackouts are a significant predictor of future alcohol-related injury among college drinkers after adjusting for heavy drinking episodes. PMID:21708813

  6. Alcohol enhances oxysterol-induced apoptosis in human endothelial cells by a calcium-dependent mechanism.

    Spyridopoulos, I; Wischhusen, J; Rabenstein, B; Mayer, P; Axel, D I; Fröhlich, K U; Karsch, K R

    2001-03-01

    Controversy exists about the net effect of alcohol on atherogenesis. A protective effect is assumed, especially from the tannins and phenolic compounds in red wine, owing to their inhibition of low density lipoprotein (LDL) oxidation. However, increased atherogenesis occurs in subjects with moderate to heavy drinking habits. The purpose of this study was to investigate the influence of alcohol in combination with oxysterols on the endothelium. Cultured human arterial endothelial cells (HAECs) served as an in vitro model to test the cellular effects of various oxysterols. Oxysterols (7beta-hydroxycholesterol, 7-ketocholesterol, and cholesterol-5,6-epoxides), which are assumed to be the most toxic constituents of oxidized LDL, induced apoptosis in HAECs through calcium mobilization followed by activation of caspase-3. Ethanol, methanol, isopropanol, tert-butanol, and red wine all potentiated oxysterol-induced cell death up to 5-fold, paralleled by further induction of caspase-3. The alcohol effect occurred in a dose-dependent manner and reached a plateau at 0.05% concentration. Alcohol itself did not affect endothelial cell viability, nor did other solvents such as dimethyl sulfoxide mimic the alcohol effect. So far as the physiologically occurring oxysterols are concerned, this effect was apparent only for oxysterols oxidized at the steran ring. The possibility of alcohol facilitating the uptake of oxysterols into the cell was not supported by the data from an uptake study with radiolabeled compounds. Finally, alcohol in combination with oxysterols did cause a dramatic increase in cytosolic calcium influx. Blockage of calcium influx by the calcium channel blocker aurintricarboxylic acid or the calcium chelator ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid abrogated the alcohol-mediated enhancement of oxysterol toxicity. We describe for the first time a mechanistic concept explaining possible adverse effects of alcohol in conjunction with

  7. Maltol, a Food Flavoring Agent, Attenuates Acute Alcohol-Induced Oxidative Damage in Mice

    Ye Han

    2015-01-01

    Full Text Available The purpose of this study was to evaluate the hepatoprotective effect of maltol, a food-flavoring agent, on alcohol-induced acute oxidative damage in mice. Maltol used in this study was isolated from red ginseng (Panax ginseng C.A Meyer and analyzed by high performance liquid chromatography (HPLC and mass spectrometry. For hepatoprotective activity in vivo, pretreatment with maltol (12.5, 25 and 50 mg/kg; 15 days drastically prevented the elevated activities of aspartate transaminase (AST, alanine transaminase (ALT, alkaline phosphatase (ALP and triglyceride (TG in serum and the levels of malondialdehyde (MDA, tumor necrosis factor-α (TNF-α, interleukin-1β (IL-1β in liver tissue (p < 0.05. Meanwhile, the levels of hepatic antioxidant, such as catalase (CAT, superoxide dismutase (SOD, glutathione peroxidase (GSH-Px were elevated by maltol pretreatment, compared to the alcohol group (p < 0.05. Histopathological examination revealed that maltol pretreatment significantly inhibited alcohol-induced hepatocyte apoptosis and fatty degeneration. Interestingly, pretreatment of maltol effectively relieved alcohol-induced oxidative damage in a dose-dependent manner. Maltol appeared to possess promising anti-oxidative and anti-inflammatory capacities. It was suggested that the hepatoprotective effect exhibited by maltol on alcohol-induced liver oxidative injury may be due to its potent antioxidant properties.

  8. Aldehyde Dehydrogenase-2 (ALDH2) Ameliorates Chronic Alcohol Ingestion-Induced Myocardial Insulin Resistance and Endoplasmic Reticulum Stress

    Li, Shi-Yan; Gilbert, Sara A.B.; Li, Qun; Ren, Jun

    2009-01-01

    Chronic alcohol intake leads to insulin resistance and alcoholic cardiomyopathy, which appears to be a result of the complex interaction between genes and environment. This study was designed to examine the impact of aldehyde dehydrogenase-2 (ALDH2) transgenic overexpression on alcohol-induced insulin resistance and myocardial injury. ALDH2 transgenic mice were produced using chicken β-actin promoter. Wild-type FVB and ALDH2 mice were fed a 4% alcohol or control diet for 12 wks. Cell shorteni...

  9. Role of hypoxia inducing factor-1β in alcohol-induced autophagy, steatosis and liver injury in mice.

    Hong-Min Ni

    Full Text Available Chronic alcohol causes liver hypoxia and steatosis, which eventually develops into alcoholic liver disease (ALD. While it has been known that alcohol consumption activates hepatic hypoxia inducing factor-1α (HIF-1α, conflicting results regarding the role of HIF-1α in alcohol-induced liver injury and steatosis in mice have been reported. In the present study, we aimed to use hepatocyte-specific HIF-1β knockout mice to eliminate the possible compensatory effects of the single knockout of the 1α subunit of HIF to study the role of HIFs in ALD. C57BL/6 wild type mice were treated with acute ethanol to mimic human binge drinking. Matched wild-type and hepatocyte specific HIF-1β knockout mice were also subjected to a recently established Gao-binge alcohol model to mimic chronic plus binge conditions, which is quite common in human alcoholics. We found that acute alcohol treatment increased BNIP3 and BNIP3L/NIX expression in primary cultured hepatocytes and in mouse livers, suggesting that HIF may be activated in these models. We further found that hepatocyte-specific HIF-1β knockout mice developed less steatosis and liver injury following the Gao-binge model or acute ethanol treatment compared with their matched wild type mice. Mechanistically, protection against Gao-binge treatment-induced steatosis and liver injury was likely associated with increased FoxO3a activation and subsequent induction of autophagy in hepatocyte-specific HIF-1β knockout mice.

  10. Advances and New Concepts in Alcohol-Induced Organelle Stress, Unfolded Protein Responses and Organ Damage

    Cheng Ji

    2015-06-01

    Full Text Available Alcohol is a simple and consumable biomolecule yet its excessive consumption disturbs numerous biological pathways damaging nearly all organs of the human body. One of the essential biological processes affected by the harmful effects of alcohol is proteostasis, which regulates the balance between biogenesis and turnover of proteins within and outside the cell. A significant amount of published evidence indicates that alcohol and its metabolites directly or indirectly interfere with protein homeostasis in the endoplasmic reticulum (ER causing an accumulation of unfolded or misfolded proteins, which triggers the unfolded protein response (UPR leading to either restoration of homeostasis or cell death, inflammation and other pathologies under severe and chronic alcohol conditions. The UPR senses the abnormal protein accumulation and activates transcription factors that regulate nuclear transcription of genes related to ER function. Similarly, this kind of protein stress response can occur in other cellular organelles, which is an evolving field of interest. Here, I review recent advances in the alcohol-induced ER stress response as well as discuss new concepts on alcohol-induced mitochondrial, Golgi and lysosomal stress responses and injuries.

  11. Metabolic response of Candida albicans to phenylethyl alcohol under hyphae-inducing conditions.

    Han, Ting-Li; Tumanov, Sergey; Cannon, Richard D; Villas-Boas, Silas G

    2013-01-01

    Phenylethyl alcohol was one of the first quorum sensing molecules (QSMs) identified in C. albicans. This extracellular signalling molecule inhibits the hyphal formation of C. albicans at high cell density. Little is known, however, about the underlying mechanisms by which this QSM regulates the morphological switches of C. albicans. Therefore, we have applied metabolomics and isotope labelling experiments to investigate the metabolic changes that occur in C. albicans in response to phenylethyl alcohol under defined hyphae-inducing conditions. Our results showed a global upregulation of central carbon metabolism when hyphal development was suppressed by phenylethyl alcohol. By comparing the metabolic changes in response to phenylethyl alcohol to our previous metabolomic studies, we were able to short-list 7 metabolic pathways from central carbon metabolism that appear to be associated with C. albicans morphogenesis. Furthermore, isotope-labelling data showed that phenylethyl alcohol is indeed taken up and catabolised by yeast cells. Isotope-labelled carbon atoms were found in the majority of amino acids as well as in lactate and glyoxylate. However, isotope-labelled carbon atoms from phenylethyl alcohol accumulated mainly in the pyridine ring of NAD(+)/NADH and NADP(-/)NADPH molecules, showing that these nucleotides were the main products of phenylethyl alcohol catabolism. Interestingly, two metabolic pathways where these nucleotides play an important role, nitrogen metabolism and nicotinate/nicotinamide metabolism, were also short-listed through our previous metabolomics works as metabolic pathways likely to be closely associated with C. albicans morphogenesis.

  12. [Effect of Dendrobium officinale granule on long-term-alcohol-induced hypertension rats].

    Lv, Gui-Yuan; Xia, Chao-Qun; Chen, Su-Hong; Su, Jie; Liu, Xiao-Pang; Li, Bo; Gao, Jian-Li

    2013-10-01

    To observe the effect of Dendrobium officinale granule (DOG) on symptoms, blood pressure and serum biochemical indexes of long-term-alcohol-induced hypertension rats. The alcohol-induced hypertension rat model was established by feeding alcohol drink to normal rats (the alcohol volume fraction increases from 5% to 22%). Since the 4th week, DOG was administered for 32 weeks, once everyday. During the experiment, body weight, kinematic parameters (locomotor activities, grip strength, duration of vertigo) and blood pressures (systolic blood pressure, diastolic blood pressure and mean blood pressure) were detected regularly. On the 28th and 32nd weeks, blood samples were collected to determine serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), uric acid (UA), creatinine (Cr), cholesterol (CH) and triglycerides (TG). (1) Sign: The DOG-administered group showed reduction in the duration of vertigo and increase in appetite, body weight, locomotor activities and grip strength. (2) Blood pressure: The DOG-administered group showed significant decrease in blood pressure since the 8th week. (3) Biochemical indexes: The DOG-administered group showed notable decrease in serum ALT, AST, ALP, Cr, UA, TG level, but without significant change in TC level. The long-term administration of DOG can relieve alcohol-induced hypertension, while alleviating general signs, liver and kidney injuries and abnormal blood fat biochemical indexes.

  13. Alcoholic fermentation induces melatonin synthesis in orange juice.

    Fernández-Pachón, M S; Medina, S; Herrero-Martín, G; Cerrillo, I; Berná, G; Escudero-López, B; Ferreres, F; Martín, F; García-Parrilla, M C; Gil-Izquierdo, A

    2014-01-01

    Melatonin (N-acetyl-5-methoxytryptamine) is a molecule implicated in multiple biological functions. Its level decreases with age, and the intake of foods rich in melatonin has been considered an exogenous source of this important agent. Orange is a natural source of melatonin. Melatonin synthesis occurs during alcoholic fermentation of grapes, malt and pomegranate. The amino acid tryptophan is the precursor of all 5-methoxytryptamines. Indeed, melatonin appears in a shorter time in wines when tryptophan is added before fermentation. The aim of the study was to measure melatonin content during alcoholic fermentation of orange juice and to evaluate the role of the precursor tryptophan. Identification and quantification of melatonin during the alcoholic fermentation of orange juice was carried out by UHPLC-QqQ-MS/MS. Melatonin significantly increased throughout fermentation from day 0 (3.15 ng/mL) until day 15 (21.80 ng/mL) reaching larger amounts with respect to other foods. Melatonin isomer was also analysed, but its content remained stable ranging from 11.59 to 14.18 ng/mL. The enhancement of melatonin occurred mainly in the soluble fraction. Tryptophan levels significantly dropped from 13.80 mg/L (day 0) up to 3.19 mg/L (day 15) during fermentation. Melatonin was inversely and significantly correlated with tryptophan (r = 0.907). Therefore, the enhancement in melatonin could be due to both the occurrence of tryptophan and the new synthesis by yeast. In summary, the enhancement of melatonin in novel fermented orange beverage would improve the health benefits of orange juice by increasing this bioactive compound. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Hepcidin regulation in wild-type and Hfe knockout mice in response to alcohol consumption: evidence for an alcohol-induced hypoxic response.

    Heritage, Mandy L; Murphy, Therese L; Bridle, Kim R; Anderson, Gregory J; Crawford, Darrell H G; Fletcher, Linda M

    2009-08-01

    Expression of Hamp1, the gene encoding the iron regulatory peptide hepcidin, is inappropriately low in HFE-associated hereditary hemochromatosis and Hfe knockout mice (Hfe(-/-)). Since chronic alcohol consumption is also associated with disturbances in iron metabolism, we investigated the effects of alcohol consumption on hepcidin mRNA expression in Hfe(-/-) mice. Hfe(-/-) and C57BL/6 (wild-type) mice were pair-fed either an alcohol liquid diet or control diet for up to 8 weeks. The mRNA levels of hepcidin and ferroportin were measured at the mRNA level by RT-PCR and protein expression of hypoxia inducible factor-1 alpha (HIF-1alpha) was measured by western blot. Hamp1 mRNA expression was significantly decreased and duodenal ferroportin expression was increased in alcohol-fed wild-type mice at 8 weeks. Time course experiments showed that the decrease in hepcidin mRNA was not immediate, but was significant by 4 weeks. Consistent with the genetic defect, Hamp1 mRNA was decreased and duodenal ferroportin mRNA expression was increased in Hfe(-/-) mice fed on the control diet compared with wild-type animals and alcohol further exacerbated these effects. HIF-1alpha protein levels were elevated in alcohol-fed wild-type animals compared with controls. Alcohol may decrease Hamp1 gene expression independently of the HFE pathway possibly via alcohol-induced hypoxia.

  15. Visualization of alcohol-induced rhabdomyolysis: a correlative radiotracer, histochemical, and electron-microscopic study

    Silberstein, E.B.; Bove, K.E.

    1979-01-01

    Technetium-99m diphosphonate was used to visualize the extent of alcohol-induced rhabdomyolysis and its resolution. Transient secondary hyperparathyroidism was documented. Histological and biochemical analyses of skeletal muscle obtained at biopsy 6 days postscan and 9 days after the onset of the illness did not show abnormal calcium content

  16. Alcohol dependence induced in rats by semivoluntary intermittent intake

    M.S. Macieira

    1997-09-01

    Full Text Available The objective of the present experiment was to assess ethyl alcohol (ETOH dependence brought about by a semivoluntary intermittent intake regimen in rats. Male Wistar rats weighing 150-250 g at the onset of the experiment were assigned to the following groups: 0% ETOH (N = 11, 5% ETOH (N = 20, 20% ETOH (N = 20 and 40% ETOH (N = 18. ETOH solutions were offered at the end of the day and overnight from Monday to Friday, and throughout weekends, for 90 days. The concentration of the ETOH solutions was increased in a stepwise fashion allowing the rats to get used to the taste of alcohol. Reposition of pure water was permitted during 1-h water drinking periods in the morning. Daily volume intake (± SEM averaged 25.4 ± 0.4 ml (0% ETOH, 23.8 ± 0.6 ml (5% ETOH, 17.6 ± 0.7 ml (20% ETOH and 17.5 ± 0.6 ml (40% ETOH. ETOH consumption differed significantly (P<0.05 among groups, averaging 4.4 ± 0.2 g kg-1 day-1 (5% ETOH, 10.3 ± 0.3 g kg-1 day-1 (20% ETOH and 26 ± 1.2 g kg-1 day-1 (40% ETOH. Furthermore, ETOH detection in plasma 10-12 h after offering the solution indicated that its consumption in the 40% ETOH group was sufficient to override its metabolism. Overt signs of ETOH dependence, such as increased thirst, hyperactivity, puffing, hair ruffling and startle responsiveness as well as reduced drowsiness, were significantly increased in the 20% and 40% ETOH groups compared to the 0% and 5% groups. Accordingly, the model described here proved to be a useful tool for the evaluation of subtle or moderate behavioral and physical consequences of long-term ETOH intake

  17. Amelioration of alcohol-induced hepatotoxicity by the administration of ethanolic extract of Sida cordifolia Linn.

    Rejitha, S; Prathibha, P; Indira, M

    2012-10-01

    Sida cordifolia Linn. (Malvaceae) is a plant used in folk medicine for the treatment of the inflammation of oral mucosa, asthmatic bronchitis, nasal congestion and rheumatism. We studied the hepatoprotective activity of 50 % ethanolic extract of S. cordifolia Linn. against alcohol intoxication. The duration of the experiment was 90 d. The substantially elevated levels of toxicity markers such as alanine aminotransferase, aspartate aminotransferase and γ-glutamyl transferase due to the alcohol treatment were significantly lowered in the extract-treated groups. The activity of antioxidant enzymes and glutathione content, which was lowered due to alcohol toxicity, was increased to a near-normal level in the co-administered group. Lipid peroxidation products, protein carbonyls, total collagen and hydroxyproline, which were increased in the alcohol-treated group, were reduced in the co-administered group. The mRNA levels of cytochrome P450 2E1, NF-κB, TNF-α and transforming growth factor-β1 were found to be increased in the alcohol-treated rats, and their expressions were found to be decreased in the co-administered group. These observations were reinforced by histopathological analysis. Thus, the present study clearly indicates that 50 % ethanolic extract of the roots of S. cordifolia Linn. has a potent hepatoprotective action against alcohol-induced toxicity, which was mediated by lowering oxidative stress and by down-regulating the transcription factors.

  18. DNA Methylation program in normal and alcohol-induced thinning cortex.

    Öztürk, Nail Can; Resendiz, Marisol; Öztürk, Hakan; Zhou, Feng C

    2017-05-01

    While cerebral underdevelopment is a hallmark of fetal alcohol spectrum disorders (FASD), the mechanism(s) guiding the broad cortical neurodevelopmental deficits are not clear. DNA methylation is known to regulate early development and tissue specification through gene regulation. Here, we examined DNA methylation in the onset of alcohol-induced cortical thinning in a mouse model of FASD. C57BL/6 (B6) mice were administered a 4% alcohol (v/v) liquid diet from embryonic (E) days 7-16, and their embryos were harvested at E17, along with isocaloric liquid diet and lab chow controls. Cortical neuroanatomy, neural phenotypes, and epigenetic markers of methylation were assessed using immunohistochemistry, Western blot, and methyl-DNA assays. We report that cortical thickness, neuroepithelial proliferation, and neuronal migration and maturity were found to be deterred by alcohol at E17. Simultaneously, DNA methylation, including 5-methylcytosine (5mC) and 5-hydroxcylmethylcytosine (5hmC), which progresses as an intrinsic program guiding normal embryonic cortical development, was severely affected by in utero alcohol exposure. The intricate relationship between cortical thinning and this DNA methylation program disruption is detailed and illustrated. DNA methylation, dynamic across the multiple cortical layers during the late embryonic stage, is highly disrupted by fetal alcohol exposure; this disruption occurs in tandem with characteristic developmental abnormalities, ranging from structural to molecular. Finally, our findings point to a significant question for future exploration: whether epigenetics guides neurodevelopment or whether developmental conditions dictate epigenetic dynamics in the context of alcohol-induced cortical teratogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Ghrelin knockout mice show decreased voluntary alcohol consumption and reduced ethanol-induced conditioned place preference.

    Bahi, Amine; Tolle, Virginie; Fehrentz, Jean-Alain; Brunel, Luc; Martinez, Jean; Tomasetto, Catherine-Laure; Karam, Sherif M

    2013-05-01

    Recent work suggests that stomach-derived hormone ghrelin receptor (GHS-R1A) antagonism may reduce motivational aspects of ethanol intake. In the current study we hypothesized that the endogenous GHS-R1A agonist ghrelin modulates alcohol reward mechanisms. For this purpose ethanol-induced conditioned place preference (CPP), ethanol-induced locomotor stimulation and voluntary ethanol consumption in a two-bottle choice drinking paradigm were examined under conditions where ghrelin and its receptor were blocked, either using ghrelin knockout (KO) mice or the specific ghrelin receptor (GHS-R1A) antagonist "JMV2959". We showed that ghrelin KO mice displayed lower ethanol-induced CPP than their wild-type (WT) littermates. Consistently, when injected during CPP-acquisition, JMV2959 reduced CPP-expression in C57BL/6 mice. In addition, ethanol-induced locomotor stimulation was lower in ghrelin KO mice. Moreover, GHS-R1A blockade, using JMV2959, reduced alcohol-stimulated locomotion only in WT but not in ghrelin KO mice. When alcohol consumption and preference were assessed using the two-bottle choice test, both genetic deletion of ghrelin and pharmacological antagonism of the GHS-R1A (JMV2959) reduced voluntary alcohol consumption and preference. Finally, JMV2959-induced reduction of alcohol intake was only observed in WT but not in ghrelin KO mice. Taken together, these results suggest that ghrelin neurotransmission is necessary for the stimulatory effect of ethanol to occur, whereas lack of ghrelin leads to changes that reduce the voluntary intake as well as conditioned reward by ethanol. Our findings reveal a major, novel role for ghrelin in mediating ethanol behavior, and add to growing evidence that ghrelin is a key mediator of the effects of multiple abused drugs. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Effectiveness of artichoke extract in preventing alcohol-induced hangovers: a randomized controlled trial

    Pittler, Max H.; White, Adrian R.; Stevinson, Clare; Ernst, Edzard

    2003-01-01

    Background Extract of globe artichoke (Cynara scolymus) is promoted as a possible preventive or cure for alcohol-induced hangover symptoms. However, few rigorous clinical trials have assessed the effects of artichoke extract, and none has examined the effects in relation to hangovers. We undertook this study to test whether artichoke extract is effective in preventing the signs and symptoms of alcohol-induced hangover. Methods We recruited healthy adult volunteers between 18 and 65 years of age to participate in a randomized double-blind crossover trial. Participants received either 3 capsules of commercially available standardized artichoke extract or indistinguishable, inert placebo capsules immediately before and after alcohol exposure. After a 1-week washout period the volunteers received the opposite treatment. Participants predefined the type and amount of alcoholic beverage that would give them a hangover and ate the same meal before commencing alcohol consumption on the 2 study days. The primary outcome measure was the difference in hangover severity scores between the artichoke extract and placebo interventions. Secondary outcome measures were differences between the interventions in scores using a mood profile questionnaire and cognitive performance tests administered 1 hour before and 10 hours after alcohol exposure. Results Fifteen volunteers participated in the study. The mean number (and standard deviation) of alcohol units (each unit being 7.9 g, or 10 mL, of ethanol) consumed during treatment with artichoke extract and placebo was 10.7 (3.1) and 10.5 (2.4) respectively, equivalent to 1.2 (0.3) and 1.2 (0.2) g of alcohol per kilogram body weight. The volume of nonalcoholic drink consumed and the duration of sleep were similar during the artichoke extract and placebo interventions. None of the outcome measures differed significantly between interventions. Adverse events were rare and were mild and transient. Interpretation Our results suggest that

  1. Ethanol up-regulates nucleus accumbens neuronal activity dependent pentraxin (Narp): implications for alcohol-induced behavioral plasticity.

    Ary, Alexis W; Cozzoli, Debra K; Finn, Deborah A; Crabbe, John C; Dehoff, Marlin H; Worley, Paul F; Szumlinski, Karen K

    2012-06-01

    Neuronal activity dependent pentraxin (Narp) interacts with α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) glutamate receptors to facilitate excitatory synapse formation by aggregating them at established synapses. Alcohol is well-characterized to influence central glutamatergic transmission, including AMPA receptor function. Herein, we examined the influence of injected and ingested alcohol upon Narp protein expression, as well as basal Narp expression in mouse lines selectively bred for high blood alcohol concentrations under limited access conditions. Alcohol up-regulated accumbens Narp levels, concomitant with increases in levels of the GluR1 AMPA receptor subunit. However, accumbens Narp or GluR1 levels did not vary as a function of selectively bred genotype. We next employed a Narp knock-out (KO) strategy to begin to understand the behavioral relevance of alcohol-induced changes in protein expression in several assays of alcohol reward. Compared to wild-type mice, Narp KO animals: fail to escalate daily intake of high alcohol concentrations under free-access conditions; shift their preference away from high alcohol concentrations with repeated alcohol experience; exhibit a conditioned place-aversion in response to the repeated pairing of 3 g/kg alcohol with a distinct environment and fail to exhibit alcohol-induced locomotor hyperactivity following repeated alcohol treatment. Narp deletion did not influence the daily intake of either food or water, nor did it alter any aspect of spontaneous or alcohol-induced motor activity, including the development of tolerance to its motor-impairing effects with repeated treatment. Taken together, these data indicate that Narp induction, and presumably subsequent aggregation of AMPA receptors, may be important for neuroplasticity within limbic subcircuits mediating or maintaining the rewarding properties of alcohol. Published by Elsevier Inc.

  2. Alcohol-induced structural transitions in the acid-denatured Bacillus licheniformis α-amylase

    Adyani Azizah Abd Halim

    2017-01-01

    Full Text Available Alcohol-induced structural changes in the acid-denatured Bacillus licheniformis α-amylase (BLA at pH 2.0 were studied by far-ultra violet circular dichroism, intrinsic, three-dimensional and 8-anilino-1-naphthalene sulfonic acid (ANS fluorescence, acrylamide quenching and thermal denaturation. All the alcohols used in this study produced partial refolding in the acid-denatured BLA as evident from the increased mean residue ellipticity at 222 nm, increased intrinsic fluorescence and decreased ANS fluorescence. The order of effectiveness of these alcohols to induce a partially folded state of BLA was found to be: 2,2,2-trifluoroethanol/tert-butanol > 1-propanol/2-propanol > 2-chloroethanol > ethanol > methanol. Three-dimensional fluorescence and acrylamide quenching results obtained in the presence of 5.5 M tert-butanol also suggested formation of a partially folded state in the acid-denatured BLA. However, 5.5 M tert-butanol-induced state of BLA showed a non-cooperative thermal transition. All these results suggested formation of a partially folded state of the acid-denatured BLA in the presence of these alcohols. Furthermore, their effectiveness was found to be guided by their chain length, position of methyl groups and presence of the substituents.

  3. Trace elements in the scalp hair of patients with alcohol induced psychosis

    Pradeep, A.S.; Nagaraju, G.J.; Sarita, P.

    2012-01-01

    A number of essential trace elements play a major role in various metabolic pathways and in many diseases like autoimmune, neurological and psychiatric. This study is undertaken with an aim to evaluate the levels of different trace elements in the scalp hair samples of patients suffering from alcohol induced psychosis by particle induced X-ray emission technique (PIXE). It is observed that Fe (p < 0.0005), Cu (p < 0.001) are significantly higher in the hair samples of alcohol induced psychosis patients compared to those in normals while concentrations of Mn (p < 0.005) and Zn (p < 0.0001) are lower. The concentrations of Co and Ni in the hair samples are found to be in consonance with the concentrations in the normals. (author)

  4. A critical role of lateral hypothalamus in context-induced relapse to alcohol seeking after punishment-imposed abstinence.

    Marchant, Nathan J; Rabei, Rana; Kaganovsky, Konstantin; Caprioli, Daniele; Bossert, Jennifer M; Bonci, Antonello; Shaham, Yavin

    2014-05-28

    In human alcoholics, abstinence is often self-imposed, despite alcohol availability, because of the negative consequences of excessive use. During abstinence, relapse is often triggered by exposure to contexts associated with alcohol use. We recently developed a rat model that captures some features of this human condition: exposure to the alcohol self-administration environment (context A), after punishment-imposed suppression of alcohol self-administration in a different environment (context B), provoked renewal of alcohol seeking in alcohol-preferring P rats. The mechanisms underlying context-induced renewal of alcohol seeking after punishment-imposed abstinence are unknown. Here, we studied the role of the lateral hypothalamus (LH) and its forebrain projections in this effect. We first determined the effect of context-induced renewal of alcohol seeking on Fos (a neuronal activity marker) expression in LH. We next determined the effect of LH reversible inactivation by GABAA + GABAB receptor agonists (muscimol + baclofen) on this effect. Finally, we determined neuronal activation in brain areas projecting to LH during context-induced renewal tests by measuring double labeling of the retrograde tracer cholera toxin subunit B (CTb; injected in LH) with Fos. Context-induced renewal of alcohol seeking after punishment-imposed abstinence was associated with increased Fos expression in LH. Additionally, renewal was blocked by muscimol + baclofen injections into LH. Finally, double-labeling analysis of CTb + Fos showed that context-induced renewal of alcohol seeking after punishment-imposed abstinence was associated with selective activation of accumbens shell neurons projecting to LH. The results demonstrate an important role of LH in renewal of alcohol seeking after punishment-imposed abstinence and suggest a role of accumbens shell projections to LH in this form of relapse. Copyright © 2014 the authors 0270-6474/14/347447-11$15.00/0.

  5. Narcolepsy induced by chronic heavy alcohol consumption: a case report

    Wang, Xinyuan

    2012-01-01

    Summary Narcolepsy is a chronic neurological disorder, characterized by uncontrollable excessive daytime sleepiness, cataplectic episodes, sleep paralysis, hypnagogic hallucinations, and night time sleep disruption. The paper reviewed the related literature and reported a case of long-term drinking induced narcolepsy which was significantly improved after treatment with paroxetine and dexzopiclone. PMID:25328357

  6. Protective Effect of Hericium erinaceus on Alcohol Induced Hepatotoxicity in Mice.

    Hao, Lijun; Xie, Yuxi; Wu, Guikai; Cheng, Aibin; Liu, Xiaogang; Zheng, Rongjuan; Huo, Hong; Zhang, Junwei

    2015-01-01

    We investigated the effects of Hericium erinaceus (HEM) on liver injury induced by acute alcohol administration in mice. Mice received ethanol (5 g/kg BW) by gavage every 12 hrs for a total of 3 doses. HEM (200 mg/kg BW) was gavage before ethanol administration. Subsequent serum alanine aminotransferase (ALT) level, aspartate aminotransaminase (AST) level, Maleic dialdehyde (MDA) level, hepatic total antioxidant status (TAOS), and activated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) were determined by ELISA and immunohistochemistry, respectively. HEM administration markedly (P < 0.05) decreased serum ALT, AST, and MDA levels. The hepatic histopathological observations showed that HEM had a relatively significant role in mice model, which had alcoholic liver damage. In conclusion, we observed that HEM (200 mg/kg BW) supplementation could restrain the hepatic damage caused by acute alcohol exposure.

  7. Protective Effect of Hericium erinaceus on Alcohol Induced Hepatotoxicity in Mice

    Lijun Hao

    2015-01-01

    Full Text Available We investigated the effects of Hericium erinaceus (HEM on liver injury induced by acute alcohol administration in mice. Mice received ethanol (5 g/kg BW by gavage every 12 hrs for a total of 3 doses. HEM (200 mg/kg BW was gavage before ethanol administration. Subsequent serum alanine aminotransferase (ALT level, aspartate aminotransaminase (AST level, Maleic dialdehyde (MDA level, hepatic total antioxidant status (TAOS, and activated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB were determined by ELISA and immunohistochemistry, respectively. HEM administration markedly (P<0.05 decreased serum ALT, AST, and MDA levels. The hepatic histopathological observations showed that HEM had a relatively significant role in mice model, which had alcoholic liver damage. In conclusion, we observed that HEM (200 mg/kg BW supplementation could restrain the hepatic damage caused by acute alcohol exposure.

  8. Protective Effects of Korean Red Ginseng against Alcohol-Induced Fatty Liver in Rats

    Hyo Jin Lee

    2015-06-01

    Full Text Available The present study tested the hypothesis that Korean red ginseng (KRG provides a protective effect against alcoholic fatty liver. Male Sprague-Dawley rats were divided into four groups and fed a modified Lieber-DeCarli diet containing 5% (w/v alcohol or an isocaloric amount of dextrin-maltose for the controls for 6 weeks: normal control (CON, alcohol control (ET, and ET treated with 125 or 250 mg/kg body weight/day of KRG (RGL or RGH, respectively. Compared with the CON group, the ET group exhibited a significant increase in triglycerides, total cholesterol and the presence of lipid droplets in the liver, and a decrease in fat mass, which were all attenuated by KRG supplementation in adose-dependent manner. The mitigation was accompanied by AMP-activated protein kinase (AMPK signaling pathways in the liver and adipose tissue. In addition, suppression in the alcohol-induced changes of adipose adipokine mRNA expression was also observed in KRG supplementation group. These findings suggest that KRG may have the potential to ameliorate alcoholic fatty liver by suppressing inappropriate lysis of adipose tissue and preventing unnecessary de novo lipogenesis in the liver, which are mediated by AMPK signaling pathways. A mechanism for an interplay between the two organs is still needed to be examined with further assays.

  9. Acute Alcohol Intoxication Exacerbates Rhabdomyolysis-Induced Acute Renal Failure in Rats.

    Tsai, Jen-Pi; Lee, Chung-Jen; Subeq, Yi-Maun; Lee, Ru-Ping; Hsu, Bang-Gee

    2017-01-01

    Traumatic and nontraumatic rhabdomyolysis can lead to acute renal failure (ARF), and acute alcohol intoxication can lead to multiple abnormalities of the renal tubules. We examined the effect of acute alcohol intoxication in a rat model of rhabdomyolysis and ARF. Intravenous injections of 5 g/kg ethanol were given to rats over 3 h, followed by glycerol-induced rhabdomyolysis. Biochemical parameters, including blood urea nitrogen (BUN), creatinine (Cre), glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and creatine phosphokinase (CPK), were measured before and after induction of rhabdomyolysis. Renal tissue injury score, renal tubular cell expression of E-cadherin, nuclear factor-κB (NF-κB), and inducible nitric oxide synthase (iNOS) were determined. Relative to rats in the vehicle group, rats in the glycerol-induced rhabdomyolysis group had significantly increased serum levels of BUN, Cre, GOT, GPT, and CPK, elevated renal tissue injury scores, increased expression of NF-κB and iNOS, and decreased expression of E-cadherin. Ethanol exacerbated all of these pathological responses. Our results suggest that acute alcohol intoxication exacerbates rhabdomyolysis-induced ARF through its pro-oxidant and inflammatory effects.

  10. Impact of TLR4 on behavioral and cognitive dysfunctions associated with alcohol-induced neuroinflammatory damage.

    Pascual, María; Baliño, Pablo; Alfonso-Loeches, Silvia; Aragón, Carlos M G; Guerri, Consuelo

    2011-06-01

    Toll-like receptors (TLRs) play an important role in the innate immune response, and emerging evidence indicates their role in brain injury and neurodegeneration. Our recent results have demonstrated that ethanol is capable of activating glial TLR4 receptors and that the elimination of these receptors in mice protects against ethanol-induced glial activation, induction of inflammatory mediators and apoptosis. This study was designed to assess whether ethanol-induced inflammatory damage causes behavioral and cognitive consequences, and if behavioral alterations are dependent of TLR4 functions. Here we show in mice drinking alcohol for 5months, followed by a 15-day withdrawal period, that activation of the astroglial and microglial cells in frontal cortex and striatum is maintained and that these events are associated with cognitive and anxiety-related behavioral impairments in wild-type (WT) mice, as demonstrated by testing the animals with object memory recognition, conditioned taste aversion and dark and light box anxiety tasks. Mice lacking TLR4 receptors are protected against ethanol-induced inflammatory damage, and behavioral associated effects. We further assess the possibility of the epigenetic modifications participating in short- or long-term behavioral effects associated with neuroinflammatory damage. We show that chronic alcohol treatment decreases H4 histone acetylation and histone acetyltransferases activity in frontal cortex, striatum and hippocampus of WT mice. Alterations in chromatin structure were not observed in TLR4(-/-) mice. These results provide the first evidence of the role that TLR4 functions play in the behavioral consequences of alcohol-induced inflammatory damage and suggest that the epigenetic modifications mediated by TLR4 could contribute to short- or long-term alcohol-induced behavioral or cognitive dysfunctions. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Inhibition of Drp-1 dependent mitochondrial fission augments alcohol-induced cardiotoxicity via dysregulated Akt signaling

    Anusha Sivakumar

    2017-10-01

    Full Text Available Cardiovascular disorders (CVDs still claim high mortality in spite of advancements in prognosis and treatment strategies. Alcohol is one of the most commonly consumed drugs globally and chronic/binge consumption (BAC 0.08 g/dL in 2 hours is a risk factor for CVDs. However, the aetiology and pathophysiological mechanisms of alcohol induced cardiotoxicity are still poorly understood. Mitochondria are the prime site for the ATP demands of the heart and also ethanol metabolism. These subcellular organelles depict dynamic fusion and fission events that are vital for structure and functional integrity. While fused mitochondrial improve ATP production and cell survival, increased fragmentation can be the cause or result of apoptosis. In this study, we proposed to analyze the mechanism of mitochondrial fission protein Drp-1-dependent apoptosis during alcohol toxicity. Male Wistar rats (220-250 kg body weight were given isocaloric sucrose or ethanol for 45 days, orally, via drinking water and intermittent gavage twice a week. Histopathological examination of the heart displayed hypertrophy with mild inflammation. Drp-1 immunoblotting showed over-expression of the protein during ethanol treatment. We next hypothesized that inhibiting Drp-1 could attenuate alcohol-induced cardiotoxicity. Interestingly, silencing Drp-1 with siRNA in-vitro augmented cytotoxicity. Also, crude mitochondrial fraction showed increased Bak aggregation, reduced cytochrome c release but increased SMAC/DIABLO. We analyzed the Akt cell survival signaling and found that PTEN showed over-expression at both transcriptional and translational level with no significant change in total Akt but down-regulation of p-Akt (Ser473. In conclusion, we have shown that inhibition of Drp-1 dependent mitochondrial fission is not cardioprotective against alcohol-induced apoptotic signaling and augments the cytotoxicity. To our knowledge, this study is the first to interlink cell survival AKT signaling

  12. Combined effect of selenium and ascorbic acid on alcohol induced hyperlipidemia in male guinea pigs.

    Asha, G S; Indira, M

    2004-02-01

    Alcoholics usually suffer from malnutrition and are especially deficient in micronutrients like vitamin C, selenium and Zn. In the present study, combined effects of selenium and ascorbic acid on alcohol-induced hyperlipidemia were studied in guinea pigs. Four groups of male guinea pigs were maintained for 45 days as follows: control (1 mg ascorbate (AA)/100 g body mass/day), ethanol (900 mg ethanol/100 g body mass + 1 mg AA/100 g body mass/day), selenium+ascorbic acid [(25 mg AA + 0.05 mg Se)/100 g body mass/day], ethanol+selenium+ascorbic acid [(25 mg AA + 0.05 mg Se + 900 mg ethanol)/100 g body mass/day]. Co-administration of selenium and ascorbic acid along with alcohol reduced the concentration of all lipids, as also evidenced from the decreased activities of hydroxymethylglutaryl-CoA reductase and enhanced activities of plasma lecithin cholesterol acyl transferase and lipoprotein lipase. Concentrations of bile acids were increased. We conclude that the supplementation of Se and ascorbic acid reduced alcohol induced hyperlipidemia, by decreased synthesis and increased catabolism.

  13. Hepatic overproduction of 13-HODE due to ALOX15 upregulation contributes to alcohol-induced liver injury in mice.

    Zhang, Wenliang; Zhong, Wei; Sun, Qian; Sun, Xinguo; Zhou, Zhanxiang

    2017-08-21

    Chronic alcohol feeding causes lipid accumulation and apoptosis in the liver. This study investigated the role of bioactive lipid metabolites in alcohol-induced liver damage and tested the potential of targeting arachidonate 15-lipoxygenase (ALOX15) in treating alcoholic liver disease (ALD). Results showed that chronic alcohol exposure induced hepatocyte apoptosis in association with increased hepatic 13-HODE. Exposure of 13-HODE to Hepa-1c1c7 cells induced oxidative stress, ER stress and apoptosis. 13-HODE also perturbed proteins related to lipid metabolism. HODE-generating ALOX15 was up-regulated by chronic alcohol exposure. Linoleic acid, but not ethanol or acetaldehyde, induced ALOX15 expression in Hepa-1c1c7 cells. ALOX15 knockout prevented alcohol-induced liver damage via attenuation of oxidative stress, ER stress, lipid metabolic disorder, and cell death signaling. ALOX15 inhibitor (PD146176) treatment also significantly alleviated alcohol-induced oxidative stress, lipid accumulation and liver damage. These results demonstrated that activation of ALOX15/13-HODE circuit critically mediates the pathogenesis of ALD. This study suggests that ALOX15 is a potential molecular target for treatment of ALD.

  14. Perillyl alcohol suppresses antigen-induced immune responses in the lung

    Imamura, Mitsuru; Sasaki, Oh; Okunishi, Katsuhide; Nakagome, Kazuyuki; Harada, Hiroaki; Kawahata, Kimito; Tanaka, Ryoichi; Yamamoto, Kazuhiko; Dohi, Makoto

    2014-01-01

    Highlights: •Perillyl alcohol (POH) is an isoprenoid which inhibits the mevalonate pathway. •We examined whether POH suppresses immune responses with a mouse model of asthma. •POH treatment during sensitization suppressed Ag-induced priming of CD4 + T cells. •POH suppressed airway eosinophila and cytokine production in thoracic lymph nodes. -- Abstract: Perillyl alcohol (POH) is an isoprenoid which inhibits farnesyl transferase and geranylgeranyl transferase, key enzymes that induce conformational and functional changes in small G proteins to conduct signal production for cell proliferation. Thus, it has been tried for the treatment of cancers. However, although it affects the proliferation of immunocytes, its influence on immune responses has been examined in only a few studies. Notably, its effect on antigen-induced immune responses has not been studied. In this study, we examined whether POH suppresses Ag-induced immune responses with a mouse model of allergic airway inflammation. POH treatment of sensitized mice suppressed proliferation and cytokine production in Ag-stimulated spleen cells or CD4 + T cells. Further, sensitized mice received aerosolized OVA to induce allergic airway inflammation, and some mice received POH treatment. POH significantly suppressed indicators of allergic airway inflammation such as airway eosinophilia. Cytokine production in thoracic lymph nodes was also significantly suppressed. These results demonstrate that POH suppresses antigen-induced immune responses in the lung. Considering that it exists naturally, POH could be a novel preventive or therapeutic option for immunologic lung disorders such as asthma with minimal side effects

  15. Chronic Voluntary Ethanol Consumption Induces Favorable Ceramide Profiles in Selectively Bred Alcohol-Preferring (P Rats.

    Jessica Godfrey

    Full Text Available Heavy alcohol consumption has detrimental neurologic effects, inducing widespread neuronal loss in both fetuses and adults. One proposed mechanism of ethanol-induced cell loss with sufficient exposure is an elevation in concentrations of bioactive lipids that mediate apoptosis, including the membrane sphingolipid metabolites ceramide and sphingosine. While these naturally-occurring lipids serve as important modulators of normal neuronal development, elevated levels resulting from various extracellular insults have been implicated in pathological apoptosis of neurons and oligodendrocytes in several neuroinflammatory and neurodegenerative disorders. Prior work has shown that acute administration of ethanol to developing mice increases levels of ceramide in multiple brain regions, hypothesized to be a mediator of fetal alcohol-induced neuronal loss. Elevated ceramide levels have also been implicated in ethanol-mediated neurodegeneration in adult animals and humans. Here, we determined the effect of chronic voluntary ethanol consumption on lipid profiles in brain and peripheral tissues from adult alcohol-preferring (P rats to further examine alterations in lipid composition as a potential contributor to ethanol-induced cellular damage. P rats were exposed for 13 weeks to a 20% ethanol intermittent-access drinking paradigm (45 ethanol sessions total or were given access only to water (control. Following the final session, tissues were collected for subsequent chromatographic analysis of lipid content and enzymatic gene expression. Contrary to expectations, ethanol-exposed rats displayed substantial reductions in concentrations of ceramides in forebrain and heart relative to non-exposed controls, and modest but significant decreases in liver cholesterol. qRT-PCR analysis showed a reduction in the expression of sphingolipid delta(4-desaturase (Degs2, an enzyme involved in de novo ceramide synthesis. These findings indicate that ethanol intake levels

  16. Protective Effect of Hericium erinaceus on Alcohol Induced Hepatotoxicity in Mice

    Hao, Lijun; Xie, Yuxi; Wu, Guikai; Cheng, Aibin; Liu, Xiaogang; Zheng, Rongjuan; Huo, Hong; Zhang, Junwei

    2015-01-01

    We investigated the effects of Hericium erinaceus (HEM) on liver injury induced by acute alcohol administration in mice. Mice received ethanol (5?g/kg?BW) by gavage every 12?hrs for a total of 3 doses. HEM (200?mg/kg?BW) was gavage before ethanol administration. Subsequent serum alanine aminotransferase (ALT) level, aspartate aminotransaminase (AST) level, Maleic dialdehyde (MDA) level, hepatic total antioxidant status (TAOS), and activated nuclear factor kappa-light-chain-enhancer of activat...

  17. Shanxi Aged Vinegar Protects against Alcohol-Induced Liver Injury via Activating Nrf2-Mediated Antioxidant and Inhibiting TLR4-Induced Inflammatory Response

    Ting Xia

    2018-06-01

    Full Text Available Shanxi aged vinegar (SAV is a typical fermented and antioxidant food, which has various health-promoting effects. This work aimed to explore the effects of SAV on alcohol-induced liver injury. A mice model of alcoholic liver injury was established to illuminate its potential mechanisms. All mice pretreated with SAV and then received an ethanol solution (50% w/v, 4.8 g/kg b.w.. The results showed that SAV ameliorated alcohol-induced histological changes and elevation of liver enzymes. SAV attenuated alcohol-induced oxidative stress by declining levels of hepatic oxidants, and restoring depletion of antioxidant enzyme activities in mice livers. Moreover, SAV alleviated alcohol-induced oxidative damage by activating nuclear factor erythroid-2-related factor 2 (Nrf2-mediated signal pathway. In addition, SAV prevented alcohol-induced inflammation by suppressing lipopolysaccharide (LPS level and activities of pro-inflammatory enzymes, and regulating inflammatory cytokines. SAV inhibited alcohol-induced inflammation through down-regulating the expression of Toll-like receptor 4 (TLR4-mediated inflammatory response. The findings provide crucial evidence for elucidating the hepatoprotective mechanisms of SAV and encourage the future application of SAV as a functional food for liver protection.

  18. Preventive Effects of Forced Exercise against Alcohol-induced Physical Dependency and Reduction of Pain Perception Threshold

    Majid Motaghinejad

    2014-01-01

    Full Text Available Background: Treatment of postabstinence syndrome of alcohol is one of the major strategies of alcoholism treatment. Exercise can be modulated major brain pathways such as a reward system and pain perception centers. The aim of this study was to evaluation the effects of forced exercise in the management of alcohol dependence and pain perception alteration which induced by alcoholism. Methods: 72 adult male rats were divided into 2 major groups: (1 40 of them was divided into groups of positive control (alcohol dependent negative control and alcohol dependent groups under treatment by forced exercise, diazepam (0.4 mg/kg and forced exercise in combination with diazepam and alcohol withdrawal signs, and blood cortisols, were measured in this groups. (2 32 rats were divided into control, alcohol dependent (without treatment, and alcohol-dependent groups under treatment by forced exercise or indometacin (5 mg/kg and then pain perception was assessed by using writhing test, tail-flick and hot plate test. Results: Forced exercise, diazepam, and their combinations significantly attenuates withdrawal syndrome to 20 ± 2, 22 ± 1.3 and 16 ± 2 and blood cortisol level to 6.8 ± 1.3,7.9 ± 1.2 and 5.8 ± 1.1, respectively, in comparison with the positive control group (P < 0.05 and P < 0.001. In alcohol dependent animal under treatment by forced exercise, pain response significantly inhibited with 37%, 57% and 38% decreases in writhing test, hot plate, and tail-flick test, respectively, in comparison with alcohol dependent (without treatment group (P < 0.05. Conclusions: This study suggested that forced exercise can be useful as adjunct therapy in alcoholism patient and also can be effective in modulation of pain threshold reduction that was induced by alcohol dependency.

  19. Regional dependence in earthquake early warning and real time seismology

    Caprio, M.

    2013-01-01

    An effective earthquake prediction method is still a Chimera. What we can do at the moment, after the occurrence of a seismic event, is to provide the maximum available information as soon as possible. This can help in reducing the impact of the quake on population or and better organize the rescue operations in case of post-event actions. This study strives to improve the evaluation of earthquake parameters shortly after the occurrence of a major earthquake, and the characterization of regional dependencies in Real-Time Seismology. The recent earthquake experience from Tohoku (M 9.0, 11.03.2011) showed how an efficient EEW systems can inform numerous people and thus potentially reduce the economic and human losses by distributing warning messages several seconds before the arrival of seismic waves. In the case of devastating earthquakes, usually, in the first minutes to days after the main shock, the common communications channels can be overloaded or broken. In such cases, a precise knowledge of the macroseismic intensity distribution will represent a decisive contribution in help management and in the valuation of losses. In this work, I focused on improving the adaptability of EEW systems (chapters 1 and 2) and in deriving a global relationship for converting peak ground motion into macroseismic intensity and vice versa (chapter 3). For EEW applications, in chapter 1 we present an evolutionary approach for magnitude estimation for earthquake early warning based on real-time inversion of displacement spectra. The Spectrum Inversion (SI) method estimates magnitude and its uncertainty by inferring the shape of the entire displacement spectral curve based on the part of the spectra constrained by available data. Our method can be applied in any region without the need for calibration. SI magnitude and uncertainty estimates are updated each second following the initial P detection and potentially stabilize within 10 seconds from the initial earthquake detection

  20. Regional dependence in earthquake early warning and real time seismology

    Caprio, M.

    2013-07-01

    An effective earthquake prediction method is still a Chimera. What we can do at the moment, after the occurrence of a seismic event, is to provide the maximum available information as soon as possible. This can help in reducing the impact of the quake on population or and better organize the rescue operations in case of post-event actions. This study strives to improve the evaluation of earthquake parameters shortly after the occurrence of a major earthquake, and the characterization of regional dependencies in Real-Time Seismology. The recent earthquake experience from Tohoku (M 9.0, 11.03.2011) showed how an efficient EEW systems can inform numerous people and thus potentially reduce the economic and human losses by distributing warning messages several seconds before the arrival of seismic waves. In the case of devastating earthquakes, usually, in the first minutes to days after the main shock, the common communications channels can be overloaded or broken. In such cases, a precise knowledge of the macroseismic intensity distribution will represent a decisive contribution in help management and in the valuation of losses. In this work, I focused on improving the adaptability of EEW systems (chapters 1 and 2) and in deriving a global relationship for converting peak ground motion into macroseismic intensity and vice versa (chapter 3). For EEW applications, in chapter 1 we present an evolutionary approach for magnitude estimation for earthquake early warning based on real-time inversion of displacement spectra. The Spectrum Inversion (SI) method estimates magnitude and its uncertainty by inferring the shape of the entire displacement spectral curve based on the part of the spectra constrained by available data. Our method can be applied in any region without the need for calibration. SI magnitude and uncertainty estimates are updated each second following the initial P detection and potentially stabilize within 10 seconds from the initial earthquake detection

  1. The Protective Effect of Cordycepin On Alcohol-Induced Osteonecrosis of the Femoral Head

    Yi-Xuan Chen

    2017-08-01

    Full Text Available Background: Alcohol abuse is known to be a leading risk factor for atraumatic osteonecrosis of the femoral head (ONFH, in which the suppression of osteogenesis plays a critical role. Cordycepin benefits bone metabolism; however, there has been no study to determine its effect on osteonecrosis. Methods: Human bone mesenchymal stem cells (hBMSCs were identified by multi-lineage differentiation. Alkaline phosphatase (ALP activity, RT-PCR, western blots, immunofluorescent assay and Alizarin red staining of BMSCs were evaluated. A rat model of alcohol-induced ONFH was established to investigate the protective role of cordycepin against ethanol. Hematoxylin & eosin (H&E staining and micro-computerized tomography (micro-CT were performed to observe ONFH. Apoptosis was assessed by TdT-mediated dUTP nick end labeling (TUNEL. Immunohistochemical staining was carried out to detect OCN and COL1. Results: Ethanol significantly suppressed ALP activity, decreased gene expression of OCN and BMP2, lowered levels of RUNX2 protein, and reduced immunofluorescence staining of OCN and COL1 and calcium formation of hBMSCs. However, these inhibitory effects were attenuated by cordycepin co-treatment at concentrations of 1 and 10 µg/mL Moreover, it was revealed that the osteo-protective effect of cordycepin was associated with modulation of the Wnt/β-catenin pathway. In vivo, by micro-CT, TUNEL and immunohistochemical staining of OCN and COL1, we found that cordycepin administration prevented alcohol-induced ONFH. Conclusion: Cordycepin treatment to enhance osteogenesis may be considered a potential therapeutic approach to prevent the development of alcohol-induced ONFH.

  2. Saturation of retinol-binding protein correlates closely to the severity of alcohol-induced liver disease

    Wagnerberger, S.; Schäfer, C.; Bode, C.

    2006-01-01

    Impaired metabolism of retinol has been shown to occur in alcohol-induced liver disease (ALD). The purpose of the present study was to investigate the saturation of retinol-binding protein (RBP) in 6 patients with different stages of ALD. Hospitalized alcohol consumers (n=118) with different stages......: 43.5+/-6.2%; ALD3: 29.0+/-5.1%). The present study indicates that plasma concentrations of retinol and RBP per se do not correlate to severity of ALD, but rather that the retinol/RBP ratio links to the severity of alcohol-induced liver damage. From these results, a reduced availability of retinol...

  3. The protective role of low-concentration alcohol in high-fructose induced adverse cardiovascular events in mice.

    Wu, Xiaoqi; Pan, Bo; Wang, Ying; Liu, Lingjuan; Huang, Xupei; Tian, Jie

    2018-01-01

    Cardiovascular disease remains a worldwide public health issue. As fructose consumption is dramatically increasing, it has been demonstrated that a fructose-rich intake would increase the risk of cardiovascular disease. In addition, emerging evidences suggest that low concentration alcohol intake may exert a protective effect on cardiovascular system. This study aimed to investigate whether low-concentration alcohol consumption would prevent the adverse effects on cardiovascular events induced by high fructose in mice. From the results of hematoxylin-eosin staining, echocardiography, heart weight/body weight ratio and the expression of hypertrophic marker ANP, we found high-fructose result in myocardial hypertrophy and the low-concentration alcohol consumption would prevent the cardiomyocyte hypertrophy from happening. In addition, we observed low-concentration alcohol consumption could inhibit mitochondria swollen induced by high-fructose. The elevated levels of glucose, triglyceride, total cholesterol in high-fructose group were reduced by low concentration alcohol. Low expression levels of SIRT1 and PPAR-γ induced by high-fructose were significantly elevated when fed with low-concentration alcohol. The histone lysine 9 acetylation (acH3K9) level was decreased in PPAR-γ promoter in high-fructose group but elevated when intake with low concentration alcohol. The binding levels of histone deacetylase SIRT1 were increased in the same region in high-fructose group, while the low concentration alcohol can prevent the increased binding levels. Overall, our study indicates that low-concentration alcohol consumption could inhibit high-fructose related myocardial hypertrophy, cardiac mitochondria damaged and disorders of glucose-lipid metabolism. Furthermore, these findings also provide new insights into histone acetylation-deacetylation mechanisms of low-concentration alcohol treatment that may contribute to the prevention of cardiovascular disease induced by high

  4. Anterior Cingulate Cortex Contributes to Alcohol Withdrawal- Induced and Socially Transferred Hyperalgesia.

    Smith, Monique L; Walcott, Andre T; Heinricher, Mary M; Ryabinin, Andrey E

    2017-01-01

    Pain is often described as a "biopsychosocial" process, yet social influences on pain and underlying neural mechanisms are only now receiving significant experimental attention. Expression of pain by one individual can be communicated to nearby individuals by auditory, visual, and olfactory cues. Conversely, the perception of another's pain can lead to physiological and behavioral changes in the observer, which can include induction of hyperalgesia in "bystanders" exposed to "primary" conspecifics in which hyperalgesia has been induced directly. The current studies were designed to investigate the neural mechanisms responsible for the social transfer of hyperalgesia in bystander mice housed and tested with primary mice in which hyperalgesia was induced using withdrawal (WD) from voluntary alcohol consumption. Male C57BL/6J mice undergoing WD from a two-bottle choice voluntary alcohol-drinking procedure served as the primary mice. Mice housed in the same room served as bystanders. Naïve, water-drinking controls were housed in a separate room. Immunohistochemical mapping identified significantly enhanced Fos immunoreactivity (Fos-ir) in the anterior cingulate cortex (ACC) and insula (INS) of bystander mice compared to naïve controls, and in the dorsal medial hypothalamus (DMH) of primary mice. Chemogenetic inactivation of the ACC but not primary somatosensory cortex reversed the expression of hyperalgesia in both primary and bystander mice. These studies point to an overlapping neural substrate for expression of socially transferred hyperalgesia and that expressed during alcohol WD.

  5. Linking GABA(A) receptor subunits to alcohol-induced conditioned taste aversion and recovery from acute alcohol intoxication.

    Blednov, Y A; Benavidez, J M; Black, M; Chandra, D; Homanics, G E; Rudolph, U; Harris, R A

    2013-04-01

    GABA type A receptors (GABA(A)-R) are important for ethanol actions and it is of interest to link individual subunits with specific ethanol behaviors. We studied null mutant mice for six different GABA(A)-R subunits (α1, α2, α3, α4, α5 and δ). Only mice lacking the α2 subunit showed reduction of conditioned taste aversion (CTA) to ethanol. These results are in agreement with data from knock-in mice with mutation of the ethanol-sensitive site in the α2-subunit (Blednov et al., 2011). All together, they indicate that aversive property of ethanol is dependent on ethanol action on α2-containing GABA(A)-R. Deletion of the α2-subunit led to faster recovery whereas absence of the α3-subunit slowed recovery from ethanol-induced incoordination (rotarod). Deletion of the other four subunits did not affect this behavior. Similar changes in this behavior for the α2 and α3 null mutants were found for flurazepam motor incoordination. However, no differences in recovery were found in motor-incoordinating effects of an α1-selective modulator (zolpidem) or an α4-selective agonist (gaboxadol). Therefore, recovery of rotarod incoordination is under control of two GABA(A)-R subunits: α2 and α3. For motor activity, α3 null mice demonstrated higher activation by ethanol (1 g/kg) whereas both α2 (-/-) and α3 (-/Y) knockout mice were less sensitive to ethanol-induced reduction of motor activity (1.5 g/kg). These studies demonstrate that the effects of ethanol at GABAergic synapses containing α2 subunit are important for specific behavioral effects of ethanol which may be relevant to the genetic linkage of the α2 subunit with human alcoholism. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. LINKING GABAA RECEPTOR SUBUNITS TO ALCOHOL-INDUCED CONDITIONED TASTE AVERSION AND RECOVERY FROM ACUTE ALCOHOL INTOXICATION

    Blednov, Y.A.; Benavidez, J.M.; Black, M.; Chandra, D.; Homanics, G.E.; Rudolph, U.; Harris, R.A.

    2012-01-01

    GABA type A receptors (GABAA-R) are important for ethanol actions and it is of interest to link individual subunits with specific ethanol behaviors. We studied null mutant mice for six different GABAA-R subunits (α1, α2, α3, α4, α5 and δ). Only mice lacking the α2 subunit showed reduction of conditioned taste aversion (CTA) to ethanol. These results are in agreement with data from knock-in mice with mutation of the ethanol-sensitive site in the α2-subunit (Blednov et al., 2011) and indicate this aversive property of ethanol is dependent on ethanol action on α2-containing GABAA-R. Deletion of the α2-subunit led to faster recovery whereas absence of the α3-subunit slowed recovery from ethanol-induced incoordination (rotarod). Deletion of the other four subunits did not affect this behavior. Similar changes in this behavior for the α2 and α3 null mutants were found for flurazepam motor-incoordination. However, no differences in recovery were found in motor-incoordinating effects of an α1-selective modulator (zolpidem) or an α4-selective agonist (gaboxadol). Therefore, recovery of rotarod incoordination is under control of two GABAA-R subunits: α2 and α3. For motor activity, α3 null mice demonstrated higher activation by ethanol (1 g/kg) whereas both α2 and α3 (-/-) knockout mice were less sensitive to ethanol-induced reduction of motor activity (1.5 g/kg). These studies demonstrate that the effects of ethanol at GABAergic synapses containing α2 subunit are important for specific behavioral effects of ethanol which may be relevant to the genetic linkage of the α2 subunit with human alcoholism. PMID:23147414

  7. Distinct cellular responses differentiating alcohol- and hepatitis C virus-induced liver cirrhosis

    Boix Loreto

    2006-11-01

    Full Text Available Abstract Background Little is known at the molecular level concerning the differences and/or similarities between alcohol and hepatitis C virus induced liver disease. Global transcriptional profiling using oligonucleotide microarrays was therefore performed on liver biopsies from patients with cirrhosis caused by either chronic alcohol consumption or chronic hepatitis C virus (HCV. Results Global gene expression patterns varied significantly depending upon etiology of liver disease, with a greater number of differentially regulated genes seen in HCV-infected patients. Many of the gene expression changes specifically observed in HCV-infected cirrhotic livers were expectedly associated with activation of the innate antiviral immune response. We also compared severity (CTP class of cirrhosis for each etiology and identified gene expression patterns that differentiated ethanol-induced cirrhosis by class. CTP class A ethanol-cirrhotic livers showed unique expression patterns for genes implicated in the inflammatory response, including those related to macrophage activation and migration, as well as lipid metabolism and oxidative stress genes. Conclusion Stages of liver cirrhosis could be differentiated based on gene expression patterns in ethanol-induced, but not HCV-induced, disease. In addition to genes specifically regulating the innate antiviral immune response, mechanisms responsible for differentiating chronic liver damage due to HCV or ethanol may be closely related to regulation of lipid metabolism and to effects of macrophage activation on deposition of extracellular matrix components.

  8. Chronic postnatal stress induces voluntary alcohol intake and modifies glutamate transporters in adolescent rats.

    Odeon, María Mercedes; Andreu, Marcela; Yamauchi, Laura; Grosman, Mauricio; Acosta, Gabriela Beatriz

    2015-01-01

    Postnatal stress alters stress responses for life, with serious consequences on the central nervous system (CNS), involving glutamatergic neurotransmission and development of voluntary alcohol intake. Several drugs of abuse, including alcohol and cocaine, alter glutamate transport (GluT). Here, we evaluated effects of chronic postnatal stress (CPS) on alcohol intake and brain glutamate uptake and transporters in male adolescent Wistar rats. For CPS from postnatal day (PD) 7, pups were separated from their mothers and exposed to cold stress (4 °C) for 1 h daily for 20 days; controls remained with their mothers. Then they were exposed to either voluntary ethanol (6%) or dextrose (1%) intake for 7 days (5-7 rats per group), then killed. CPS: (1) increased voluntary ethanol intake, (2) did not affect body weight gain or produce signs of toxicity with alcohol exposure, (3) increased glutamate uptake by hippocampal synaptosomes in vitro and (4) reduced protein levels (Western measurements) in hippocampus and frontal cortex of glial glutamate transporter-1 (GLT-1) and excitatory amino-acid transporter-3 (EAAT-3) but increased glutamate aspartate transporter (GLAST) levels. We propose that CPS-induced decrements in GLT-1 and EAAT-3 expression levels are opposed by activation of a compensatory mechanism to prevent excitotoxicity. A greater role for GLAST in total glutamate uptake to prevent enlarged extracellular glutamate levels is inferred. Although CPS strongly increased intake of ethanol, this had little impact on effects of CPS on brain glutamate uptake or transporters. However, the impact of early life adverse events on glutamatergic neurotransmission may underlie increased alcohol consumption in adulthood.

  9. Effects of Various Drugs on Alcohol-induced Oxidative Stress in the Liver

    Svetlana Trivic

    2008-09-01

    Full Text Available The major aim of this work was to investigate how alcohol-induced oxidative stress in combined chemotherapy changes the metabolic function of the liver in experimental animals. This research was conducted to establish how bromocriptine, haloperidol and azithromycin, applied to the experimental model, affected the antioxidative status of the liver. The following parameters were determined: reduced glutathione, activities of glutathione peroxidase, glutathione reductase, peroxidase, catalase, xanthine oxidase and lipid peroxidation intensity. Alanine transaminase was measured in serum. Alcohol stress (AO group reduced glutathione and the activity of xanthine oxidase and glutathione peroxidase, but increased catalase and alanine transaminase activity. The best protective effect was achieved with the bromocriptine (AB1 group, while other groups had similar effects on the studied parameters.

  10. Protective effects of C-phycocyanin on alcohol-induced acute liver injury in mice

    Xia, Dong; Liu, Bing; Luan, Xiying; Sun, Junyan; Liu, Nana; Qin, Song; Du, Zhenning

    2016-03-01

    Excessive alcohol consumption leads to liver disease. Extensive evidence suggests that C-phycocyanin (C-PC), a chromophore phycocyanobilin derived from Spirulina platensis, exerts protective effects against chemical-induced organ damage. In this study, we investigated whether C-PC could protect against ethanol-induced acute liver injury. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (CHOL), low-density lipoprotein (LDL), liver homogenate malondialdehyde (MDA), superoxide dismutase (SOD) content were measured, and pathological examination of liver sections were examined. C-PC showed obvious inhibitory effects on serum ALT, AST, TG, CHOL, LDL and MDA, and SOD content significantly increased in the liver. The structure of hepatic lobules was clear, liver sinus returned to normal, and liver cell cords were arranged in neat rows. Cloudiness, swelling, inflammatory cell infiltration and spotty necrosis of liver cells were significantly reduced. Therefore, C-PC can significantly protect against ethanol-induced acute liver injury.

  11. Chronic ethanol exposure produces time- and brain region-dependent changes in gene coexpression networks.

    Elizabeth A Osterndorff-Kahanek

    Full Text Available Repeated ethanol exposure and withdrawal in mice increases voluntary drinking and represents an animal model of physical dependence. We examined time- and brain region-dependent changes in gene coexpression networks in amygdala (AMY, nucleus accumbens (NAC, prefrontal cortex (PFC, and liver after four weekly cycles of chronic intermittent ethanol (CIE vapor exposure in C57BL/6J mice. Microarrays were used to compare gene expression profiles at 0-, 8-, and 120-hours following the last ethanol exposure. Each brain region exhibited a large number of differentially expressed genes (2,000-3,000 at the 0- and 8-hour time points, but fewer changes were detected at the 120-hour time point (400-600. Within each region, there was little gene overlap across time (~20%. All brain regions were significantly enriched with differentially expressed immune-related genes at the 8-hour time point. Weighted gene correlation network analysis identified modules that were highly enriched with differentially expressed genes at the 0- and 8-hour time points with virtually no enrichment at 120 hours. Modules enriched for both ethanol-responsive and cell-specific genes were identified in each brain region. These results indicate that chronic alcohol exposure causes global 'rewiring' of coexpression systems involving glial and immune signaling as well as neuronal genes.

  12. Perillyl alcohol suppresses antigen-induced immune responses in the lung

    Imamura, Mitsuru; Sasaki, Oh; Okunishi, Katsuhide; Nakagome, Kazuyuki; Harada, Hiroaki; Kawahata, Kimito; Tanaka, Ryoichi; Yamamoto, Kazuhiko [Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo (Japan); Dohi, Makoto, E-mail: mdohi-tky@umin.ac.jp [Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo (Japan); Institute of Respiratory Immunology, Shibuya Clinic for Respiratory Diseases and Allergology, Tokyo (Japan)

    2014-01-03

    Highlights: •Perillyl alcohol (POH) is an isoprenoid which inhibits the mevalonate pathway. •We examined whether POH suppresses immune responses with a mouse model of asthma. •POH treatment during sensitization suppressed Ag-induced priming of CD4{sup +} T cells. •POH suppressed airway eosinophila and cytokine production in thoracic lymph nodes. -- Abstract: Perillyl alcohol (POH) is an isoprenoid which inhibits farnesyl transferase and geranylgeranyl transferase, key enzymes that induce conformational and functional changes in small G proteins to conduct signal production for cell proliferation. Thus, it has been tried for the treatment of cancers. However, although it affects the proliferation of immunocytes, its influence on immune responses has been examined in only a few studies. Notably, its effect on antigen-induced immune responses has not been studied. In this study, we examined whether POH suppresses Ag-induced immune responses with a mouse model of allergic airway inflammation. POH treatment of sensitized mice suppressed proliferation and cytokine production in Ag-stimulated spleen cells or CD4{sup +} T cells. Further, sensitized mice received aerosolized OVA to induce allergic airway inflammation, and some mice received POH treatment. POH significantly suppressed indicators of allergic airway inflammation such as airway eosinophilia. Cytokine production in thoracic lymph nodes was also significantly suppressed. These results demonstrate that POH suppresses antigen-induced immune responses in the lung. Considering that it exists naturally, POH could be a novel preventive or therapeutic option for immunologic lung disorders such as asthma with minimal side effects.

  13. Lithium prevents long-term neural and behavioral pathology induced by early alcohol exposure.

    Sadrian, B; Subbanna, S; Wilson, D A; Basavarajappa, B S; Saito, M

    2012-03-29

    Fetal alcohol exposure can cause developmental defects in offspring known as fetal alcohol spectrum disorder (FASD). FASD symptoms range from obvious facial deformities to changes in neuroanatomy and neurophysiology that disrupt normal brain function and behavior. Ethanol exposure at postnatal day 7 in C57BL/6 mice induces neuronal cell death and long-lasting neurobehavioral dysfunction. Previous work has demonstrated that early ethanol exposure impairs spatial memory task performance into adulthood and perturbs local and interregional brain circuit integrity in the olfacto-hippocampal pathway. Here we pursue these findings to examine whether lithium prevents anatomical, neurophysiological, and behavioral pathologies that result from early ethanol exposure. Lithium has neuroprotective properties that have been shown to prevent ethanol-induced apoptosis. Here we show that mice co-treated with lithium on the same day as ethanol exposure exhibit dramatically reduced acute neurodegeneration in the hippocampus and retain hippocampal-dependent spatial memory as adults. Lithium co-treatment also blocked ethanol-induced disruption in synaptic plasticity in slice recordings of hippocampal CA1 in the adult mouse brain. Moreover, long-lasting dysfunctions caused by ethanol in olfacto-hippocampal networks, including sensory-evoked oscillations and resting state coherence, were prevented in mice co-treated with lithium. Together, these results provide behavioral and physiological evidence that lithium is capable of preventing or reducing immediate and long-term deleterious consequences of early ethanol exposure on brain function. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

  14. Cue-induced reinstatement of ethanol seeking in Sardinian alcohol-preferring rats.

    Maccioni, Paola; Orrú, Alessandro; Korkosz, Agnieszka; Gessa, Gian Luigi; Carai, Mauro A M; Colombo, Giancarlo; Bienkowski, Przemyslaw

    2007-02-01

    The purpose of the present study was to characterize cue-induced reinstatement of ethanol seeking in selectively bred Sardinian alcohol-preferring (sP) rats trained to lever press for ethanol in 30-min self-administration sessions. Four responses on an "active" lever led to presentation of 0.1 ml of 15% (vol/vol) ethanol by a liquid dipper and concurrent activation of a set of discrete light and auditory cues. In a 70-min extinction/reinstatement session, responding was first extinguished for 60 min. Subsequently, different stimuli were delivered in a noncontingent manner and reinstatement of nonreinforced responding was assessed. Fifteen presentations of the ethanol-predictive stimulus complex, including the dipper cup containing 5 or 15% ethanol, potently reinstated responding on the previously active lever. The magnitude of reinstatement increased with the number of stimulus presentations and concentration of ethanol presented by the dipper cup. Fifteen presentations of the ethanol-predictive stimulus complex, including the dipper cup filled with water (0% ethanol), did not produce any reinstatement. These results indicate that (1) noncontingent presentations of the ethanol-predictive stimulus complex may reinstate ethanol seeking in sP rats and (2) the orosensory properties of ethanol may play an important role in reinstatement of ethanol seeking in sP rats. The latter finding concurs with clinical observations that odor and taste of alcoholic beverages elicit immediate craving responses in abstinent alcoholics.

  15. Involvement of delta opioid receptors in alcohol withdrawal-induced mechanical allodynia in male C57BL/6 mice.

    Alongkronrusmee, Doungkamol; Chiang, Terrance; van Rijn, Richard M

    2016-10-01

    As a legal drug, alcohol is commonly abused and it is estimated that 17 million adults in the United States suffer from alcohol use disorder. Heavy alcoholics can experience withdrawal symptoms including anxiety and mechanical allodynia that can facilitate relapse. The molecular mechanisms underlying this phenomenon are not well understood, which stifles development of new therapeutics. Here we investigate whether delta opioid receptors (DORs) play an active role in alcohol withdrawal-induced mechanical allodynia (AWiMA) and if DOR agonists may provide analgesic relief from AWiMA. To study AWiMA, adult male wild-type and DOR knockout C57BL/6 mice were exposed to alcohol by a voluntary drinking model or oral gavage exposure model, which we developed and validated here. We also used the DOR-selective agonist TAN-67 and antagonist naltrindole to examine the involvement of DORs in AWiMA, which was measured using a von Frey model of mechanical allodynia. We created a robust model of alcohol withdrawal-induced anxiety and mechanical allodynia by orally gavaging mice with 3g/kg alcohol for three weeks. AWiMA was exacerbated and prolonged in DOR knockout mice as well as by pharmacological blockade of DORs compared to control mice. However, analgesia induced by TAN-67 was attenuated during withdrawal in alcohol-gavaged mice. DORs appear to play a protective role in the establishment of AWiMA. Our current results indicate that DORs could be targeted to prevent or reduce the development of AWiMA during alcohol use; however, DORs may be a less suitable target to treat AWiMA during active withdrawal. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. The kinetics of the radiation-induced chain dechlorination of hexachloroethane in alcohols

    Sawai, Takeshi; Ohara, Naoki; Shimokawa, Toshinari

    1978-01-01

    The kinetics of the radiation-induced dechlorination of hexachloroethane was investigated in deoxygenated alcohol solutions. The major products were hydrogen chloride, pentachloroethane, 1,1,2,2-tetrachloroethane, tetrachloroethylene, and aldehydes or acetone. No 1,1,1,2-tetrachloroethane was observed. The radiation-chemical yields of these products and the disappearance of hexachloroethane were quite high; these facts indicate that a chain reaction is involved in these processes. After the hexachloroethane had effectively dechlorinated down to tetrachloro compounds, there were no marked changes in the lower chlorinated compound upon continuous irradiation. Tetrachloroethane was formed via pentachloroethane, but tetrachloroethylene was produced by means of C 2 Cl 5 →C 2 Cl 4 + cl reaction and the yield was particularly high in methanol compared with the other alcohols. The chain length of the dechlorination from hexachloroethane to pentachloroethane and from pentachloroethane to tetrachloroethane increased in the order of 2-propanol>ethanol>methanol. The G(-C 2 Cl 6 ) and G(products) were proportional to (dose rate)sup(-1/2), and the ratio of G(C 2 HCl 5 ) to G(C 2 Cl 4 ) was a constant in each alcohol solution, regardless of the dose rate. The α-hydroxy alkyl radical is the chain carrier for the dechlorination reaction of hexachloroethane in alcohol solutions. The relative rates of the dechlorination were found to be 1, 3, and 14 for C*H 2 OH (*: radical), CH 3 C*HOH (*: radical), and (CH 3 ) 2 C*OH (*: radical), respectively. The order in the rate is in agreement with that of the redox potential of these radicals. The effect of the irradiation temperature on the products yields was also examined. (auth.)

  17. Combined effects of radon inhalation and antioxidant vitamin administration on acute alcohol-induced hepatopathy in mice

    Etani, Reo; Kataoka, Takahiro; Nishiyama, Yuichi; Takata, Yuji; Yamaoka, Kiyonori

    2015-01-01

    It has been reported that radon inhalation activates antioxidative functions in liver and has an antioxidative effect against hepatopathy similar to that of the antioxidative effects of ascorbic acid (VC) or α-tocopherol (VE). In this study, we examined the combined effects of radon inhalation and antioxidant vitamin administration on acute alcohol-induced hepatopathy in mice. ICR mice were subjected to intraperitoneal (i.p.) administration of alcohol after pretreating with air only (sham) or radon at a concentration of approximately 2000 Bq/m 3 for 24 hours and i.p. administration of VC (300 mg/kg body weight) or VE (300 mg/kg body weight). In mice injected with alcohol, the combined radon and antioxidant vitamins treatment significantly decreased the activities of glutamic oxaloacetic transaminase in serum compared to not only the alcohol-administered group (sham group), but also the radon inhalation with alcohol administration group or the vitamin and alcohol administration group. In addition, radon inhalation significantly increased the antioxidant level, in such as the catalase activity and the total glutathione content in liver compared to the sham group. These results suggested that the combined radon and antioxidant vitamin treatment could effectively inhibit alcohol-induced hepatopathy in mice without any antagonizing action. (author)

  18. Maternal L-glutamine supplementation prevents prenatal alcohol exposure-induced fetal growth restriction in an ovine model.

    Sawant, Onkar B; Wu, Guoyao; Washburn, Shannon E

    2015-06-01

    Prenatal alcohol exposure is known to cause fetal growth restriction and disturbances in amino acid bioavailability. Alterations in these parameters can persist into adulthood and low birth weight can lead to altered fetal programming. Glutamine has been associated with the synthesis of other amino acids, an increase in protein synthesis and it is used clinically as a nutrient supplement for low birth weight infants. The aim of this study was to explore the effect of repeated maternal alcohol exposure and L-glutamine supplementation on fetal growth and amino acid bioavailability during the third trimester-equivalent period in an ovine model. Pregnant sheep were randomly assigned to four groups, saline control, alcohol (1.75-2.5 g/kg), glutamine (100 mg/kg, three times daily) or alcohol + glutamine. In this study, a weekend binge drinking model was followed where treatment was done 3 days per week in succession from gestational day (GD) 109-132 (normal term ~147). Maternal alcohol exposure significantly reduced fetal body weight, height, length, thoracic girth and brain weight, and resulted in decreased amino acid bioavailability in fetal plasma and placental fluids. Maternal glutamine supplementation successfully mitigated alcohol-induced fetal growth restriction and improved the bioavailability of glutamine and glutamine-related amino acids such as glycine, arginine, and asparagine in the fetal compartment. All together, these findings show that L-glutamine supplementation enhances amino acid availability in the fetus and prevents alcohol-induced fetal growth restriction.

  19. miR-339-5p inhibits alcohol-induced brain inflammation through regulating NF-κB pathway

    Zhang, Yu; Wei, Guangkuan; Di, Zhiyong; Zhao, Qingjie

    2014-01-01

    Graphical abstract: - Highlights: • Alcohol upregulates miR-339-5p expression. • miR-339-5p inhibits the NF-kB pathway. • miR-339-5p interacts with and blocks activity of IKK-beat and IKK-epsilon. • miR-339-5p modulates IL-1β, IL-6 and TNF-α. - Abstract: Alcohol-induced neuroinflammation is mediated by the innate immunesystem. Pro-inflammatory responses to alcohol are modulated by miRNAs. The miRNA miR-339-5p has previously been found to be upregulated in alcohol-induced neuroinflammation. However, little has been elucidated on the regulatory functions of this miRNA in alcohol-induced neuroinflammation. We investigated the function of miR-339-5p in alcohol exposed brain tissue and isolated microglial cells using ex vivo and in vitro techniques. Our results show that alcohol induces transcription of miR 339-5p, IL-6, IL-1β and TNF-α in mouse brain tissue and isolated microglial cells by activating NF-κB. Alcohol activation of NF-κB allows for nuclear translocation of the NF-κB subunit p65 and expression of pro-inflammatory mediators. miR-339-5p inhibited expression of these pro-inflammatory factors through the NF-κB pathway by abolishing IKK-β and IKK-ε activity

  20. miR-339-5p inhibits alcohol-induced brain inflammation through regulating NF-κB pathway

    Zhang, Yu [Department of Neurology, The First Affiliated School of Harbin Medical University, Harbin 150001 (China); Wei, Guangkuan [Department of Neurology, Heilongjiang Provincial Hospital, Harbin 150036 (China); Di, Zhiyong [Department of Laboratory, Heilongjiang Provincial Hospital, Harbin 150036 (China); Zhao, Qingjie, E-mail: zhaoqingjie2013@163.com [Department of Neurology, The First Affiliated School of Harbin Medical University, Harbin 150001 (China)

    2014-09-26

    Graphical abstract: - Highlights: • Alcohol upregulates miR-339-5p expression. • miR-339-5p inhibits the NF-kB pathway. • miR-339-5p interacts with and blocks activity of IKK-beat and IKK-epsilon. • miR-339-5p modulates IL-1β, IL-6 and TNF-α. - Abstract: Alcohol-induced neuroinflammation is mediated by the innate immunesystem. Pro-inflammatory responses to alcohol are modulated by miRNAs. The miRNA miR-339-5p has previously been found to be upregulated in alcohol-induced neuroinflammation. However, little has been elucidated on the regulatory functions of this miRNA in alcohol-induced neuroinflammation. We investigated the function of miR-339-5p in alcohol exposed brain tissue and isolated microglial cells using ex vivo and in vitro techniques. Our results show that alcohol induces transcription of miR 339-5p, IL-6, IL-1β and TNF-α in mouse brain tissue and isolated microglial cells by activating NF-κB. Alcohol activation of NF-κB allows for nuclear translocation of the NF-κB subunit p65 and expression of pro-inflammatory mediators. miR-339-5p inhibited expression of these pro-inflammatory factors through the NF-κB pathway by abolishing IKK-β and IKK-ε activity.

  1. Landolphia owariensis Attenuates Alcohol-induced Cerebellar Neurodegeneration: Significance of Neurofilament Protein Alteration in the Purkinje Cells

    Oyinbo Charles A.

    2016-12-01

    Full Text Available Background: Alcohol-induced cerebellar neurodegeneration is a neuroadaptation that is associated with chronic alcohol abuse. Conventional drugs have been largely unsatisfactory in preventing neurodegeneration. Yet, multimodal neuro-protective therapeutic agents have been hypothesised to have high therapeutic potential for the treatment of CNS conditions; there is yet a dilemma of how this would be achieved. Contrarily, medicinal botanicals are naturally multimodal in their mechanism of action.

  2. Is nutrient intake a gender-specific cause for enhanced susceptibility to alcohol-induced liver disease in women?

    Wagnerberger, S.; Schäfer, C.; Schwarz, E.

    2008-01-01

    AIM: Women have a higher susceptibility to alcohol-induced liver disease (ALD) than men. Gender-related differences in food preference were described in previous studies for several populations, but not in alcohol abusers. As certain micronutrients are reported to take influence on the development......, the data of calculated daily macro- and micronutrient intake do not suggest any explicit influence of gender-specific nutrition in the development of ALD....

  3. Pathological mechanisms of alcohol-induced hepatic portal hypertension in early stage fibrosis rat model.

    Li, Jian; Niu, Jian-Zhao; Wang, Ji-Feng; Li, Yu; Tao, Xiao-Hua

    2005-11-07

    To study the role of hepatic sinusoidal capillarization and perisinusoidal fibrosis in rats with alcohol-induced portal hypertension and to discuss the pathological mechanisms of alcohol-induced hepatic portal hypertension. Fifty SD rats were divided into control group (n=20) and model group (n=30). Alcoholic liver fibrosis rat model was induced by intragastric infusion of a mixture containing alcohol, corn oil and pyrazole (1 000:250:3). Fifteen rats in each group were killed at wk 16. The diameter and pressure of portal vein were measured. Plasma hyaluronic acid (HA), type IV collagen (CoIV) and laminin (LN) were determined by radioimmunoassay. Liver tissue was fixed in formalin (10%) and 6-mum thick sections were routinely stained with Mallory and Sirius Red. Liver tissue was treated with rabbit polyclonal antibody against LN and ColIV. Hepatic non-parenchymal cells were isolated, total protein was extracted and separated by SDS-PAGE. MMP-2 and TIMP-1 protein expression was estimated by Western blotting. The diameter (2.207+/-0.096 vs 1.528+/-0.054 mm, Pportal vein were significantly higher in model group than those in the control group. Plasma HA (129.97+/-16.10 vs 73.09+/-2.38 ng/mL, Pmodel group. Abundant collagen deposited around the central vein of lobules, hepatic sinusoids and hepatocytes in model group. ColI and ColIII increased remarkably and perisinusoids were almost surrounded by ColIII. Immunohistochemical staining showed that ColIV protein level (0.130+/-0.007 vs 0.032+/-0.004, Pprotein level (0.152+/-0.005 vs 0.029+/-0.005, Pmodel group. MMP-2 protein expression (2.306+/-1.089 vs 0.612+/-0.081, Pprotein expression (3.015+/-1.364 vs 0.446+/-0.009, Pmodel group and TIMP-1 protein expression was evidently higher than MMP-2 protein expression (2.669+/-0.170 vs 1.695+/-0.008, Pportal hypertension in rats.

  4. Alcohol Induced Hepatic Degeneration in a Hepatitis C Virus Core Protein Transgenic Mouse Model

    Dong-Hyung Noh

    2014-03-01

    Full Text Available Hepatitis C virus (HCV has become a major public health issue. It is prevalent in most countries. HCV infection frequently begins without clinical symptoms, before progressing to persistent viremia, chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC in the majority of patients (70% to 80%. Alcohol is an independent cofactor that accelerates the development of HCC in chronic hepatitis C patients. The purpose of the current study was to evaluate ethanol-induced hepatic changes in HCV core-Tg mice and mutant core Tg mice. Wild type (NTG, core wild-Tg mice (TG-K, mutant core 116-Tg mice (TG-116 and mutant core 99-Tg mice (TG-99 were used in this investigation. All groups were given drinking water with 10% ethanol and 5% sucrose for 13 weeks. To observe liver morphological changes, we performed histopathological and immunohistochemical examinations. Histopathologically, NTG, TG-K and TG-116 mice showed moderate centrilobular necrosis, while severe centrilobular necrosis and hepatocyte dissociation were observed in TG-99 mice with increasing lymphocyte infiltration and piecemeal necrosis. In all groups, a small amount of collagen fiber was found, principally in portal areas. None of the mice were found to have myofibroblasts based on immunohistochemical staining specific for α-SMA. CYP2E1-positive cells were clearly detected in the centrilobular area in all groups. In the TG-99 mice, we also observed cells positive for CK8/18, TGF-β1 and phosphorylated (p-Smad2/3 and p21 around the necrotic hepatocytes in the centrilobular area (p < 0.01. Based on our data, alcohol intake induced piecemeal necrosis and hepatocyte dissociation in the TG-99 mice. These phenomena involved activation of the TGF-β1/p-Smad2/3/p21 signaling pathway in hepatocytes. Data from this study will be useful for elucidating the association between alcohol intake and HCV infection.

  5. Stress-induced and cue-induced craving for alcohol in heavy drinkers: Preliminary evidence of genetic moderation by the OPRM1 and CRH-BP genes.

    Ray, Lara A

    2011-01-01

    Neurobiological theories of addiction have highlighted disruption in stress pathways as a central feature of addictive disorders, and pharmacological treatments targeting stress mechanisms hold great promise. This study examines genetic determinants of stress-induced and cue-induced craving in heavy drinkers by testing single-nucleotide polymorphisms (SNPs) of the corticotrophin-releasing hormone binding protein (CRH-BP) gene and the mu-opioid receptor (OPRM1) gene. This study combines guided imagery stress exposure and in vivo alcohol cue exposure in a sample of 64 (23 women) non-treatment-seeking heavy drinkers. Analyses, uncorrected for multiple comparisons, revealed that a tag SNP of the CRH-BP gene (rs10055255) moderated stress-induced craving in this sample. The same SNP predicted greater affective responses to the stress manipulation, including greater levels of subjective tension and negative mood. The Asp40 allele of the OPRM1 was associated with greater cue-induced alcohol craving following the neutral imagery condition. These initial results extend recent preclinical and clinical findings implicating the CRH-BP in stress-related alcoholism and confirm the role of the Asp40 allele of the OPRM1 gene in reward-driven alcohol phenotypes. Human laboratory models of stress and cue-induced craving may be useful in pharmacotherapy development targeting dysregulation of stress systems. Larger studies are needed to validate these preliminary findings, which should also be extended to clinical samples. Copyright © 2010 by the Research Society on Alcoholism.

  6. Alteration of BRCA1 expression affects alcohol-induced transcription of RNA Pol III-dependent genes.

    Zhong, Qian; Shi, Ganggang; Zhang, Yanmei; Lu, Lei; Levy, Daniel; Zhong, Shuping

    2015-02-01

    Emerging evidence has indicated that alcohol consumption is an established risk factor for breast cancer. Deregulation of RNA polymerase III (Pol III) transcription enhances cellular Pol III gene production, leading to an increase in translational capacity to promote cell transformation and tumor formation. We have reported that alcohol intake increases Pol III gene transcription to promote cell transformation and tumor formation in vitro and in vivo. Studies revealed that tumor suppressors, pRb, p53, PTEN and Maf1 repress the transcription of Pol III genes. BRCA1 is a tumor suppressor and its mutation is tightly related to breast cancer development. However, it is not clear whether BRCA1 expression affects alcohol-induced transcription of Pol III genes. At the present studies, we report that restoring BRCA1 in HCC 1937 cells, which is a BRCA1 deficient cell line, represses Pol III gene transcription. Expressing mutant or truncated BRCA1 in these cells does not affect the ability of repression on Pol III genes. Our analysis has demonstrated that alcohol induces Pol III gene transcription. More importantly, overexpression of BRCA1 in estrogen receptor positive (ER+) breast cancer cells (MCF-7) decreases the induction of tRNA(Leu) and 5S rRNA genes by alcohol, whereas reduction of BRCA1 by its siRNA slightly increases the transcription of the class of genes. This suggests that BRCA1 is associated with alcohol-induced deregulation of Pol III genes. These studies for the first time demonstrate the role of BRCA1 in induction of Pol III genes by alcohol and uncover a novel mechanism of alcohol-associated breast cancer. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Voluntary Ingestion of Natural Cocoa Extenuated Hepatic Damage in Rats with Experimentally Induced Chronic Alcoholic Toxicity

    Godwin Sokpor

    2012-05-01

    animals that drank water.Conclusions: Ethanol-induced structural liver injury was qualitatively and quantitatively milder in rats which chronically imbibed alcohol then afterward drank NCP beverage in place of water. The antioxidant and anti-inflammatory properties of polyphenols in NCP are postulated in mitigating the damage of rat liver due to chronic ethanol consumption. Thus, it is suggested from these findings that regular drinking of NCP beverage may slow progression of alcoholic liver disease in dipsomaniacs.

  8. Brain-specific inactivation of the Crhr1 gene inhibits post-dependent and stress-induced alcohol intake, but does not affect relapse-like drinking

    Molander, Anna; Vengeliene, Valentina; Heilig, Markus

    2012-01-01

    , a conditional brain-specific Crhr1-knockout (Crhr1(NestinCre)) and a global knockout mouse line were studied for basal alcohol drinking, stress-induced alcohol consumption, deprivation-induced intake, and escalated alcohol consumption in the post-dependent state. In a second set of experiments, we tested CRHR1...... not affect relapse-like drinking after a deprivation period in rats. We conclude that CRH/CRHR1 extra-HPA and HPA signaling may have opposing effects on stress-related alcohol consumption. CRHR1 does not have a role in basal alcohol intake or relapse-like drinking situations with a low stress load.......Corticotropin-releasing hormone (CRH) and its receptor, CRH receptor-1 (CRHR1), have a key role in alcoholism. Especially, post-dependent and stress-induced alcohol intake involve CRH/CRHR1 signaling within extra-hypothalamic structures, but a contribution of the hypothalamic-pituitary-adrenal (HPA...

  9. Human neutrophil peptide-1 promotes alcohol-induced hepatic fibrosis and hepatocyte apoptosis.

    Rie Ibusuki

    Full Text Available Neutrophil infiltration of the liver is a typical feature of alcoholic liver injury. Human neutrophil peptide (HNP-1 is an antimicrobial peptide secreted by neutrophils. The aim of this study was to determine if HNP-1 affects ethanol-induced liver injury and to examine the mechanism of liver injury induced by HNP-1.Transgenic (TG mice expressing HNP-1 under the control of a β-actin-based promoter were established. Ethanol was orally administered to HNP-1 TG or wild-type C57BL/6N (WT mice. SK-Hep1 hepatocellular carcinoma cells were used to investigate the effect of HNP-1 on hepatocytes in vitro.After 24 weeks of ethanol intake, hepatic fibrosis and hepatocyte apoptosis were significantly more severe in TG mice than in WT mice. Levels of CD14, TLR4, and IL-6 in liver tissues were higher in TG mice than in WT mice. Apoptosis was accompanied by higher protein levels of caspase-3, caspase-8, and cleaved PARP in liver tissue. In addition, phosphorylated ASK1, ASK1, phosphorylated JNK, JNK1, JNK2, Bax, Bak and Bim were all more abundant in TG mice than in WT mice. In contrast, the level of anti-apoptotic Bcl2 in the liver was significantly lower in TG mice than in WT mice. Analysis of microRNAs in liver tissue showed that miR-34a-5p expression was significantly higher in TG mice than in WT mice. Furthermore, in the presence of ethanol, HNP-1 increased the apoptosis with the decreased level of Bcl2 in a concentration-dependent manner in vitro.HNP-1 secreted by neutrophils may exacerbate alcohol-induced hepatic fibrosis and hepatocyte apoptosis with a decrease in Bcl2 expression and an increase in miR-34a-5p expression.

  10. Protective role of ginkgo Biloba extract against gamma radiation and alcohol induced liver damage in albino rats

    Fahmy, N. M.; Mohamed, E.T.; Mansour, H.H; Hafez, H.F.

    2007-01-01

    Ginkgo biloba extract (EGb 761) is a standardized extract of Ginkgo biloba leaves that promotes vasodilatation and improves blood flow through arteries, veins and capillaries and has antioxidant properties as a tree radical scavenger. This study was designed to evaluate the protective efficacy of EGb 761 against gamma radiation and/ or alcohol induced disorders in the liver of male albino rats. EGb 761 was given orally at a dose level of 100 mg/ kg body wt for 4 days, absolute alcohol was administered orally at a dose level of 1ml/ rat for 4 days and the dose of gamma radiation was 6.5 Gy. All animals were subjected to the following investigations: nitric oxide (NO), superoxide dismutase (SOD), malonaldehyde (MDA). reduced glutathion (GSH) and glutathione peroxidase (GSHPx) in the liver tissue. In irradiated and/ or alcoholic animal groups, there was a highly significant decrease in liver NO and GSH content and in the activities of GSHPx and SOD. On the other hand, significant increase in MDA content was observed. Treatment with EGb 761 before irradiation and/or alcohol causes significant increase in NO and GSH content and in the activities of GSHPx and SOD and significant decrease in MDA content compared to the irradiated and/ or alcoholic groups. Based on these observations, one could conclude that pre-treatment of rats with EGb 761 could partly protect liver from gamma rays and/ or absolute alcohol injurious and this protection may be induced, at least partly, through antioxidant mechanisms

  11. Peripherally Circulating Ghrelin Does Not Mediate Alcohol‐Induced Reward and Alcohol Intake in Rodents

    Jerlhag, Elisabet; Ivanoff, Lisa; Vater, Axel; Engel, Jörgen A.

    2014-01-01

    Background Development of alcohol dependence, a chronic and relapsing disease, largely depends on the effects of alcohol on the brain reward systems. By elucidating the mechanisms involved in alcohol use disorder, novel treatment strategies may be developed. Ghrelin, the endogenous ligand for the growth hormone secretagogue receptor 1A, acts as an important regulator of energy balance. Recently ghrelin and its receptor were shown to mediate alcohol reward and to control alcohol consumption in...

  12. Alcohol-induced defects in hepatic transcytosis may be explained by impaired dynein function.

    Groebner, Jennifer L; Fernandez, David J; Tuma, Dean J; Tuma, Pamela L

    2014-12-01

    Alcoholic liver disease has been clinically well described, but the molecular mechanisms leading to hepatotoxicity have not been fully elucidated. Previously, we determined that microtubules are hyperacetylated and more stable in ethanol-treated WIF-B cells, VL-17A cells, liver slices, and in livers from ethanol-fed rats. From our recent studies, we believe that these modifications can explain alcohol-induced defects in microtubule motor-dependent protein trafficking including nuclear translocation of a subset of transcription factors. Since cytoplasmic dynein/dynactin is known to mediate both microtubule-dependent translocation and basolateral to apical/canalicular transcytosis, we predicted that transcytosis is impaired in ethanol-treated hepatic cells. We monitored transcytosis of three classes of newly synthesized canalicular proteins in polarized, hepatic WIF-B cells, an emerging model system for the study of liver disease. As predicted, canalicular delivery of all proteins tested was impaired in ethanol-treated cells. Unlike in control cells, transcytosing proteins were observed in discrete sub-canalicular puncta en route to the canalicular surface that aligned along acetylated microtubules. We further determined that the stalled transcytosing proteins colocalized with dynein/dynactin in treated cells. No changes in vesicle association were observed for either dynein or dynactin in ethanol-treated cells, but significantly enhanced dynein binding to microtubules was observed. From these results, we propose that enhanced dynein binding to microtubules in ethanol-treated cells leads to decreased motor processivity resulting in vesicle stalling and in impaired canalicular delivery. Our studies also importantly indicate that modulating cellular acetylation levels with clinically tolerated deacetylase agonists may be a novel therapeutic strategy for treating alcoholic liver disease.

  13. Trauma- and Stress-Induced Response in Veterans with Alcohol Dependence and Comorbid Post-Traumatic Stress Disorder.

    Ralevski, Elizabeth; Southwick, Steven; Jackson, Eric; Jane, Jane Serrita; Russo, Melanie; Petrakis, Ismene

    2016-08-01

    Alcohol dependence (AD) and post-traumatic stress disorder (PTSD) commonly co-occur, and the co-occurrence is associated with worse prognosis than either disorder absent the other. Craving is an important construct related to relapse, but the relationship between PTSD symptoms, craving, and relapse is not well understood. Several studies have documented the relationship between stress and craving in individuals without comorbid PTSD, but the effect on those with comorbid PTSD is not well known. A small literature suggests that trauma imagery affects craving. This is the first study to explore the effects of trauma-induced and stress-induced scripts on alcohol craving, affect, cardiovascular, and cortisol responses in the laboratory. Veterans (n = 25) diagnosed with AD and PTSD who were participating in a randomized clinical treatment trial took part in this laboratory study. Baseline assessment included PTSD symptoms and drinking quantity and frequency over 3 months before study initiation. In the laboratory, participants were exposed to neutral, stressful, and trauma scripts randomly assigned. Main outcomes included craving, anxiety, mood states, salivary cortisol, and cardiovascular responses. Both stress and trauma scripts produced greater increases in craving, negative affect, and cardiovascular reactivity, compared to neutral scripts. Trauma scripts produced significantly stronger craving for alcohol and greater cardiovascular reactivity than stress scripts. Also, trauma-induced but not stress-induced craving was positively correlated with baseline levels of drinking. There were no changes in cortisol levels from pre- to postexposure of any scripts. The results highlight that trauma cues are more salient in inducing alcohol craving than stress cues and higher reactivity is related to more baseline drinking. This finding is consistent with clinical observations that show an association between PTSD symptoms and alcohol relapse. It also underscores the

  14. Moderate acute intake of de-alcoholized red wine, but not alcohol, is protective against radiation-induced DNA damage ex vivo -- results of a comparative in vivo intervention study in younger men.

    Greenrod, W; Stockley, C S; Burcham, P; Abbey, M; Fenech, M

    2005-12-11

    Moderate intake of wine is associated with reduced risk of cardiovascular disease and possibly cancer however it remains unclear whether the potential health benefits of wine intake are due to alcohol or the non-alcoholic fraction of wine. We therefore tested the hypothesis that the non-alcoholic fraction of wine protects against genome damage induced by oxidative stress in a crossover intervention study involving six young adult males aged 21-26 years. The participants adhered to a low plant phenolic compound diet for 48 h prior to consuming 300 mL of complete red wine, de-alcoholized red wine or ethanol on separate occasions 1 week apart. Blood samples were collected 0.5, 1.0 and 2.0 h after beverage consumption. Baseline and radiation-induced genome damage was measured using the cytokinesis-block micronucleus assay and total plasma catechin concentration was measured. Consumption of de-alcoholized red wine significantly decreased the gamma radiation-induced DNA damage at 1 and 2 h post-consumption by 20%. In contrast alcohol tended to increase radiation-induced genome damage and complete wine protected against radiation-induced genome damage relative to alcohol. The observed effects were only weakly correlated with the concentration of total plasma catechin (R=-0.23). These preliminary data suggest that only the non-alcoholic fraction of red wine protects DNA from oxidative damage but this effect cannot be explained solely by plasma catechin.

  15. Comparative effects of curcumin and its analog on alcohol- and polyunsaturated fatty acid-induced alterations in circulatory lipid profiles.

    Rukkumani, Rajagopalan; Aruna, Kode; Varma, Penumathsa Suresh; Rajasekaran, Kallikat Narayanan; Menon, Venugopal P

    2005-01-01

    Excessive alcohol intake induces hyperlipidemia. Studies suggest that natural principles and their analogs are known to possess anti-hyperlipidemic properties. In the present work we tested the effect of curcumin, an active principle of turmeric (Curcuma longa), and a curcumin analog on alcohol- and thermally oxidized polyunsaturated fatty acid (deltaPUFA)- induced hyperlipidemia. Male albino Wistar rats were used for the experimental study. Anti-hyperlipidemic activity of curcumin and curcumin analog was evaluated by analyzing the levels of cholesterol, triglycerides (TGs), phospholipids (PLs), and free fatty acids (FFAs). The results showed that the levels of cholesterol, TGs, PLs, and FFAs were increased significantly in alcohol-, deltaPUFA-, and alcohol + deltaPUFA-treated groups, which were brought down significantly on treatment with either of the curcuminoids. Curcumin analog treatment was found to be more effective than curcumin treatment. From the results obtained, we conclude that both curcumin and its analog effectively protect the system against alcohol- and deltaPUFA-induced hyperlipidemia and are possible candidates for the treatment of hyperlipidemia.

  16. Protective function of complement against alcohol-induced rat liver damage.

    Bykov, Igor L; Väkevä, Antti; Järveläinen, Harri A; Meri, Seppo; Lindros, Kai O

    2004-11-01

    The complement system can promote tissue damage or play a homeostatic role in the clearance and disposal of damaged tissue. We assessed the role of the terminal complement pathway in alcohol-induced liver damage in complement C6 (C6-/-) genetically deficient rats. C6-/- and corresponding C6+/+ rats were continuously exposed to ethanol by feeding ethanol-supplemented liquid diet for six weeks. Liver samples were analyzed for histopathology and complement component deposition by immunofluorescence microscopy. Prostaglandin E receptors and cytokine mRNA levels were analyzed by RT-PCR and plasma cytokines by ELISA. Deposition of complement components C1, C3, C8 and C9 was observed in C6+/+ rats, but not in C6-/- animals. The histopathological changes, the liver weight increase and the elevation of the plasma pro-/anti-inflammatory TNF-alpha/IL-10 ratio were, on the other hand, more marked in C6-/- rats. Furthermore, ethanol enhanced the hepatic mRNA expression of the prostaglandin E receptors EP2R and EP4R exclusively in the C6-/- rats. Our results indicate that a deficient terminal complement pathway predisposes to tissue injury and promotes a pro-inflammatory cytokine response. This suggests that an intact complement system has a protective function in the development of alcoholic liver damage.

  17. Chemically induced dynamic electron polarization. Pulse radiolysis of aqueous solutions of alcohols

    Trifunac, A.D.; Thurnauer, M.C.

    1975-01-01

    The radical pair model of chemically induced dynamic electron polarization (CIDEP) is experimentally verified. Aqueous solutions of alcohols were irradiated with 3 MeV electrons and observed with time resolved electron paramagnetic resonance (EPR) spectroscopy. Relative line intensities of the polarized EPR spectra of radicals from methanol and especially ethylene glycol, alone and in the presence of radicals from compounds containing halogens, illustrates the polarization dependence on the g-factor differences between the radical pair components. The observation of the relative polarization enhancement in the various lines of the multiline EPR spectra illustrates the polarization dependence on the hyperfine terms. Intrinsic enhancements are calculated and are shown to be proportional to the observed enhancement, showing that the radical pair model of CIDEP is qualitatively correct

  18. Reaction mechanism of hydroxymaleimide induced by γ-irradiation in alcohol solvents

    Nakagawa, Seiko

    2010-01-01

    Methanol and 2-propanol solutions of hydroxymaleimide were irradiated with γ-ray and mechanism of its γ-irradiation-induced reactions was investigated through final-product analyses using high performance liquid chromatography (HPLC) coupled with mass spectroscopy. An addition reaction of a solvent radical toward hydroxymaleimide was dominant among its oxygen-free γ-irradiation-induced reactions in its alcohol solutions while it is known that electron attachment toward hydroxyphthalimide or hydroxysuccinimide is dominant among their γ-irradiation-induced reactions. The radical adduct abstracts hydrogen from solvent molecule to re-produce a solvent radical. Therefore, the degradation efficiency of hydroxymaleimide was more than ten times larger than that of hydroxyphthalimide and hydroxysuccinimide. Dimer was also produced through electron attachment process in the solutions of hydroxymaleimide. In addition, it was found that the degradation efficiency increased with decrease in dose rate. An additional reaction of a solvent radical toward hydroxymaleimide competes with a radical-radical recombination. The latter was reduced, with the former leading to efficient degradation of hydroxymaleimide increased by irradiation at lower dose rate. On the contrary, the production yield of the adduct radical as well as the degradation efficiency of hydroxymaleimide was inhibited in the presence of oxygen.

  19. Reaction mechanism of hydroxymaleimide induced by γ-irradiation in alcohol solvents

    Nakagawa, Seiko

    2010-01-01

    Methanol and 2-propanol solutions of hydroxymaleimide were irradiated with γ-ray and mechanism of its γ-irradiation-induced reactions was investigated through final-product analyses using high performance liquid chromatography (HPLC) coupled with mass spectroscopy. An addition reaction of a solvent radical toward hydroxymaleimide was dominant among its oxygen-free γ-irradiation-induced reactions in its alcohol solutions while it is known that electron attachment toward hydroxyphthalimide or hydroxysuccinimide is dominant among their γ-irradiation-induced reactions. The radical adduct abstracts hydrogen from solvent molecule to re-produce a solvent radical. Therefore, the degradation efficiency of hydroxymaleimide was more than 10 times larger than that of hydroxyphthalimide and hydroxysuccinimide. Dimer was also produced through electron attachment process in the solutions of hydroxymaleimide. In addition, it was found that the degradation efficiency increased with decreasing the dose rate. An addition reaction of a solvent radical toward hydroxymaleimide competes with a radical-radical recombination. The latter was reduced and the former leading to efficient degradation of hydroxymaleimide increased by irradiation at lower dose rate. On the contrary, the production yield of the adduct radical as well as the degradation efficiency of hydroxymaleimide was inhibited in the presence of oxygen.

  20. Alcohol-induced blackout as a criminal defense or mitigating factor: an evidence-based review and admissibility as scientific evidence.

    Pressman, Mark R; Caudill, David S

    2013-07-01

    Alcohol-related amnesia--alcohol blackout--is a common claim of criminal defendants. The generally held belief is that during an alcohol blackout, other cognitive functioning is severely impaired or absent. The presentation of alcohol blackout as scientific evidence in court requires that the science meets legal reliability standards (Frye, FRE702/Daubert). To determine whether "alcohol blackout" meets these standards, an evidence-based analysis of published scientific studies was conducted. A total of 26 empirical studies were identified including nine in which an alcohol blackout was induced and directly observed. No objective or scientific method to verify the presence of an alcoholic blackout while it is occurring or to confirm its presence retrospectively was identified. Only short-term memory is impaired and other cognitive functions--planning, attention, and social skills--are not impaired. Alcoholic blackouts would not appear to meet standards for scientific evidence and should not be admissible. © 2013 American Academy of Forensic Sciences.

  1. Increased anxiety, voluntary alcohol consumption and ethanol-induced place preference in mice following chronic psychosocial stress.

    Bahi, Amine

    2013-07-01

    Stress exposure is known to be a risk factor for alcohol use and anxiety disorders. Comorbid chronic stress and alcohol dependence may lead to a complicated and potentially severe treatment profile. To gain an understanding of the interaction between chronic psychosocial stress and drug exposure, we studied the effects of concomitant chronic stress exposure on alcohol reward using two-bottle choice and ethanol-conditioned place preference (CPP). The study consisted of exposure of the chronic subordinate colony (CSC) mice "intruders" to an aggressive "resident" mouse for 19 consecutive days. Control mice were single housed (SHC). Ethanol consumption using two-bottle choice paradigm and ethanol CPP acquisition was assessed at the end of this time period. As expected, CSC exposure increased anxiety-like behavior and reduced weight gain as compared to SHC controls. Importantly, in the two-bottle choice procedure, CSC mice showed higher alcohol intake than SHC. When testing their response to ethanol-induced CPP, CSC mice achieved higher preference for the ethanol-paired chamber. In fact, CSC exposure increased ethanol-CPP acquisition. Taken together, these data demonstrate the long-term consequences of chronic psychosocial stress on alcohol intake in male mice, suggesting chronic stress as a risk factor for developing alcohol consumption and/or anxiety disorders.

  2. Heat-Killed Lactobacillus salivarius and Lactobacillus johnsonii Reduce Liver Injury Induced by Alcohol In Vitro and In Vivo.

    Chuang, Cheng-Hung; Tsai, Cheng-Chih; Lin, En-Shyh; Huang, Chin-Shiu; Lin, Yun-Yu; Lan, Chuan-Ching; Huang, Chun-Chih

    2016-10-31

    The aim of the present study was to determine whether Lactobacillus salivarius (LS) and Lactobacillus johnsonii (LJ) prevent alcoholic liver damage in HepG2 cells and rat models of acute alcohol exposure. In this study, heat-killed LS and LJ were screened from 50 Lactobacillus strains induced by 100 mM alcohol in HepG2 cells. The severity of alcoholic liver injury was determined by measuring the levels of aspartate transaminase (AST), alanine transaminase (ALT), gamma-glutamyl transferase (γ-GT), lipid peroxidation, triglyceride (TG) and total cholesterol. Our results indicated that heat-killed LS and LJ reduced AST, ALT, γ-GT and malondialdehyde (MDA) levels and outperformed other bacterial strains in cell line studies. We further evaluated these findings by administering these strains to rats. Only LS was able to reduce serum AST levels, which it did by 26.2%. In addition LS significantly inhibited serum TG levels by 39.2%. However, both strains were unable to inhibit ALT levels. In summary, we demonstrated that heat-killed LS and LJ possess hepatoprotective properties induced by alcohol both in vitro and in vivo.

  3. Heat-Killed Lactobacillus salivarius and Lactobacillus johnsonii Reduce Liver Injury Induced by Alcohol In Vitro and In Vivo

    Cheng-Hung Chuang

    2016-10-01

    Full Text Available The aim of the present study was to determine whether Lactobacillus salivarius (LS and Lactobacillus johnsonii (LJ prevent alcoholic liver damage in HepG2 cells and rat models of acute alcohol exposure. In this study, heat-killed LS and LJ were screened from 50 Lactobacillus strains induced by 100 mM alcohol in HepG2 cells. The severity of alcoholic liver injury was determined by measuring the levels of aspartate transaminase (AST, alanine transaminase (ALT, gamma-glutamyl transferase (γ-GT, lipid peroxidation, triglyceride (TG and total cholesterol. Our results indicated that heat-killed LS and LJ reduced AST, ALT, γ-GT and malondialdehyde (MDA levels and outperformed other bacterial strains in cell line studies. We further evaluated these findings by administering these strains to rats. Only LS was able to reduce serum AST levels, which it did by 26.2%. In addition LS significantly inhibited serum TG levels by 39.2%. However, both strains were unable to inhibit ALT levels. In summary, we demonstrated that heat-killed LS and LJ possess hepatoprotective properties induced by alcohol both in vitro and in vivo.

  4. Light/Dark Shifting Promotes Alcohol-Induced Colon Carcinogenesis: Possible Role of Intestinal Inflammatory Milieu and Microbiota

    Faraz Bishehsari

    2016-12-01

    Full Text Available Background: Colorectal cancer (CRC is associated with the modern lifestyle. Chronic alcohol consumption—a frequent habit of majority of modern societies—increases the risk of CRC. Our group showed that chronic alcohol consumption increases polyposis in a mouse mode of CRC. Here we assess the effect of circadian disruption—another modern life style habit—in promoting alcohol-associated CRC. Method: TS4Cre × adenomatous polyposis coli (APClox468 mice underwent (a an alcohol-containing diet while maintained on a normal 12 h light:12 h dark cycle; or (b an alcohol-containing diet in conjunction with circadian disruption by once-weekly 12 h phase reversals of the light:dark (LD cycle. Mice were sacrificed after eight weeks of full alcohol and/or LD shift to collect intestine samples. Tumor number, size, and histologic grades were compared between animal groups. Mast cell protease 2 (MCP2 and 6 (MCP6 histology score were analyzed and compared. Stool collected at baseline and after four weeks of experimental manipulations was used for microbiota analysis. Results: The combination of alcohol and LD shifting accelerated intestinal polyposis, with a significant increase in polyp size, and caused advanced neoplasia. Consistent with a pathogenic role of stromal tryptase-positive mast cells in colon carcinogenesis, the ratio of mMCP6 (stromal/mMCP2 (intraepithelial mast cells increased upon LD shifting. Baseline microbiota was similar between groups, and experimental manipulations resulted in a significant difference in the microbiota composition between groups. Conclusions: Circadian disruption by Light:dark shifting exacerbates alcohol-induced polyposis and CRC. Effect of circadian disruption could, at least partly, be mediated by promoting a pro-tumorigenic inflammatory milieu via changes in microbiota.

  5. Early Maternal Deprivation Enhances Voluntary Alcohol Intake Induced by Exposure to Stressful Events Later in Life

    Sara Peñasco

    2015-01-01

    Full Text Available In the present study, we aimed to assess the impact of early life stress, in the form of early maternal deprivation (MD, 24 h on postnatal day, pnd, 9, on voluntary alcohol intake in adolescent male and female Wistar rats. During adolescence, from pnd 28 to pnd 50, voluntary ethanol intake (20%, v/v was investigated using the two-bottle free choice paradigm. To better understand the relationship between stress and alcohol consumption, voluntary alcohol intake was also evaluated following additional stressful events later in life, that is, a week of alcohol cessation and a week of alcohol cessation combined with exposure to restraint stress. Female animals consumed more alcohol than males only after a second episode of alcohol cessation combined with restraint stress. MD did not affect baseline voluntary alcohol intake but increased voluntary alcohol intake after stress exposure, indicating that MD may render animals more vulnerable to the effects of stress on alcohol intake. During adolescence, when animals had free access to alcohol, MD animals showed lower body weight gain but a higher growth rate than control animals. Moreover, the higher growth rate was accompanied by a decrease in food intake, suggesting an altered metabolic regulation in MD animals that may interact with alcohol intake.

  6. Understanding and Confronting Alcohol-Induced Risky Behavior among College Students

    Dornier, Lucien J.; Fauquier, Katharine J.; Field, April R.; Budden, Michael C.

    2010-01-01

    Confronting alcohol abuse is a challenge for most higher education institutions. Each year, students are admitted to hospitals for issues arising from the misuse of alcohol. The deaths of some engaged in alcohol related activities is especially worrisome. Factors such as age and financial standing could impact the likelihood of abuse. So-called…

  7. SIRT1 exhibits antioxidative effects in HT22 cells induced by tert-butyl alcohol.

    Ma, Junxiang; Song, Dongmei; Zhang, Yuanyuan; Chen, Li; Zhang, Shixuan; Jia, Jiaxin; Chen, Tian; Guo, Caixia; Tian, Lin; Gao, Ai; Niu, Piye

    2018-02-01

    Tertiary butyl alcohol (TBA) is a principal metabolite of methyl tertiary-butyl ether (MTBE), a common pollutant worldwide in the ground or underground water, which is found to produce nervous system damage. Nevertheless, few data regarding the effects of TBA has been reported. Studies indicated that oxidative stress plays a pivotal role in MTBE neurotoxic mechanism. Sirtuin 1 (SIRT1) has been reported to exert a neuroprotective effect on various neurologic diseases via resistance to oxidative stress by deacetylating its substrates. In this study, we examined levels of oxidative stress after exposure to TBA for 6 h in HT22 cells and HT22 cells with SIRT1 silencing (transfected with SIRT1 siRNA) or high expression (preconditioned with agonists SRT1720). We found that TBA activated oxidative stress by increasing generation of intracellular reactive oxygen species (ROS), malondialdehyde (MDA) and Oxidized glutathione (GSSG), and decreasing contents of superoxide dismutase (SOD) and glutathione reductase (GSH). In additional, levels of TBA-induced oxidative stress were aggravated when SIRT1 silenced but alleviated when SIRT1 enhanced. Our study indicated that SIRT1 mitigated oxidative stress induced by TBA. © 2017 Wiley Periodicals, Inc.

  8. Dietary agents in the prevention of alcohol-induced hepatotoxicty: preclinical observations.

    Shivashankara, Arnadi Ramachandrayya; Azmidah, Aysha; Haniadka, Raghavendra; Rai, Manoj Ponadka; Arora, Rajesh; Baliga, Manjeshwar Shrinath

    2012-02-01

    Long term alcohol consumption is one of the important causes for liver failure and death. To complicate the existing problem there are no dependable hepatoprotective drugs and a large number of patients prefer using complementary and alternative medicines for treating and managing hepatic complications. Almost 25 centuries ago, Hippocrates, the father of medicine, proclaimed "Let food be thy medicine and medicine be thy food." Exploring the association between diet and health continues even today. Preclinical studies carried out in the recent past have shown that the commonly used dietary agents like Allium sativum (garlic), Camellia sinensis (tea), Curcuma longa (turmeric), Emblica officinalis (Indian gooseberry), Ferula asafoetida (asafoetida), Garcinia cambogia (Malabar tamarind), Glycine max (soyabean), Murraya koenigii (curry leaves), Piper betle (beetle leaf), Prunus armeniaca (apricot), Ocimum gratissimum (wild basil), Theobroma cacao (cocoa), Trigonella foenum-graecum (fenugreek) and Vitis vinifera (grapes) protect against ethanol-induced hepatotoxicity. Mechanistic studies have shown that the beneficial effects of these phytochemicals in preventing the ethanol-induced hepatotoxicity are mediated by the antioxidant, free radical scavenging, anti-inflammatory and anti-fibrotic effects. The present review for the first time collates the hepatoprotective effects of these agents and also emphasizes on aspects that need future research to establish their utility in humans.

  9. Protective Effects of Ethanolic Extracts from Artichoke, an Edible Herbal Medicine, against Acute Alcohol-Induced Liver Injury in Mice

    Tang, Xuchong; Wei, Ruofan; Deng, Aihua; Lei, Tingping

    2017-01-01

    Oxidative stress and inflammation are well-documented pathological factors in alcoholic liver disease (ALD). Artichoke (Cynara scolymus L.) is a healthy food and folk medicine with anti-oxidative and anti-inflammatory properties. This study aimed to evaluate the preventive effects of ethanolic extract from artichoke against acute alcohol-induced liver injury in mice. Male Institute of Cancer Research mice were treated with an ethanolic extract of artichoke (0.4, 0.8, and 1.6 g/kg body weight)...

  10. Is nutrient intake a gender-specific cause for enhanced susceptibility to alcohol-induced liver disease in women?

    Wagnerberger, S.; Schafer, C.; Schwarz, E.

    2008-01-01

    Aim: Women have a higher susceptibility to alcohol-induced liver disease (ALD) than men. Gender-related differences in food preference were described in previous studies for several populations, but not in alcohol abusers. As certain micronutrients are reported to take influence on the development...... of ALD in animal experiments, the hypothesis of the present retrospective cross-sectional study was that gender-dependent (micro-) nutrient intake in patients with ALD may cause the higher susceptibility of women to this disease. Methods: In 210 patients (male: 158, female: 52) with different stages...

  11. Alcoholism and Alcohol Abuse

    ... their drinking causes distress and harm. It includes alcoholism and alcohol abuse. Alcoholism, or alcohol dependence, is a disease that causes ... the liver, brain, and other organs. Drinking during pregnancy can harm your baby. Alcohol also increases the ...

  12. Negative mood-induced alcohol-seeking is greater in young adults who report depression symptoms, drinking to cope, and subjective reactivity.

    Hogarth, Lee; Hardy, Lorna; Mathew, Amanda R; Hitsman, Brian

    2018-04-01

    Acute negative mood powerfully motivates alcohol-seeking behavior, but it remains unclear whether sensitivity to this effect is greater in drinkers who report depression symptoms, drinking to cope, and subjective reactivity. To examine these questions, 128 young adult alcohol drinkers (ages 18-25) completed questionnaires of alcohol use disorder symptoms, depression symptoms, and drinking to cope with negative affect. Baseline alcohol choice was measured by preference to enlarge alcohol versus food thumbnail images in two-alternative forced-choice trials. Negative mood was then induced by depressive statements and music, before alcohol choice was tested. Subjective reactivity was indexed by increased sadness pre- to post-mood induction. Baseline alcohol choice correlated with alcohol dependence symptoms (p = .001), and drinking coping motives (ps ≤ .01). Mood induction increased alcohol choice and subjective sadness overall (ps choice was associated with depression symptoms (p = .007), drinking to cope (ps ≤ .03), and subjective reactivity (p = .007). The relationship between mood-induced alcohol choice and drinking to cope remained significant after covarying for other drinking motives. Furthermore, the three predictors (depression, drinking to cope, and subjective reactivity) accounted for unique variance in mood-induced alcohol choice (ps ≥ .03), and collectively accounted for 18% of the variance (p choice task as sensitive to the relative value of alcohol and acute negative mood. The findings also accord with the core prediction of negative reinforcement theory that sensitivity to the motivational impact of negative mood on alcohol-seeking behavior may be an important mechanism that links depression and alcohol dependence. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  13. Effect of Trace Elements in Alcohol Beverages on the Type of Radiation-induced Cell Death

    Sohn, Jong Gi

    2010-01-01

    Developments of radioprotective agents are important issues for minimizing the troubles and the effective treatments in radiotherapy. But few agents are useful in clinical and practical fields. It was shown that trace elements in alcohol beverages might have radioprotective effect. In this study, the types of cell death of lymphocytes according to the commercial alcohol beverage was investigated. Normal healthy volunteers ingested distilled water, beer or soju containing 8.15 mg·dl -1 ethyl ahcohol, respectively. After 2 hours, their blood were sampled with their consents. Fraction of lymphocytes was isolated by density gradient method with Histopaque-1077 (Sigma) and irradiated with dose from 0.5 to 5 Gy. After 60 hour incubation, the cells were harvested and analysed by flow cytometry. Cell viability was decreased by dose dependent manner. Cell viability of beer group was reduced about 15% compared with control group. Apoptosis in soju group was reduced about 20% compared with control group. Apoptosis of beer and control groups are similar. Necrosis of soju group significantly increased about 35% compared with control group. Early apoptosis of beer group was increased compared with control group. Early apoptosis of soju group was decreased about 25% compared with control group. Late apoptosis of beer and control group was increased by dose dependent manner. Late apoptosis of soju group was increased about 20-30% compared with control group. Late apoptosis of soju was increased and the radioprotective effect of soju was minimal because late apoptosis induced the cell necrosis. In case of soju trace elements, total cell apoptosis was decreased about 20% and early cell apoptosis was remarkably low. In this case, mitotic cells death may be dominant mechanism. Therefore, trace elements in soju may not be effective radioprotective agents

  14. Alcohol-induced retrograde memory impairment in rats: prevention by caffeine.

    Spinetta, Michael J; Woodlee, Martin T; Feinberg, Leila M; Stroud, Chris; Schallert, Kellan; Cormack, Lawrence K; Schallert, Timothy

    2008-12-01

    Ethanol and caffeine are two of the most widely consumed drugs in the world, often used in the same setting. Animal models may help to understand the conditions under which incidental memories formed just before ethanol intoxication might be lost or become difficult to retrieve. Ethanol-induced retrograde amnesia was investigated using a new odor-recognition test. Rats thoroughly explored a wood bead taken from the cage of another rat, and habituated to this novel odor (N1) over three trials. Immediately following habituation, rats received saline, 25 mg/kg pentylenetetrazol (a seizure-producing agent known to cause retrograde amnesia) to validate the test, 1.0 g/kg ethanol, or 3.0 g/kg ethanol. The next day, they were presented again with N1 and also a bead from a new rat's cage (N2). Rats receiving saline or the lower dose of ethanol showed overnight memory for N1, indicated by preferential exploration of N2 over N1. Rats receiving pentylenetetrazol or the higher dose of ethanol appeared not to remember N1, in that they showed equal exploration of N1 and N2. Caffeine (5 mg/kg), delivered either 1 h after the higher dose of ethanol or 20 min prior to habituation to N1, negated ethanol-induced impairment of memory for N1. A combination of a phosphodiesterase-5 inhibitor and an adenosine A(2A) antagonist, mimicking two major mechanisms of action of caffeine, likewise prevented the memory impairment, though either drug alone had no such effect. Binge alcohol can induce retrograde, caffeine-reversible disruption of social odor memory storage or recall.

  15. Reversal of alcohol induced testicular hyperlipidemia by supplementation of ascorbic acid and its comparison with abstention in male guinea pigs.

    Radhakrishnakartha, Harikrishnan; Appu, Abhilash Puthuvelvippel; Madambath, Indira

    2014-02-01

    Chronic ethanol exposure causes hyperlipidemia. The present study was designed to investigate the impact of ascorbic acid supplementation on ethanol induced hyperlipidemia in testis and to compare it with that of abstinence from taking alcohol. Thirty-six male guinea pigs were divided into two groups and were maintained for 90 days as follows (1) control (C) (2) ethanol treated group (E) (4 g/kg body wt/day). Ethanol was administered for 90 days and on 90th day, alanine amino transaminase (ALT), aspartate amino transaminase (AST) and γ-glutamyltransferase (GGT) in serum was assayed. The animals in the ethanol group were further divided into an ascorbic acid supplemented group (25 mg/100 g body wt/day) (E+AA) and an ethanol abstention group (EAG) and those in the control group were divided into a control group and a control+ascorbic acid group (C+AA). There was significant increase in levels of testicular cholesterol, free fatty acid, phospholipids and triglycerides in the ethanol group. There was also a significant increase in the activity of HMG CoA reductase and decrease in activity of testicular glucose-6-phosphate dehydrogenase (G6PDH) and malic enzyme in ethanol-ingested animals that further led to decreased levels of serum testosterone. Alcohol administration also enhanced the activity of testicular alcohol dehydrogenase (ADH). Ascorbic acid supplementation and abstention altered all these parameters induced by chronic alcohol administration. Histological studies were also in line with the above results. Ascorbic acid was able to reinstate the cholesterol homeostasis in testis which could have further restored the testicular steroidogenesis. The present study demonstrated that ascorbic acid is effective in reducing the hyperlipidemia induced by chronic alcohol administration and produced a better recovery than abstention.

  16. Protective Effects of Ethanolic Extracts from Artichoke, an Edible Herbal Medicine, against Acute Alcohol-Induced Liver Injury in Mice.

    Tang, Xuchong; Wei, Ruofan; Deng, Aihua; Lei, Tingping

    2017-09-11

    Oxidative stress and inflammation are well-documented pathological factors in alcoholic liver disease (ALD). Artichoke ( Cynara scolymus L.) is a healthy food and folk medicine with anti-oxidative and anti-inflammatory properties. This study aimed to evaluate the preventive effects of ethanolic extract from artichoke against acute alcohol-induced liver injury in mice. Male Institute of Cancer Research mice were treated with an ethanolic extract of artichoke (0.4, 0.8, and 1.6 g/kg body weight) by gavage once daily. Up to 40% alcohol (12 mL/kg body weight) was administered orally 1 h after artichoke treatment. All mice were fed for 10 consecutive days. Results showed that artichoke extract significantly prevented elevated levels of aspartate aminotransferase, alanine aminotransferase, triglyceride, total cholesterol, and malondialdehyde. Meanwhile, the decreased levels of superoxide dismutase and glutathione were elevated by artichoke administration. Histopathological examination showed that artichoke attenuated degeneration, inflammatory infiltration and necrosis of hepatocytes. Immunohistochemical analysis revealed that expression levels of toll-like receptor (TLR) 4 and nuclear factor-kappa B (NF-κB) in liver tissues were significantly suppressed by artichoke treatment. Results obtained demonstrated that artichoke extract exhibited significant preventive protective effect against acute alcohol-induced liver injury. This finding is mainly attributed to its ability to attenuate oxidative stress and suppress the TLR4/NF-κB inflammatory pathway. To the best of our knowledge, the underlying mechanisms of artichoke on acute ALD have been rarely reported.

  17. Binge-pattern alcohol exposure during puberty induces long-term changes in HPA axis reactivity.

    Magdalena M Przybycien-Szymanska

    2011-04-01

    Full Text Available Adolescence is a dynamic and important period of brain development however, little is known about the long-term neurobiological consequences of alcohol consumption during puberty. Our previous studies showed that binge-pattern ethanol (EtOH treatment during pubertal development negatively dysregulated the responsiveness of the hypothalamo-pituitary-adrenal (HPA axis, as manifested by alterations in corticotrophin-releasing hormone (CRH, arginine vasopressin (AVP, and corticosterone (CORT during this time period. Thus, the primary goal of this study was to determine whether these observed changes in important central regulators of the stress response were permanent or transient. In this study, juvenile male Wistar rats were treated with a binge-pattern EtOH treatment paradigm or saline alone for 8 days. The animals were left undisturbed until adulthood when they received a second round of treatments consisting of saline alone, a single dose of EtOH, or a second binge-pattern treatment paradigm. The results showed that pubertal binge-pattern EtOH exposure induced striking long-lasting alterations of many HPA axis parameters. Overall, our data provide strong evidence that binge-pattern EtOH exposure during pubertal maturation has long-term detrimental effects for the healthy development of the HPA axis.

  18. Rat model hindlimb ischemia induced via embolization with polyvinyl alcohol and N butyl cyanoacrylate

    Shin, Cheong Il; Kim, Hyo Cheol; Song, Yong Sub; Cho, Hye Rim; Lee, Kyoung Bun; Jae, Hwan June; Chung, Jin Wook [Seoul National University Hospital, Seoul (Korea, Republic of)

    2013-12-15

    To investigate the feasibility of a rat model on hindlimb ischemia induced by embolization from the administration of polyvinyl alcohol (PVA) particles or N-butyl cyanoacrylate (NBCA). Unilateral hindlimb ischemia was induced by embolization with NBCA (n = 4), PVA (n = 4) or surgical excision (n = 4) in a total of 12 Sprague-Dawley rats. On days 0, 7 and 14, the time-of-flight magnetic resonance angiography (TOF-MRA) and enhanced MRI were obtained as scheduled by using a 3T-MR scanner. The clinical ischemic index, volume change and degree of muscle necrosis observed on the enhanced MRI in the ischemic hindlimb were being compared among three groups using the analysis of variance. Vascular patency on TOF-MRA was evaluated and correlated with angiographic findings when using an inter-rater agreement test. There was a technical success rate of 100% for both the embolization and surgery groups. The clinical ischemic index did not significantly differ. On day 7, the ratios of the muscular infarctions were 0.436, 0.173 and 0 at thigh levels and 0.503, 0.337 and 0 at calf levels for the NBCA, PVA and surgery groups, respectively. In addition, the embolization group presented increased volume and then decreased volume on days 7 and 14, respectively. The surgery group presented a gradual volume decrease. Good correlation was shown between the TOF-MRA and angiographic findings (kappa value of 0.795). The examined hindlimb ischemia model using embolization with NBCA and PVA particles in rats is a feasible model for further research, and muscle necrosis was evident as compared with the surgical model.

  19. Intestinal flora imbalance promotes alcohol-induced liver fibrosis by the TGFβ/smad signaling pathway in mice.

    Zhang, Dong; Hao, Xiuxian; Xu, Lili; Cui, Jing; Xue, Li; Tian, Zibin

    2017-10-01

    Intestinal flora performs a crucial role in human health and its imbalance may cause numerous pathological changes. The liver can also affect the intestinal function through bile secretion via the enterohepatic cycle. The pathophysiological association between the gut and the liver is described as the gut-liver axis. The present study investigated the role of intestinal flora in alcohol-induced liver fibrosis. A total of 36 C57 mice were randomly and equally divided into 3 different dietary regimes: Group I (alcohol injury; received alcohol); group II (alcohol injury with flora imbalance; received alcohol plus lincomycin hydrochloride) and group III (alcohol injury with corrected flora imbalance; received alcohol, lincomycin hydrochloride and extra probiotics). The present study then investigated several indicators of liver damage. Alkaline phosphatase (ALP) levels, aspartate aminotransferase (AST) levels and alanine aminotransferase (ALT) levels in mice serum were studied. Masson staining and Annexin V-fluorescein isothiocyanate/propidium iodide double staining was also performed, and the expression of mothers against decapentaplegic homolog (smad) 3 and smad4 proteins in hepatic stellate cells (HSCs) of the mice was examined using western blot analysis. The levels of serum ALP, AST and ALT were the highest in group II mice, and all 3 levels decreased in group III mice compared with those from group II. The degree of liver fibrosis was aggravated in group II mice compared with group I mice. The apoptosis of HSCs was significantly inhibited in group II mice, but was increased in group III mice. The HSCs in group II mice exhibited higher expression of smad3 and smad4, whilst group III mice (with corrected intestinal flora imbalance) exhibited downregulated expression of smad3 and smad4. The present data indicates that the intestinal flora perform a significant role in maintaining liver homeostasis. Furthermore, an imbalance of intestinal flora can exacerbate alcohol-induced

  20. Effect of juice and fermented vinegar from Hovenia dulcis peduncles on chronically alcohol-induced liver damage in mice.

    Xiang, Jinle; Zhu, Wenxue; Li, Zhixi; Ling, Shengbao

    2012-06-01

    The protective effects of juice and fermented vinegar from Hovenia dulcis peduncles on chronically ethanol-induced biochemical changes in male mice were investigated. Administration of ethanol (50%, v/v, 10 mL kg⁻¹) to mice for 6 weeks induced liver damage with a significant increase (P vinegar from Hovenia dulcis peduncles (10 mL kg⁻¹ bw) along with alcohol significantly (P vinegar from Hovenia dulcis peduncles showed better profiles of the antioxidant systems with relatively higher glutathione (GSH) content, total superoxide dismutase (T-SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities. All these results were accompanied by histological observations in liver. The results demonstrate that both of the juice and fermented vinegar from Hovenia dulcis peduncles have beneficial effects in reducing the adverse effect of alcohol.

  1. Tolerance to disulfiram induced by chronic alcohol intake in the rat.

    Tampier, Lutske; Quintanilla, María Elena; Israel, Yedy

    2008-06-01

    Disulfiram, an inhibitor of aldehyde dehydrogenase used in the treatment of alcoholism, is an effective medication when its intake is supervised by a third person. However, its therapeutic efficacy varies widely, in part due to the fact that disulfiram is a pro-drug that requires its transformation into an active form and because it shows a wide range of secondary effects which often prevent the use of doses that ensure full therapeutic effectiveness. In this preclinical study in rats we report the development of tolerance to disulfiram induced by the chronic ingestion of ethanol, an additional source of variation for the actions of disulfiram with possible therapeutic significance, We also addresses the likely mechanism of this effect. Wistar-derived rats bred for generations as high ethanol drinkers (UChB) were trained for either 3 days (Group A) or 30 days (Group B) to choose between ethanol (10% v/v) or water, which were freely available from 2 bottles on a 24-hour basis. Subsequently, animals in both groups were administered disulfiram or cyanamide (another inhibitor of aldehyde dehydrogenase) and ethanol intake in this free choice paradigm was determined. Animals were also administered a standard dose of 1 g ethanol/kg (i.p) and arterial blood acetaldehyde was measured. Disulfiram (12.5 and 25 mg/kg) and cyanamide (10 mg/kg) markedly inhibited ethanol intake (up to 60 to 70%) in animals that had ethanol access for only 3 days (Group A). However both drugs were inactive in inhibiting ethanol intake in animals that had consumed ethanol for 30 days (Group B). Following the injection of 1 g ethanol/kg, arterial blood acetaldehyde levels reached levels of 150 and 300 microM for disulfiram and cyanamide respectively, values which were virtually identical regardless of the length of prior ethanol intake of the animals. Chronic ethanol intake in high-drinker rats leads to marked tolerance to the aversive effects of disulfiram and cyanamide on ethanol intake despite

  2. Schisandra sphenanthera extract (Wuzhi Tablet protects against chronic-binge and acute alcohol-induced liver injury by regulating the NRF2-ARE pathway in mice

    Xuezhen Zeng

    2017-09-01

    Full Text Available Alcohol abuse leads to alcoholic liver disease and no effective therapy is currently available. Wuzhi Tablet (WZ, a preparation of extract from Schisandra sphenanthera that is a traditional hepato-protective herb, exerted a significant protective effect against acetaminophen-induced liver injury in our recent studies, but whether WZ can alleviate alcohol-induced toxicity remains unclear. This study aimed to investigate the contribution of WZ to alcohol-induced liver injury by using chronic-binge and acute models of alcohol feeding. The activities of ALT and AST in serum were assessed as well as the level of GSH and the activity of SOD in the liver. The expression of CYP2E1 and proteins in the NRF2-ARE signaling pathway including NRF2, GCLC, GCLM, HO-1 were measured, and the effect of WZ on NRF2 transcriptional activity was determined. We found that both models resulted in liver steatosis accompanied by increased transaminase activities, but that liver injury was significantly attenuated by WZ. WZ administration also inhibited CYP2E1 expression induced by alcohol, and elevated the level of GSH and the activity of SOD in the liver. Moreover, the NRF2-ARE signaling pathway was activated by WZ and the target genes were all upregulated. Furthermore, WZ significantly activated NRF2 transcriptional activity. Collectively, our study demonstrates that WZ protected against alcohol-induced liver injury by reducing oxidative stress and improving antioxidant defense, possibly by activating the NRF2-ARE pathway.

  3. Moderate alcohol consumption aggravates high fat-diet induced steatohepatitis in rats

    Background: Nonalcoholic steatohepatitis (NASH) develops in the absence of chronic and excessive alcohol consumption. However, it remains unknown whether moderate alcohol consumption aggravates liver inflammation in pre-existing NASH condition. Methods: Sprague-Dawley rats were first fed ad libitum...

  4. Increased Sensitivity to Binge Alcohol-Induced Gut Leakiness and Inflammatory Liver Disease in HIV Transgenic Rats.

    Atrayee Banerjee

    Full Text Available The mechanisms of alcohol-mediated advanced liver injury in HIV-infected individuals are poorly understood. Thus, this study was aimed to investigate the effect of binge alcohol on the inflammatory liver disease in HIV transgenic rats as a model for simulating human conditions. Female wild-type (WT or HIV transgenic rats were treated with three consecutive doses of binge ethanol (EtOH (3.5 g/kg/dose oral gavages at 12-h intervals or dextrose (Control. Blood and liver tissues were collected at 1 or 6-h following the last dose of ethanol or dextrose for the measurements of serum endotoxin and liver pathology, respectively. Compared to the WT, the HIV rats showed increased sensitivity to alcohol-mediated gut leakiness, hepatic steatosis and inflammation, as evidenced with the significantly elevated levels of serum endotoxin, hepatic triglycerides, histological fat accumulation and F4/80 staining. Real-time PCR analysis revealed that hepatic levels of toll-like receptor-4 (TLR4, leptin and the downstream target monocyte chemoattractant protein-1 (MCP-1 were significantly up-regulated in the HIV-EtOH rats, compared to all other groups. Subsequent experiments with primary cultured cells showed that both hepatocytes and hepatic Kupffer cells were the sources of the elevated MCP-1 in HIV-EtOH rats. Further, TLR4 and MCP-1 were found to be upregulated by leptin. Collectively, these results show that HIV rats, similar to HIV-infected people being treated with the highly active anti-retroviral therapy (HAART, are more susceptible to binge alcohol-induced gut leakiness and inflammatory liver disease than the corresponding WT, possibly due to additive or synergistic interaction between binge alcohol exposure and HIV infection. Based on these results, HIV transgenic rats can be used as a surrogate model to study the molecular mechanisms of many disease states caused by heavy alcohol intake in HIV-infected people on HAART.

  5. Opposite effects of alcohol in regulating stress-induced changes in body weight between the two mouse lines with enhanced or low opioid system activity.

    Sacharczuk, Mariusz; Sadowski, Bogdan; Jaszczak, Kazimierz; Lipkowski, Andrzej W; Swiergiel, Artur H

    2010-04-19

    Considering the involvement of the opioid system in alcoholism, depression and metabolism - known risk factors in human obesity, we studied the effects of chronic mild stress (CMS) and alcohol intake on body weight in two mouse lines selected for high (HA-high analgesia) or low (LA-low analgesia) swim stress-induced analgesia. In comparison to LA mice, HA mice exhibit an upregulation of opioid receptor system function, different depression-like behavior and reduced energy expenditure in stress. LA animals showed enhanced basal and CMS-induced alcohol drinking versus HA. Now we report different effects of alcohol under no stress (control) and CMS conditions on food intake and body weight between the lines. CMS in animals with no access to alcohol increased body weight in both HA and LA mice, with no effect of CMS on food intake in either line and without differences between the lines. In LA mice alcohol reduced body weight under both conditions although significantly more under the control than CMS conditions. In contrast, in HA mice alcohol increased body weight more under the CMS than under control conditions. The results suggest that opioid system may modulate effects of alcohol on stress -induced changes in body weight. (c) 2010 Elsevier Inc. All rights reserved.

  6. IgA against gut-derived endotoxins: does it contribute to suppression of hepatic inflammation in alcohol-induced liver disease?

    Parlesak, Alexandr; Schäfer, C.; Bode, C.

    2002-01-01

    Endotoxins of intestinal origin are supposed to play an important role in the development of alcoholic hepatitis in man. To estimate the role of immunoglobulin response to gut-derived endotoxin in the development of alcohol-induced liver disease, serum levels of IgA and IgG against fecal endotoxin......, endotoxin, and acute-phase proteins were measured in patients with different stages of alcoholic liver disease and in healthy controls. Antibodies of type IgA, but not IgG, against fecal endotoxins were significantly increased in patients with alcohol-induced liver disease. IgA antibodies against fecal...... endotoxin were found to be closely correlated with the plasma concentrations of alanine aminotransferase, gamma-glutamyl transferase, and C-reactive protein in patients with alcoholic liver disease. In conclusion, as IgA located in body tissue was shown to suppress the inflammatory process, enhanced...

  7. On the adsorption-induced fatigue of structural steels in the presence of alcohols

    Loboiko, V.I.; Karpenko, G.V.; Vasilenko, I.I.

    1976-01-01

    The purpose of the work was to study he effect of anhydrous alcohols on the cyclic fatigue of steels in the absence of contact of the alcohol with atmospheric moisture during the testing process. A vacuum was created in the operating space and then the vacuum annealing was carried out in a bath with the sample and through metal vacuum connection the bath was filled with anhydrous alcohol. Studies were made on several construction steels (20Kh, 40Kh, 50Kh, and ShKh15); steels 40Kh, 50Kh, and ShKh15 were quenched from 840-860 0 C in oil and then tempered at 200 0 C (2 h), steel 20Kh was studied in the as-received state. It was shown that with increase in the carbon content of steel with a martensite structure, the decrease in strength in the presence of anhydrous alcohol was greater than in dry air. Experiments showed that anhydrous alcohol causes an adsorption decrease in the strength both of samples with preliminarily formed cracks and V-shaped stress concentrators and of smooth samples. The greatest adsorption effect of alcohols in our case, as in static fatigue, was observed in samples with cracks. A dependence was shown between the length of the carbon chain and the fatigue limit. This dependence indicates the monotone nature of the decrease in the fatigue limit with transfer from methyl to butyl and then to octyl alcohol

  8. Metronidazole-Induced Encephalopathy in Alcoholic Liver Disease: A Diagnostic and Therapeutic Challenge.

    Sonthalia, Nikhil; Pawar, Sunil V; Mohite, Ashok R; Jain, Samit S; Surude, Ravindra G; Rathi, Pravin M; Contractor, Qais

    2016-10-01

    Acute encephalopathy in a patient with alcoholic liver disease (ALD) is a commonly encountered emergency situation occurring most frequently due to liver failure precipitated by varying etiologies. Acute reversible cerebellar ataxia with confusion secondary to prolonged metronidazole use has been reported rarely as a cause of encephalopathy in patients with ALD. We describe a decompensated ALD patient with recurrent pyogenic cholangitis associated with hepatolithiasis who presented to the emergency department with sudden-onset cerebellar ataxia with dysarthria and mental confusion after prolonged use of metronidazole. Magnetic resonance imaging (MRI) of the brain was suggestive of bilateral dentate nuclei hyper intensities on T2 and fluid-attenuated inversion recovery sections seen classically in metronidazole-induced encephalopathy (MIE). Decompensated liver cirrhosis resulted in decreased hepatic clearance and increased cerebrospinal fluid concentration of metronidazole leading to toxicity at a relatively low total cumulative dose of 22 g. Both the clinical symptoms and MRI brain changes were reversed at 7 days and 6 weeks, respectively, after discontinuation of metronidazole. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: A patient with ALD presenting with encephalopathy creates a diagnostic dilemma for the emergency physician regarding whether to continue metronidazole and treat for hepatic encephalopathy or to suspect for MIE and withhold the drug. Failure to timely discontinue metronidazole may worsen the associated hepatic encephalopathy in these patients. Liver cirrhosis patients have higher mean concentration of metronidazole and its metabolite in the blood, making it necessary to keep the cumulative dose of metronidazole to < 20 g in them. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Saturation of retinol-binding protein correlates closely to the severity of alcohol-induced liver disease

    Wagnerberger, S.; Schäfer, C.; Bode, C.

    2006-01-01

    Impaired metabolism of retinol has been shown to occur in alcohol-induced liver disease (ALD). The purpose of the present study was to investigate the saturation of retinol-binding protein (RBP) in 6 patients with different stages of ALD. Hospitalized alcohol consumers (n=118) with different stages...... chromatography and enzyme-linked immunosorbent assay methods, respectively. No differences were noted in daily retinol intake, but subjects with ALD had significantly lower concentrations of retinol in plasma (ALD1: 1.81+/-0.17 micromol/l [mean+/-S.E.M.]; ALD2: 1.95+/-0.24 micromol/l; ALD3: 0.67+/-0.13 micromol......: 43.5+/-6.2%; ALD3: 29.0+/-5.1%). The present study indicates that plasma concentrations of retinol and RBP per se do not correlate to severity of ALD, but rather that the retinol/RBP ratio links to the severity of alcohol-induced liver damage. From these results, a reduced availability of retinol...

  10. Alcohol-induced changes in the brain as assessed by MRI and CT

    Geibprasert, Sasikhan [University of Toronto, Hospital for Sick Children, Division of Neuroradiology, Department of Diagnostic Imaging, Toronto, ON (Canada); Gallucci, Massimo [University Hospital ' ' S. Salvatore' ' , Division of Neuroradiology, Department of Diagnostic Imaging, L' Aquila (Italy); Krings, Timo [University of Toronto, Toronto Western Hospital, Division of Neuroradiology, Department of Medical Imaging, Toronto, ON (Canada)

    2010-06-15

    This review provides an overview of structural magnetic resonance imaging and computed tomography findings of direct and indirect alcohol-related toxic effects on the brain. In addition to ethanol-related changes to the brain, this article will also describe imaging findings in the acute setting of methanol and ethylene glycol poisoning. Alcohol will lead to brain atrophy, osmotic myelinolysis, Marchiafava-Bignami disease and, especially when related to malnutrition, may also cause Wernicke encephalopathy. Brain atrophy can be reversible if alcohol abuse is stopped. If not treated, Wernicke encephalopathy can lead to coma and death and an early diagnosis is important for immediate initiation of thiamine substitution. As clinical symptoms are often unspecific, the radiologist plays an important role in the detection of alcohol abuse and its related clinical conditions. (orig.)

  11. Alcohol-induced changes in the brain as assessed by MRI and CT

    Geibprasert, Sasikhan; Gallucci, Massimo; Krings, Timo

    2010-01-01

    This review provides an overview of structural magnetic resonance imaging and computed tomography findings of direct and indirect alcohol-related toxic effects on the brain. In addition to ethanol-related changes to the brain, this article will also describe imaging findings in the acute setting of methanol and ethylene glycol poisoning. Alcohol will lead to brain atrophy, osmotic myelinolysis, Marchiafava-Bignami disease and, especially when related to malnutrition, may also cause Wernicke encephalopathy. Brain atrophy can be reversible if alcohol abuse is stopped. If not treated, Wernicke encephalopathy can lead to coma and death and an early diagnosis is important for immediate initiation of thiamine substitution. As clinical symptoms are often unspecific, the radiologist plays an important role in the detection of alcohol abuse and its related clinical conditions. (orig.)

  12. Alcohol Alert

    ... of Alcohol Consumption Alcohol's Effects on the Body Alcohol Use Disorder Fetal Alcohol Exposure Support & Treatment Alcohol Policy Special ... 466 KB] No. 81: Exploring Treatment Options for Alcohol Use Disorders [ PDF - 539K] No. 80: Alcohol and HIV/AIDS: ...

  13. Hyphal-like extension and pseudohyphal formation in industrial strains of yeasts induced by isoamyl alcohol

    Ceccato-Antonini, Sandra Regina; Silva, Paula Cristina da

    2002-01-01

    Yeasts can produce pseudohyphae and hyphal-like extensions under certain growth conditions like isoamyl alcohol (IAA) induction, a chief constituent of fusel oil, which is a subproduct from the ethanolic fermentation. The morphology switch from yeast to a filamentous form can be troublesome to the process. In this work it was studied the influence of fusel alcohols, nitrogen sources (ammonium sulphate and leucine) and glifosate (a chemical maturator for sugar cane) added to a complex medium o...

  14. Mathematical simulation of the kinetics of radiation induced hydroxyalkylation of aliphatic saturated alcohols

    Silaev, M.M.; Bugaenko, L.T.

    1992-01-01

    The paper reports on the development of the kinetics of radiation hydroxymethylation and hydroxypropylation chain processes relating to aliphatic saturated alcohols in the γ-radiolysis of the alcohol-unsaturated compound systems to give 1,2- and 1,4-diols respectively. These processes were simulated mathematically. The kinetic curves computed are in good agreement with the experimental dependences. The kinetic parameters of the processes, including the rate constants for the addition of α-hydroxyalkyl radicals from the saturated alcohols to the double bond of the unsaturated component, viz formaldehyde or 2-propene-1-ol in the systems, were estimated. The constants (in dm 3 /mol.s) for the saturated alcohol-formaldehyde systems incorporating ethanol as the saturated alcohol were found to be (1.5±0.3).10 4 at 413 K and (2.1±0.5).10 4 at 443K; incorporating 1-propanol- (6.0±1.3).10 3 at 413 K; for the saturated alcohol-2-propene-1-ol systems incorporating methanol, ethanol, 1- and 2-propanol-(2.5±0.3).10 4 , (6.5±0.9).10 4 , (2.7±0.4).10 4 and (1.0±0.1).10 5 , respectively, at 433 K. (author)

  15. Binge Drinking and the Young Brain: A Mini Review of the Neurobiological Underpinnings of Alcohol-Induced Blackout

    Daniel F. Hermens

    2018-01-01

    Full Text Available Binge drinking has significant effects on memory, particularly with regards to the transfer of information to long-term storage. Partial or complete blocking of memory formation is known as blackout. Youth represents a critical period in brain development that is particularly vulnerable to alcohol misuse. Animal models show that the adolescent brain is more vulnerable to the acute and chronic effects of alcohol compared with the adult brain. This mini-review addresses the neurobiological underpinnings of binge drinking and associated memory loss (blackout in the adolescent and young adult period. Although the extent to which there are pre-existing versus alcohol-induced neurobiological changes remains unclear, it is likely that repetitive binge drinking in youth has detrimental effects on cognitive and social functioning. Given its role in learning and memory, the hippocampus is a critical region with neuroimaging research showing notable changes in this structure associated with alcohol misuse in young people. There is a great need for earlier identification of biological markers associated with alcohol-related brain damage. As a means to assess in vivo neurochemistry, magnetic resonance spectroscopy (MRS has emerged as a particularly promising technique since changes in neurometabolites often precede gross structural changes. Thus, the current paper addresses how MRS biomarkers of neurotransmission (glutamate, GABA and oxidative stress (indexed by depleted glutathione in the hippocampal region of young binge drinkers may underlie propensity for blackouts and other memory impairments. MRS biomarkers may have particular utility in determining the acute versus longer-term effects of binge drinking in young people.

  16. A procedure to observe context-induced renewal of pavlovian-conditioned alcohol-seeking behavior in rats.

    Maddux, Jean-Marie; Lacroix, Franca; Chaudhri, Nadia

    2014-09-19

    Environmental contexts in which drugs of abuse are consumed can trigger craving, a subjective Pavlovian-conditioned response that can facilitate drug-seeking behavior and prompt relapse in abstinent drug users. We have developed a procedure to study the behavioral and neural processes that mediate the impact of context on alcohol-seeking behavior in rats. Following acclimation to the taste and pharmacological effects of 15% ethanol in the home cage, male Long-Evans rats receive Pavlovian discrimination training (PDT) in conditioning chambers. In each daily (Mon-Fri) PDT session, 16 trials each of two different 10 sec auditory conditioned stimuli occur. During one stimulus, the CS+, 0.2 ml of 15% ethanol is delivered into a fluid port for oral consumption. The second stimulus, the CS-, is not paired with ethanol. Across sessions, entries into the fluid port during the CS+ increase, whereas entries during the CS- stabilize at a lower level, indicating that a predictive association between the CS+ and ethanol is acquired. During PDT each chamber is equipped with a specific configuration of visual, olfactory and tactile contextual stimuli. Following PDT, extinction training is conducted in the same chamber that is now equipped with a different configuration of contextual stimuli. The CS+ and CS- are presented as before, but ethanol is withheld, which causes a gradual decline in port entries during the CS+. At test, rats are placed back into the PDT context and presented with the CS+ and CS- as before, but without ethanol. This manipulation triggers a robust and selective increase in the number of port entries made during the alcohol predictive CS+, with no change in responding during the CS-. This effect, referred to as context-induced renewal, illustrates the powerful capacity of contexts associated with alcohol consumption to stimulate alcohol-seeking behavior in response to Pavlovian alcohol cues.

  17. Metagenomic analyses of alcohol induced pathogenic alterations in the intestinal microbiome and the effect of Lactobacillus rhamnosus GG treatment.

    Lara Bull-Otterson

    Full Text Available Enteric dysbiosis plays an essential role in the pathogenesis of alcoholic liver disease (ALD. Detailed characterization of the alterations in the gut microbiome is needed for understanding their pathogenic role in ALD and developing effective therapeutic approaches using probiotic supplementation. Mice were fed liquid Lieber-DeCarli diet without or with alcohol (5% v/v for 6 weeks. A subset of mice were administered the probiotic Lactobacillus rhamnosus GG (LGG from 6 to 8 weeks. Indicators of intestinal permeability, hepatic steatosis, inflammation and injury were evaluated. Metagenomic analysis of the gut microbiome was performed by analyzing the fecal DNA by amplification of the V3-V5 regions of the 16S rRNA gene and large-scale parallel pyrosequencing on the 454 FLX Titanium platform. Chronic ethanol feeding caused a decline in the abundance of both Bacteriodetes and Firmicutes phyla, with a proportional increase in the gram negative Proteobacteria and gram positive Actinobacteria phyla; the bacterial genera that showed the biggest expansion were the gram negative alkaline tolerant Alcaligenes and gram positive Corynebacterium. Commensurate with the qualitative and quantitative alterations in the microbiome, ethanol caused an increase in plasma endotoxin, fecal pH, hepatic inflammation and injury. Notably, the ethanol-induced pathogenic changes in the microbiome and the liver were prevented by LGG supplementation. Overall, significant alterations in the gut microbiome over time occur in response to chronic alcohol exposure and correspond to increases in intestinal barrier dysfunction and development of ALD. Moreover, the altered bacterial communities of the gut may serve as significant therapeutic target for the prevention/treatment of chronic alcohol intake induced intestinal barrier dysfunction and liver disease.

  18. Influence of UV and Gamma radiations on the induced birefringence of stretched poly(vinyl) alcohol foils

    Nechifor, Cristina-Delia; Zelinschi, Carmen Beatrice; Dorohoi, Dana-Ortansa

    2014-03-01

    The aim of our paper is to evidence the influence of Gamma and UV radiations on the induced birefringence of poly(vinyl alcohol) stretched foils. Thin foils of PVA were prepared and dried without modifying their surfaces. The polymeric foils were irradiated from 15 min to 6 h using UV and Gamma radiations. The induced by stretching under heating birefringence of PVA films was measured at λ = 589.3 nm with a Babinet Compensator. Physico-chemical processes (photo stabilization, photo degradation, oxidation) induced by irradiation of polymer matrix influence both the stretching degree and the anisotropy of etired foils. An increase of birefringence versus the stretching ratio of the PVA foils was evidenced for all studied samples. The dependence of the birefringence on the exposure time, stretching ratio and nature of radiation was also confirmed.

  19. Nrf2-mediated antioxidant response by ethanolic extract of Sida cordifolia provides protection against alcohol-induced oxidative stress in liver by upregulation of glutathione metabolism.

    Rejitha, S; Prathibha, P; Indira, M

    2015-03-01

    Objective The study aimed to evaluate the antioxidant property of ethanolic extract of Sida cordifolia (SAE) on alcohol-induced oxidative stress and to elucidate its mechanism of action. Methods Male albino rats of the Sprague-Dawley strain were grouped into four: (1) control, (2) alcohol (4 g/kg body weight), (3) SAE (50 mg/100 g body weight), and (4) alcohol (4 g/kg body weight) + SAE (50 mg/100 g body weight). Alcohol and SAE were given orally each day by gastric intubation. The duration of treatment was 90 days. Results The activities of toxicity markers in liver and serum increased significantly in alcohol-treated rats and to a lesser extent in the group administered SAE + alcohol. The activity of alcohol dehydrogenase and the reactive oxygen species level were increased significantly in alcohol-treated rats but attenuated in the SAE co-administered group. Oxidative stress was increased in alcohol-treated rats as evidenced by the lowered activities of antioxidant enzymes, decreased level of reduced glutathione (GSH), increased lipid peroxidation products, and decreased expression of γ-glutamyl cysteine synthase in liver. The co-administration of SAE with alcohol almost reversed these changes. The activity of glutathione-S-transferase and translocation of Nrf2 from cytosol to nucleus in the liver was increased in both the alcohol and alcohol + SAE groups, but the maximum changes were observed in the latter group. Discussion The SAE most likely elicits its antioxidant potential by reducing oxidative stress, enhancing the translocation of Nrf2 to nucleus and thereby regulating glutathione metabolism, leading to enhanced GSH content.

  20. Musculus gastrocnemius tetanus kinetics in alcohol-intoxicated rats with experimentally-induced hindlimb vascular ischemia under conditions of low-frequence muscle fatigue

    O. A. Melnychuk

    2014-04-01

    Full Text Available Alcohol intoxication and ischemic injury of skeletal muscles often accompany each other. It is shown that patients hospitalized with chronic alcoholism develop muscle fatigue. Skeletal muscle dysfunction in alcohol-dependent patients is caused by ethanol-associated myofibrillar atrophy and metabolic disbalance, while compression-ischemic lesions result from unconsciousness of the patient, in case of taking the critical alcohol dose. Therefore, the aim of this study is to discover typical m. gastrocnemius (cap. med. tetanic kinetics changes in alcohol intoxicated rats with experimentally induced vascular ischemia of hindlimb muscles under conditions of low-frequency progressive muscle fatigue. Experiments were carried out on 10 young male Wistar rats (149.5 ± 5.8 g kept under standard vivarium conditions and diet. The investigation was conducted in two phases: chronic (30 days and acute (3 hours experiment. All surgical procedures were carried out aseptically under general anesthesia. Ishemic m. gastrocnemius (cap. med. tetanic kinetic changes and force productivity in alcohol intoxicated rats were investigated in the isometric mode, with direct electrical stimulation. The fatigue of m. gastrocnemius (cap. med. was evaluated by three characteristic criteria: the first sag effect, the secondary force rise, the second sag effect. There have been 10 similar experiments: 5 series in each study group with 10 tetanic runs in each series. The highest amplitude of the native m. gastrocnemius (cap. med. tetanus relative to isoline was taken as 100% force response. The same pattern of m. gastrocnemius (cap. med. low-frequency fatigue development was found in both rat groups under study. It is evidenced by the absence of substantial m. gastrocnemius (cap. med. tetanus kinetics differences in alcohol intoxicated rats, compared with non-alcohol intoxicated rats during fatigue test. However, the appreciable m. gastrocnemius (cap. med. tetanic force reduction

  1. Balconing: An alcohol-induced craze that injures tourists. Characterization of the phenomenon.

    Segura-Sampedro, Juan José; Pineño-Flores, Cristina; García-Pérez, Jose María; Jiménez-Morillas, Patricia; Morales-Soriano, Rafael; González-Argente, Xavier

    2017-07-01

    Balconing is the term that has been given to consciously jumping into a swimming pool from a balcony or falling from height while climbing from one balcony to another in hotels during holidays METHOD: A 5 years retrospective study was conducted in a tertiary referral centre for severe trauma in the Balearic Islands, where balconing is endemic. Demographic data such as age, sex, nationality, personal records, alcohol or drug consumption, height of the fall and season of the year were collected. Scales of trauma severity and mortality rates were also included. Most of the patients were males, 45 (97.83%), aged 24.20±5.98years, 28 of them of British nationality (60.87%). In 44 (95.65%) cases, alcohol consumption was present accompanied by other drugs in 17 (36.96%) cases. The mean height of the fall was approximately 3 floors. Only 6 (13.04%) were intentional jumpers whereas 40 (86.96%) fell while trying to reach another balcony. Balconing is a new injury mechanism for alcohol-related falls from heights. Alcohol and other drug consumption are almost always involved, so balconing could be addressed as another consequence of alcohol abuse and binge drinking. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Drunk bugs: Chronic vapour alcohol exposure induces marked changes in the gut microbiome in mice.

    Peterson, Veronica L; Jury, Nicholas J; Cabrera-Rubio, Raúl; Draper, Lorraine A; Crispie, Fiona; Cotter, Paul D; Dinan, Timothy G; Holmes, Andrew; Cryan, John F

    2017-04-14

    The gut microbiota includes a community of bacteria that play an integral part in host health and biological processes. Pronounced and repeated findings have linked gut microbiome to stress, anxiety, and depression. Currently, however, there remains only a limited set of studies focusing on microbiota change in substance abuse, including alcohol use disorder. To date, no studies have investigated the impact of vapour alcohol administration on the gut microbiome. For research on gut microbiota and addiction to proceed, an understanding of how route of drug administration affects gut microbiota must first be established. Animal models of alcohol abuse have proven valuable for elucidating the biological processes involved in addiction and alcohol-related diseases. This is the first study to investigate the effect of vapour route of ethanol administration on gut microbiota in mice. Adult male C57BL/6J mice were exposed to 4 weeks of chronic intermittent vapourized ethanol (CIE, N=10) or air (Control, N=9). Faecal samples were collected at the end of exposure followed by 16S sequencing and bioinformatic analysis. Robust separation between CIE and Control was seen in the microbiome, as assessed by alpha (pgut microbiota in mice. Significant increases in genus Alistipes (pgut-brain axis and align with previous research showing similar microbiota alterations in inflammatory states during alcoholic hepatitis and psychological stress. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Oral metformin-ascorbic acid co-administration ameliorates alcohol-induced hepatotoxicity in rats.

    Adeneye, A A; Benebo, A S

    2007-01-01

    Alcoholic liver disease remains a major cause of liver failure worldwide with no available curative or prophylactic therapy as at present. High dose metformin is reported to ameliorate liver injuries in both human and animal models of acute and chronic alcoholic liver injuries. The aim of the present in vivo animal study was to determine whether metformin-ascorbic acid co-administration also prevents alcoholic hepatotoxicity in chronic alcohol exposure. In the present study, ameliorating effect of 200 mg/ kg/day of ascorbic acid (Asc), 500 mg/kg/day of metformin (Met) and their co-administration (Met-Asc) were investigated in 5 groups of 50% ethanol-treated male Wistar rats for 2 weeks of the experiment. The body weight of each rat was taken on days 1, 7, and 14 of the experiment, respectively. On day 15, fasted blood samples for plasma lipids and liver enzyme markers were collected via cardiac puncture from the rats under diethyl ether anaesthesia. Results showed that administration of graded oral doses of 50% ethanol for 14 days significantly (pcholesterol (PTC), high density lipoprotein (HDL-c), and low density lipoprotein (LDL-c). However, these elevations were significantly (pascorbic acid co-administration protected the liver against the deleterious effects of chronic high dose alcohol and the hepatoprotective effect of Met-Asc appeared to be due mainly to the metformin molecule of the drug combination. However, further studies would be required to evaluate the mechanisms underlying the observed effects.

  4. Effect of specific amino acids on hepatic lipid metabolism in fructose-induced non-alcoholic fatty liver disease.

    Jegatheesan, Prasanthi; Beutheu, Stéphanie; Ventura, Gabrielle; Sarfati, Gilles; Nubret, Esther; Kapel, Nathalie; Waligora-Dupriet, Anne-Judith; Bergheim, Ina; Cynober, Luc; De-Bandt, Jean-Pascal

    2016-02-01

    Fructose diets have been shown to induce insulin resistance and to alter liver metabolism and gut barrier function, ultimately leading to non-alcoholic fatty liver disease. Citrulline, Glutamine and Arginine may improve insulin sensitivity and have beneficial effects on gut trophicity. Our aim was to evaluate their effects on liver and gut functions in a rat model of fructose-induced non-alcoholic fatty liver disease. Male Sprague-Dawley rats (n = 58) received a 4-week fructose (60%) diet or standard chow with or without Citrulline (0.15 g/d) or an isomolar amount of Arginine or Glutamine. All diets were made isonitrogenous by addition of non-essential amino acids. At week 4, nutritional and metabolic status (plasma glucose, insulin, cholesterol, triglycerides and amino acids, net intestinal absorption) was determined; steatosis (hepatic triglycerides content, histological examination) and hepatic function (plasma aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, bilirubin) were assessed; and gut barrier integrity (myeloperoxidase activity, portal endotoxemia, tight junction protein expression and localization) and intestinal and hepatic inflammation were evaluated. We also assessed diets effects on caecal microbiota. In these experimental isonitrogenous fructose diet conditions, fructose led to steatosis with dyslipidemia but without altering glucose homeostasis, liver function or gut permeability. Fructose significantly decreased Bifidobacterium and Lactobacillus and tended to increase endotoxemia. Arginine and Glutamine supplements were ineffective but Citrulline supplementation prevented hypertriglyceridemia and attenuated liver fat accumulation. While nitrogen supply alone can attenuate fructose-induced non-alcoholic fatty liver disease, Citrulline appears to act directly on hepatic lipid metabolism by partially preventing hypertriglyceridemia and steatosis. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition

  5. A Comparison Study of Quetiapine and Risperidone's Effectiveness and Safety on Treating Alcohol-induced Mental Disorder.

    Lv, Bei; Duan, Haishui

    2016-08-25

    Compared with Risperidone, Quetiapine's effectiveness and safety on treating alcohol-induced mental disorder is still unclear. To investigate the clinical effectiveness and safety of Quetiapine on treating alcohol-induced mental disorder. One hundred and forty-eight patients with alcohol-induced mental disorder were divided into the experimental group (75 patients) and the control group (73 patients) by the treatments they received. The patients in the experimental group were treated with Quetiapine by taking it three times per day orally. The mean (sd) maintenance dose was 151.2(27.3) mg/d, and the treatment cycle was 6 weeks. Patients in the control group received Risperidone once per day orally with a mean (sd) maintenance dose being 2.3(0.9) mg/d, and the treatment cycle was 6 weeks as well. The PANSS scale was used to assess patients' before and after treatment. The researchers also observed any adverse reactions in both treatment strategies and evaluated the effectiveness and safety of both treatment strategies. The mean (sd) PANSS scale score of the experimental group after two weeks of treatment was 71.9 (10.2), which was clearly better than the mean (sd) score before treatment (82.6 [11.4]), and was significantly better than the control group's mean (sd) score after two weeks (76.5[12.8]). Also, the experimental group's scores after 4 weeks of treatment and 6 weeks of treatment were significantly better than the control group. The experimental group's efficacy rate (94.7%) was higher than the control group's (90.4%); the cure rate of the experimental group (33.3%) was higher than that of the control group (24.7%), and the difference was statistically significant. The rates of adverse reactions in the experimental and control groups were 13.3% and 19.2% respectively, and they were significantly different from each other. Treating alcohol-induced mental disorder with Quetiapine is more effective than treating it with Risperidone. Quetiapine can improve

  6. FT-IR study of gamma-radiation induced degradation of polyvinyl alcohol (PVA) and PVA/humic acids blends

    Ilcin, M.; Hola, O.; Bakajova, B.; Kucerik, J.

    2010-01-01

    Samples of pure polyvinyl alcohol (PVA) and PVA doped with humic acids were exposed to gamma radiation. Gamma rays induced the degradation of the pure polymer. Degradation changes were observed using ATR FT-IR equipment. Dehydration, double bond creation, and their subsequent oxidation (surrounding atmosphere was air) were found out. Also, other degradation reactions (e.g. chain scission, cyclization) occur simultaneously. Formation of C=C and C=O bonds is apparent from FT-IR spectra. In contrast the presence of humic acids in the PVA sample showed stabilizing effect on PVA structure within the concentration range 0.5-10%. (author)

  7. Drug-Induced Apoptosis: Mechanism by which Alcohol and Many Other Drugs Can Disrupt Brain Development

    John W. Olney

    2013-07-01

    Full Text Available Maternal ingestion of alcohol during pregnancy can cause a disability syndrome termed Fetal Alcohol Spectrum Disorder (FASD, which may include craniofacial malformations, structural pathology in the brain, and a variety of long-term neuropsychiatric disturbances. There is compelling evidence that exposure to alcohol during early embryogenesis (4th week of gestation can cause excessive death of cell populations that are essential for normal development of the face and brain. While this can explain craniofacial malformations and certain structural brain anomalies that sometimes accompany FASD, in many cases these features are absent, and the FASD syndrome manifests primarily as neurobehavioral disorders. It is not clear from the literature how alcohol causes these latter manifestations. In this review we will describe a growing body of evidence documenting that alcohol triggers widespread apoptotic death of neurons and oligodendroglia (OLs in the developing brain when administered to animals, including non-human primates, during a period equivalent to the human third trimester of gestation. This cell death reaction is associated with brain changes, including overall or regional reductions in brain mass, and long-term neurobehavioral disturbances. We will also review evidence that many drugs used in pediatric and obstetric medicine, including general anesthetics (GAs and anti-epileptics (AEDs, mimic alcohol in triggering widespread apoptotic death of neurons and OLs in the third trimester-equivalent animal brain, and that human children exposed to GAs during early infancy, or to AEDs during the third trimester of gestation, have a significantly increased incidence of FASD-like neurobehavioral disturbances. These findings provide evidence that exposure of the developing human brain to GAs in early infancy, or to alcohol or AEDs in late gestation, can cause FASD-like neurodevelopmental disability syndromes. We propose that the mechanism by which

  8. 76 FR 17140 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    2011-03-28

    ... Alcohol Abuse and Alcoholism; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory... Alcohol Abuse and Alcoholism Special Emphasis Panel; RFA-AA-11-02 Alcohol Induced Metabolic and Hepatic...: Philippe Marmillot, PhD, Scientific Review Officer, National Institute on Alcohol Abuse and Alcoholism...

  9. Pharmacological activation/inhibition of the cannabinoid system affects alcohol withdrawal-induced neuronal hypersensitivity to excitotoxic insults.

    Marina Rubio

    Full Text Available Cessation of chronic ethanol consumption can increase the sensitivity of the brain to excitotoxic damages. Cannabinoids have been proposed as neuroprotectants in different models of neuronal injury, but their effect have never been investigated in a context of excitotoxicity after alcohol cessation. Here we examined the effects of the pharmacological activation/inhibition of the endocannabinoid system in an in vitro model of chronic ethanol exposure and withdrawal followed by an excitotoxic challenge. Ethanol withdrawal increased N-methyl-D-aspartate (NMDA-evoked neuronal death, probably by altering the ratio between GluN2A and GluN2B NMDA receptor subunits. The stimulation of the endocannabinoid system with the cannabinoid agonist HU-210 decreased NMDA-induced neuronal death exclusively in ethanol-withdrawn neurons. This neuroprotection could be explained by a decrease in NMDA-stimulated calcium influx after the administration of HU-210, found exclusively in ethanol-withdrawn neurons. By contrast, the inhibition of the cannabinoid system with the CB1 receptor antagonist rimonabant (SR141716 during ethanol withdrawal increased death of ethanol-withdrawn neurons without any modification of NMDA-stimulated calcium influx. Moreover, chronic administration of rimonabant increased NMDA-stimulated toxicity not only in withdrawn neurons, but also in control neurons. In summary, we show for the first time that the stimulation of the endocannabinoid system is protective against the hyperexcitability developed during alcohol withdrawal. By contrast, the blockade of the endocannabinoid system is highly counterproductive during alcohol withdrawal.

  10. Fluoxetine regulates mTOR signalling in a region-dependent manner in depression-like mice

    Liu, Xiao-Long; Luo, Liu; Mu, Rong-Hao; Liu, Bin-Bin; Geng, Di; Liu, Qing; Yi, Li-Tao

    2015-01-01

    Previous studies have demonstrated that the mammalian target of rapamycin (mTOR) signaling pathway has an important role in ketamine-induced, rapid antidepressant effects despite the acute administration of fluoxetine not affecting mTOR phosphorylation in the brain. However, the effects of long-term fluoxetine treatment on mTOR modulation have not been assessed to date. In the present study, we examined whether fluoxetine, a type of commonly used antidepressant agent, alters mTOR signaling following chronic administration in different brain regions, including the frontal cortex, hippocampus, amygdala and hypothalamus. We also investigated whether fluoxetine enhanced synaptic protein levels in these regions via the activation of the mTOR signaling pathway and its downstream regulators, p70S6K and 4E-BP-1. The results indicated that chronic fluoxetine treatment attenuated the chronic, unpredictable, mild stress (CUMS)-induced mTOR phosphorylation reduction in the hippocampus and amygdala of mice but not in the frontal cortex or the hypothalamus. Moreover, the CUMS-decreased PSD-95 and synapsin I levels were reversed by fluoxetine, and these effects were blocked by rapamycin only in the hippocampus. In conclusion, our findings suggest that chronic treatment with fluoxetine can induce synaptic protein expression by activating the mTOR signaling pathway in a region-dependent manner and mainly in the hippocampus. PMID:26522512

  11. TLR4 response mediates ethanol-induced neurodevelopment alterations in a model of fetal alcohol spectrum disorders.

    Pascual, María; Montesinos, Jorge; Montagud-Romero, Sandra; Forteza, Jerónimo; Rodríguez-Arias, Marta; Miñarro, José; Guerri, Consuelo

    2017-07-24

    ). These changes are associated with long-term behavioral impairments, in the 66-day-old alcohol-exposed pups. TLR4-deficient mice are protected against ethanol-induced cytokine/chemokine production in alcohol-treated dams and offspring, along with synaptic and myelin alterations, and the log-term behavioral dysfunction induced by ethanol in offspring. These results suggest that the immune system activation, through the TLR4 response, might play an important role in the neurodevelopmental defects in FASD.

  12. An integrated perspective on diabetic, alcoholic, and drug-induced neuropathy, etiology, and treatment in the US

    Zeng L

    2017-01-01

    Full Text Available Lily Zeng,1 Doungkamol Alongkronrusmee,2 Richard M van Rijn2 1Department of Internal Medicine, Vanderbilt University Medical Center, Nashville, TN, 2Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN, USA Abstract: Neuropathic pain (NeuP is a syndrome that results from damaged nerves and/or aberrant regeneration. Common etiologies of neuropathy include chronic illnesses and medication use. Chronic disorders, such as diabetes and alcoholism, can cause neuronal injury and consequently NeuP. Certain medications with antineoplastic effects also carry an exquisitely high risk for neuropathy. These culprits are a few of many that are fueling the NeuP epidemic, which currently affects 7%–10% of the population. It has been estimated that approximately 10% and 7% of US adults carry a diagnosis of diabetes and alcohol disorder, respectively. Despite its pervasiveness, many physicians are unfamiliar with adequate treatment of NeuP, partly due to the few reviews that are available that have integrated basic science and clinical practice. In light of the recent Centers for Disease Control and Prevention guidelines that advise against the routine use of μ-opioid receptor-selective opioids for chronic pain management, such a review is timely. Here, we provide a succinct overview of the etiology and treatment options of diabetic and alcohol- and drug-induced neuropathy, three different and prevalent neuropathies fusing the combined clinical and preclinical pharmacological expertise in NeuP of the authors. We discuss the anatomy of pain and pain transmission, with special attention to key ion channels, receptors, and neurotransmitters. An understanding of pain neurophysiology will lead to a better understanding of the rationale for the effectiveness of current treatment options, and may lead to better diagnostic tools to help distinguish types of neuropathy. We close with a discussion of ongoing research

  13. Deletion of tumor progression locus 2 attenuates alcohol induced hepatic inflammation

    BACKGROUND: The pathogenesis of alcoholic liver disease (ALD) involves the interaction of several inflammatory signaling pathways. Tumor progression locus 2 (TPL2), also known as Cancer Osaka Thyroid (COT) and MAP3K8, is a serine threonine kinase that functions as a critical regulator of inflammator...

  14. Rat Strain Differences in Susceptibility to Alcohol-Induced Chronic Liver Injury and Hepatic Insulin Resistance

    Sarah M. DeNucci

    2010-01-01

    Full Text Available The finding of more severe steatohepatitis in alcohol fed Long Evans (LE compared with Sprague Dawley (SD and Fisher 344 (FS rats prompted us to determine whether host factors related to alcohol metabolism, inflammation, and insulin/IGF signaling predict proneness to alcohol-mediated liver injury. Adult FS, SD, and LE rats were fed liquid diets containing 0% or 37% (calories ethanol for 8 weeks. Among controls, LE rats had significantly higher ALT and reduced GAPDH relative to SD and FS rats. Among ethanol-fed rats, despite similar blood alcohol levels, LE rats had more pronounced steatohepatitis and fibrosis, higher levels of ALT, DNA damage, pro-inflammatory cytokines, ADH, ALDH, catalase, GFAP, desmin, and collagen expression, and reduced insulin receptor binding relative to FS rats. Ethanol-exposed SD rats had intermediate degrees of steatohepatitis, increased ALT, ADH and profibrogenesis gene expression, and suppressed insulin receptor binding and GAPDH expression, while pro-inflammatory cytokines were similarly increased as in LE rats. Ethanol feeding in FS rats only reduced IL-6, ALDH1–3, CYP2E1, and GAPDH expression in liver. In conclusion, susceptibility to chronic steatohepatitis may be driven by factors related to efficiency of ethanol metabolism and degree to which ethanol exposure causes hepatic insulin resistance and cytokine activation.

  15. Regulation of Alcohol Extinction and Cue-Induced Reinstatement by Specific Projections among Medial Prefrontal Cortex, Nucleus Accumbens, and Basolateral Amygdala.

    Keistler, Colby R; Hammarlund, Emma; Barker, Jacqueline M; Bond, Colin W; DiLeone, Ralph J; Pittenger, Christopher; Taylor, Jane R

    2017-04-26

    The ability to inhibit drinking is a significant challenge for recovering alcoholics, especially in the presence of alcohol-associated cues. Previous studies have demonstrated that the regulation of cue-guided alcohol seeking is mediated by the basolateral amygdala (BLA), nucleus accumbens (NAc), and medial prefrontal cortex (mPFC). However, given the high interconnectivity between these structures, it is unclear how mPFC projections to each subcortical structure, as well as projections between BLA and NAc, mediate alcohol-seeking behaviors. Here, we evaluate how cortico-striatal, cortico-amygdalar, and amygdalo-striatal projections control extinction and relapse in a rat model of alcohol seeking. Specifically, we used a combinatorial viral technique to express diphtheria toxin receptors in specific neuron populations based on their projection targets. We then used this strategy to create directionally selective ablations of three distinct pathways after acquisition of ethanol self-administration but before extinction and reinstatement. We demonstrate that ablation of mPFC neurons projecting to NAc, but not BLA, blocks cue-induced reinstatement of alcohol seeking and neither pathway is necessary for extinction of responding. Further, we show that ablating BLA neurons that project to NAc disrupts extinction of alcohol approach behaviors and attenuates reinstatement. Together, these data provide evidence that the mPFC→NAc pathway is necessary for cue-induced reinstatement of alcohol seeking, expand our understanding of how the BLA→NAc pathway regulates alcohol behavior, and introduce a new methodology for the manipulation of target-specific neural projections. SIGNIFICANCE STATEMENT The vast majority of recovering alcoholics will relapse at least once and understanding how the brain regulates relapse will be key to developing more effective behavior and pharmacological therapies for alcoholism. Given the high interconnectivity of cortical, striatal, and limbic

  16. Statin therapy exacerbates alcohol-induced constriction of cerebral arteries via modulation of ethanol-induced BK channel inhibition in vascular smooth muscle.

    Simakova, Maria N; Bisen, Shivantika; Dopico, Alex M; Bukiya, Anna N

    2017-12-01

    Statins constitute the most commonly prescribed drugs to decrease cholesterol (CLR). CLR is an important modulator of alcohol-induced cerebral artery constriction (AICAC). Using rats on a high CLR diet (2% CLR) we set to determine whether atorvastatin administration (10mg/kg daily for 18-23weeks) modified AICAC. Middle cerebral arteries were pressurized in vitro at 60mmHg and AICAC was evoked by 50mM ethanol, that is within the range of blood alcohol detected in humans following moderate-to-heavy drinking. AICAC was evident in high CLR+atorvastatin group but not in high CLR diet+placebo. Statin exacerbation of AICAC persisted in de-endothelialized arteries, and was blunted by CLR enrichment in vitro. Fluorescence imaging of filipin-stained arteries showed that atorvastatin decreased vascular smooth muscle (VSM) CLR when compared to placebo, this difference being reduced by CLR enrichment in vitro. Voltage- and calcium-gated potassium channels of large conductance (BK) are known VSM targets of ethanol, with their beta1 subunit being necessary for ethanol-induced channel inhibition and resulting AICAC. Ethanol-induced BK inhibition in excised membrane patches from freshly isolated myocytes was exacerbated in the high CLR diet+atorvastatin group when compared to high CLR diet+placebo. Unexpectedly, atorvastatin decreased the amount and function of BK beta1 subunit as documented by immunofluorescence imaging and functional patch-clamp studies. Atorvastatin exacerbation of ethanol-induced BK inhibition disappeared upon artery CLR enrichment in vitro. Our study demonstrates for the first time statin's ability to exacerbate the vascular effect of a widely consumed drug of abuse, this exacerbation being driven by statin modulation of ethanol-induced BK channel inhibition in the VSM via CLR-mediated mechanism. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Characterization of an alcoholic hepatic steatosis model induced by ethanol and high-fat diet in rats

    Carlos Eduardo Alves de Souza

    2015-06-01

    Full Text Available Alcoholic liver disease is characterized by a wide spectrum of liver damage, which increases when ethanol is associated with high-fat diets (HFD. This work aimed to establish a model of alcoholic hepatic steatosis (AHS by using a combination of 10% ethanol and sunflower seeds as the source of HFD. Male rats received water or 10% ethanol and regular chow diet and/or HFD, which consisted of sunflower seeds. The food consumption, liquid intake and body weight of the rats were monitored for 30 days. After this period, blood was collected for biochemical evaluation, and liver samples were collected for histological, mitochondrial enzyme activity and oxidative stress analyses. Our results indicated that the combination of 10% ethanol and HFD induced micro- and macrosteatosis and hepatocyte tumefaction, decreased the levels of reduced glutathione and glutathione S-transferase activity and increased the level of lipoperoxidation and superoxide dismutase activity. The mitochondrial oxidation of NADH and succinate were partially inhibited. Complexes I and II were the main inhibition sites. Hepatic steatosis was successfully induced after 4 weeks of the diet, and the liver function was modified. The combination of 10% ethanol and sunflower seeds as an HFD produced an inexpensive model to study AHS in rats.

  18. Inhibition of CYP2E1 attenuates chronic alcohol intake-induced myocardial contractile dysfunction and apoptosis.

    Zhang, Rong-Huai; Gao, Jian-Yuan; Guo, Hai-Tao; Scott, Glenda I; Eason, Anna R; Wang, Xiao-Ming; Ren, Jun

    2013-01-01

    Alcohol intake is associated with myocardial contractile dysfunction and apoptosis although the precise mechanism is unclear. This study was designed to examine the effect of the cytochrome P450 enzyme CYP2E1 inhibition on ethanol-induced cardiac dysfunction. Adult male mice were fed a 4% ethanol liquid or pair-fed control diet for 6weeks. Following 2weeks of diet feeding, a cohort of mice started to receive the CYP2E1 inhibitor diallyl sulfide (100mg/kg/d, i.p.) for the remaining feeding duration. Cardiac function was assessed using echocardiographic and IonOptix systems. Western blot analysis was used to evaluate CYP2E1, heme oxygenase-1 (HO-1), iNOS, the intracellular Ca(2+) regulatory proteins sarco(endo)plasmic reticulum Ca(2+)-ATPase, Na(+)Ca(2+) exchanger and phospholamban, pro-apoptotic protein cleaved caspase-3, Bax, c-Jun-NH(2)-terminal kinase (JNK) and apoptosis signal-regulating kinase (ASK-1). Ethanol led to elevated levels of CYP2E1, iNOS and phospholamban, decreased levels of HO-1 and Na(+)Ca(2+) exchanger, cardiac contractile and intracellular Ca(2+) defects, cardiac fibrosis, overt O(2)(-) production, and apoptosis accompanied with increased phosphorylation of JNK and ASK-1, the effects were significantly attenuated or ablated by diallyl sulfide. Inhibitors of JNK and ASK-1 but not HO-1 inducer or iNOS inhibitor obliterated ethanol-induced cardiomyocyte contractile dysfunction, substantiating a role for JNK and ASK-1 signaling in ethanol-induced myocardial injury. Taken together, these findings suggest that ethanol metabolism through CYP2E1 may contribute to the pathogenesis of alcoholic cardiomyopathy including myocardial contractile dysfunction, oxidative stress and apoptosis, possibly through activation of JNK and ASK-1 signaling. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. An iso-α-acid-rich extract from hops (Humulus lupulus) attenuates acute alcohol-induced liver steatosis in mice.

    Hege, Marianne; Jung, Finn; Sellmann, Cathrin; Jin, Chengjun; Ziegenhardt, Doreen; Hellerbrand, Claus; Bergheim, Ina

    2018-01-01

    Results of in vitro and in vivo studies suggest that consumption of beer is less harmful for the liver than consumption of spirits. It also has been suggested that secondary plant compounds derived from hops such as xanthohumol or iso-α-acids may have beneficial effects on the development of liver diseases of various etiologies. The aim of this study was to determine whether iso-α-acids consumed in doses achieved by "normal" beer consumption have beneficial effects on health. Female C57 Bl/6 J mice, pretreated for 4 d with an iso-α-acid-rich extract (∼30% iso-α-acids from hops, 0.75 mg/kg body weight), were fed one bolus of ethanol (6 g/kg body weight intragastric) or an iso-caloric maltodextrin solution. Markers of liver damage, toll-like receptor-4 signaling, and lipid peroxidation were determined. Furthermore, the effect of isohumulone on the lipopolysaccharide-dependent activation of J774 A.1 macrophages, used as a model of Kupffer cells, was determined. In the liver, acute ethanol administration led to a significant accumulation of fat (∼10-fold), which was accompanied by significantly higher inducible nitric oxide synthase protein level, elevated nitric oxide production, and increased plasminogen activator inhibitor 1 protein concentration when compared to controls. In mice pretreated with iso-α-acids, these effects of alcohol were markedly attenuated. Pretreatment of J774 A.1 macrophages with isohumulone significantly attenuated lipopolysaccharide-induced mRNA expression of inducible nitric oxide synthase and interleukin-6 as well as the release of nitric oxide. Taken together, iso-α-acids markedly attenuated the development of acute alcohol-induced damage in mice. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Fucoidan from Fucus vesiculosus Protects against Alcohol-Induced Liver Damage by Modulating Inflammatory Mediators in Mice and HepG2 Cells

    Jung Dae Lim

    2015-02-01

    Full Text Available Fucoidan is an l-fucose-enriched sulfated polysaccharide isolated from brown algae and marine invertebrates. In this study, we investigated the protective effect of fucoidan from Fucus vesiculosus on alcohol-induced murine liver damage. Liver injury was induced by oral administration of 25% alcohol with or without fucoidan (30 mg/kg or 60 mg/kg for seven days. Alcohol administration increased serum aspartate aminotransferase and alanine aminotransferase levels, but these increases were suppressed by the treatment of fucoidan. Transforming growth factor beta 1 (TGF-β1, a liver fibrosis-inducing factor, was highly expressed in the alcohol-fed group and human hepatoma HepG2 cell; however, the increase in TGF-β1 expression was reduced following fucoidan administration. Treatment with fucoidan was also found to significantly reduce the production of inflammation-promoting cyclooygenase-2 and nitric oxide, while markedly increasing the expression of the hepatoprotective enzyme, hemeoxygenase-1, on murine liver and HepG2 cells. Taken together, the antifibrotic and anti-inflammatory effects of fucoidan on alcohol-induced liver damage may provide valuable insights into developing new therapeutics or interventions.

  1. Carboxylesterase 1 Is Regulated by Hepatocyte Nuclear Factor 4α and Protects Against Alcohol- and MCD diet-induced Liver Injury.

    Xu, Jiesi; Xu, Yang; Li, Yuanyuan; Jadhav, Kavita; You, Min; Yin, Liya; Zhang, Yanqiao

    2016-04-14

    The liver is a major organ that controls hepatic and systemic homeostasis. Dysregulation of liver metabolism may cause liver injury. Previous studies have demonstrated that carboxylesterase 1 (CES1) regulates hepatic triglyceride metabolism and protects against liver steatosis. In the present study, we investigated whether CES1 played a role in the development of alcoholic liver disease (ALD) and methionine and choline-deficient (MCD) diet-induced liver injury. Both hepatocyte nuclear factor 4α (HNF4α) and CES1 were markedly reduced in patients with alcoholic steatohepatitis. Alcohol repressed both HNF4α and CES1 expression in primary hepatocytes. HNF4α regulated CES1 expression by directly binding to the proximal promoter of CES1. Global inactivation of CES1 aggravated alcohol- or MCD diet-induced liver inflammation and liver injury, likely as a result of increased production of acetaldehyde and reactive oxygen species and mitochondrial dysfunctions. Knockdown of hepatic CES1 exacerbated ethanol-induced steatohepatitis. These data indicate that CES1 plays a crucial role in protection against alcohol- or MCD diet-induced liver injury.

  2. Alcoholic extraction enables EPR analysis to characterize radiation-induced cellulosic signals in spices.

    Ahn, Jae-Jun; Sanyal, Bhaskar; Akram, Kashif; Kwon, Joong-Ho

    2014-11-19

    Different spices such as turmeric, oregano, and cinnamon were γ-irradiated at 1 and 10 kGy. The electron paramagnetic resonance (EPR) spectra of the nonirradiated samples were characterized by a single central signal (g = 2.006), the intensity of which was significantly enhanced upon irradiation. The EPR spectra of the irradiated spice samples were characterized by an additional triplet signal at g = 2.006 with a hyperfine coupling constant of 3 mT, associated with the cellulose radical. EPR analysis on various sample pretreatments in the irradiated spice samples demonstrated that the spectral features of the cellulose radical varied on the basis of the pretreatment protocol. Alcoholic extraction pretreatment produced considerable improvements of the EPR signals of the irradiated spice samples relative to the conventional oven and freeze-drying techniques. The alcoholic extraction process is therefore proposed as the most suitable sample pretreatment for unambiguous detection of irradiated spices by EPR spectroscopy.

  3. Inaccessibility of alcohol-induced cirrhosis of the liver to radiopharmaceutical methods of investigation

    Roh, T.G.

    1983-01-01

    Three cases of chronic alcohol abuse are described where the scintigrams recorded completely failed to visualise the hepatic structures. The female patients included in the study abused alcohol over a period of several years and the quantities consumed were far above the dose generally believed to cause cirrhosis in women. All of them displayed signs of advanced cirrhosis of the liver like portal hypertension, icterus, coagulation disorders, hepatic encephalopathy, etc. and the disease eventually led to the death of the patients. Hepatic scintiscanning was performed using Au198, Hg197, Tc99m sulfur colloid, Tc99m antimonial colloid as well as rose bengal iodine 131 tagged isotope; one patient was additionally subjected to radionuclide examination of the abdominal cavity. The causes of the described phenomenon still remain obscure. Damage to the reticuloendothelial system appears to be one of the predominant factors in the etiology of the disease. (TRV) [de

  4. Role of Hypothalamic-Pituitary-Adrenal axis and corticotropin-releasing factor stress system on cue-induced relapse to alcohol seeking.

    Galesi, Fernanda L; Ayanwuyi, Lydia O; Mijares, Miriam Garcia; Cippitelli, Andrea; Cannella, Nazzareno; Ciccocioppo, Roberto; Ubaldi, Massimo

    2016-10-05

    A large body of evidence has shown that the Corticotropin Releasing Factor (CRF) system, which plays a key role in stress modulation, is deeply involved in relapse to alcohol seeking induced by exposure to stressful events such as foot shock or yohimbine injections. Exposure to environmental cues is also known to be a trigger for alcohol relapse, nevertheless, the relationship between the relapse evoked by the cue-induced model and the CRF stress systems remains unclear. The purpose of this study was to evaluate, in male Wistar rats, the involvement of the CRF system and Hypothalamic-Pituitary-Adrenal (HPA) axis in relapse induced by environmental cues. Antalarmin, a selective CRF1 receptor antagonist, Metyrapone, a corticosterone (CORT) synthesis inhibitor and CORT were evaluated for their effects on the reinstatement test in a cue-induced relapse model. Antalarmin (20mg/kg) blocked relapse to alcohol seeking induced by environmental cues. Metyrapone (50 and 100mg/kg) also blocked relapse in Wistar rats but only at the highest dose (100mg/kg). Corticosterone had no effect on relapse at the doses tested. The results obtained from this study suggest that the CRF stress system and the HPA axis are involved in cue-induced alcohol relapse. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. The effects of diet-induced obesity on hepatocyte insulin signaling pathways and induction of non-alcoholic liver damage

    Sameer Fatani

    2011-03-01

    Full Text Available Sameer Fatani1, Imose Itua2, Paul Clark3, Christopher Wong3, Ebrahim K Naderali21Obesity Biology Unit, School of Clinical Sciences, University of Liverpool, Liverpool, UK; 2Department of Health and Applied Social Sciences, Liverpool Hope University, Hope Park, Liverpool UK; 3Aintree University Hospital NHS Foundation Trust, Longmoor Lane, Liverpool, UKAbstract: The prevalence of diet-induced obesity is increasing amongst adults and children worldwide, predisposing millions of people to an array of health problems that include metabolic syndrome, non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. In this study we used experimental animals to investigate the effects of dietary obesity on markers of hepatic insulin signaling as well as structural changes in hepatocytes. Adult male Wistar rats were randomized and assigned to either a control group or a test group. Controls were fed standard laboratory pelleted diet (chow-fed, while the test group had free access to a highly-palatable diet (HPD. After eight weeks, the HPD-fed animals were subdivided into three subgroups and their diets altered as follows: HPD-to-chow, HPD with the addition of fenofibrate given by oral gavage for a further seven weeks, or HPD with vehicle (1% carboxymethylcellulose at 1 mL/kg body weight given by oral gavage for a further seven weeks, respectively. Untreated diet-fed animals had significantly higher body weight, liver weight, and all measured metabolic profiles compared with chow-fed and treated diet-fed groups. Expression of kinases IRβ, IRS-1, AKt, eNOS, Shc and ERK1/2 were unaffected by obesity, while IRS-2 and P I3 kinase levels were significantly reduced in untreated HPD animals. Compared with chow-fed animals, steatosis and steatohepatitis were almost doubled in animals from untreated HPD, while removal of HPD and fenofibrate-treatment reduced steatosis by 40% and 80% respectively. These data suggest that diet-induced obesity affects

  6. Increased intestinal permeability to macromolecules and endotoxemia in patients with chronic alcohol abuse in different stages of alcohol-induced liver disease

    Parlesak, Alexandr; Schäfer, C.; Schütz, Tanja

    2000-01-01

    BACKGROUND/AIMS: No information is yet available about the influence of alcohol abuse on the translocation of larger molecules (Mr>1200) through the intestinal mucosa in man. The present study aimed to determine the intestinal permeability to macromolecules in patients with chronic alcohol abuse...... and mild to more advanced stages of liver disease, and to measure the concentration of endotoxins in the plasma, as these compounds derive from the intestinal flora and are suspected to contribute to the development of alcoholic liver disease (ALD). METHODS: The permeability to polyethylene glycol Mr 400......, Mr 1500, Mr 4000, and Mr 10,000 and endotoxin plasma concentrations were measured in 54 patients with alcoholic liver disease, 19 of them with cirrhosis, and in 30 non-alcoholic healthy controls. RESULTS: Permeability to polyethylene glycol Mr 400 was found to be unchanged in patients with ALD...

  7. Hyphal-like extension and pseudohyphal formation in industrial strains of yeasts induced by isoamyl alcohol

    Ceccato-Antonini Sandra Regina

    2002-01-01

    Full Text Available Yeasts can produce pseudohyphae and hyphal-like extensions under certain growth conditions like isoamyl alcohol (IAA induction, a chief constituent of fusel oil, which is a subproduct from the ethanolic fermentation. The morphology switch from yeast to a filamentous form can be troublesome to the process. In this work it was studied the influence of fusel alcohols, nitrogen sources (ammonium sulphate and leucine and glifosate (a chemical maturator for sugar cane added to a complex medium on some industrial strains of yeasts isolated from the fermentative process. Two industrial strains showed transition to hyphal-like extensions or pseudohyphae (clusters of cells upon addition of IAA from 0.3 to 0.9% /v. The alterations were reversible when the yeasts were reinoculated in YEPD without IAA. Although pseudohyphae are a result of nitrogen-limited medium, we observed them as a result of IAA addition. No influence of the nitrogen source or isopropilic alcohol or glifosate was detected for any strain studied in the concentrations used.

  8. Potential Biomarker Peptides Associated with Acute Alcohol-Induced Reduction of Blood Pressure

    Wakabayashi, Ichiro; Marumo, Mikio; Nonaka, Daisuke; Shimomura, Tomoko; Eguchi, Ryoji; Lee, Lyang-Ja; Tanaka, Kenji; Hatake, Katsuhiko

    2016-01-01

    The purpose of this study was to explore the peptides that are related to acute reduction of blood pressure after alcohol drinking. Venous blood was collected from male healthy volunteers before and after drinking white wine (3 ml/kg weight) containing 13% of ethanol. Peptidome analysis for serum samples was performed using a new target plate, BLOTCHIP®. Alcohol caused significant decreases in systolic and diastolic blood pressure levels at 45 min. The peptidome analysis showed that the levels of three peptides of m/z 1467, 2380 and 2662 changed significantly after drinking. The m/z 1467 and 2662 peptides were identified to be fragments of fibrinogen alpha chain, and the m/z 2380 peptide was identified to be a fragment of complement C4. The intensities of the m/z 2380 and m/z 1467 peptides before drinking were associated with % decreases in systolic and diastolic blood pressure levels at 45 min after drinking compared with the levels before drinking, while there were no significant correlations between the intensity of the m/z 2662 peptide and % decreases in systolic and diastolic blood pressure levels after drinking. The m/z 1467 and 2380 peptides are suggested to be markers for acute reduction of blood pressure after drinking alcohol. PMID:26815288

  9. Virgin coconut oil extract mitigates testicular-induced toxicity of alcohol use in antiretroviral therapy.

    Ogedengbe, O O; Naidu, E C S; Akang, E N; Offor, U; Onanuga, I O; Peter, A I; Jegede, A I; Azu, O O

    2018-04-14

    The consumption of alcohol by people living with HIV/AIDS is associated with a graver prognosis. Long-term use of antiretrovirals may have certain health challenges that may be aggravated by concomitant alcohol use. This study investigated virgin coconut oil (VCO) as an adjuvant to the deleterious effects of highly active antiretroviral therapy (HAART) and alcohol on the cyto-architecture and functioning of the testis. Forty adult male Sprague-Dawley rats, weighing 165~176 g, were divided into eight groups and treated according to protocol. Testicular histology, stereological parameters, seminal fluid, testosterone, luteinizing hormone, follicle-stimulating hormone, the antioxidants marker malondialdehyde (MDA), and antioxidant glutathione (GSH) were examined. The use of ethanol alone and ethanol + HAART showed extensive degeneration in the seminiferous epithelium, decreased semen quality, disorganized basement membrane and widened, hypocellular interstitium. GSH was significantly decreased in the ethanol alone treated group with no significant effect on testosterone, LH, and MDA levels. Adjuvant treatment with VCO at low dose (2.5 mL/kg/bw) improved sperm motility with a partial restoration of the histopathological alterations. High doses of VCO (5.0 mL/kg/bw) showed greater improvement with respect to sperm counts, increased FSH hormonal and GSH antioxidant levels, and a well-preserved testicular cyto-architecture. © 2018 American Society of Andrology and European Academy of Andrology.

  10. Striatal modulation of BDNF expression using microRNA124a-expressing lentiviral vectors impairs ethanol-induced conditioned-place preference and voluntary alcohol consumption.

    Bahi, Amine; Dreyer, Jean-Luc

    2013-07-01

    Alcohol abuse is a major health, economic and social concern in modern societies, but the exact molecular mechanisms underlying ethanol addiction remain elusive. Recent findings show that small non-coding microRNA (miRNA) signaling contributes to complex behavioral disorders including drug addiction. However, the role of miRNAs in ethanol-induced conditioned-place preference (CPP) and voluntary alcohol consumption has not yet been directly addressed. Here, we assessed the expression profile of miR124a in the dorsal striatum of rats upon ethanol intake. The results show that miR124a was downregulated in the dorso-lateral striatum (DLS) following alcohol drinking. Then, we identified brain-derived neurotrophic factor (BDNF) as a direct target of miR124a. In fact, BDNF mRNA was upregulated following ethanol drinking. We used lentiviral vector (LV) gene transfer technology to further address the role of miR124a and its direct target BDNF in ethanol-induced CPP and alcohol consumption. Results reveal that stereotaxic injection of LV-miR124a in the DLS enhances ethanol-induced CPP as well as voluntary alcohol consumption in a two-bottle choice drinking paradigm. Moreover, miR124a-silencer (LV-siR124a) as well as LV-BDNF infusion in the DLS attenuates ethanol-induced CPP as well as voluntary alcohol consumption. Importantly, LV-miR124a, LV-siR124a and LV-BDNF have no effect on saccharin and quinine intake. Our findings indicate that striatal miR124a and BDNF signaling have crucial roles in alcohol consumption and ethanol conditioned reward. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  11. Alcohol--Induced Polyelectrolyte-Surfactant Complex Coacervate Systems: Characterization and Applications in Enzyme and Protein Extraction

    Nejati Moshtaghin, Mahboubeh

    The focus of this thesis is to achieve a better understanding of the newly discovered surfactant-polyelectrolyte complex coacervate (SPCC) systems induced by fluoroalcohol/acid as well as short chain aliphatic alcohol; and to elucidate their applications in extraction and enrichment of proteins and enzyme. We have discovered that fluoroalcohols and --acids induce complex coacervation and phase separation in the aqueous mixtures of oppositely charged anionic polyelectrolytes; specifically, sodium salts of polyacrylic acid and polymethacrylic acid and cationic surfactant (cetyltrimethylammonium bromide, CTAB) over a broad range of concentrations of mole fractions of the oppositely charged amphiphiles. Accordingly, these new classes of coacervators will significantly broaden the scope and facilitate engineering of new coacervate phases. Toward these goals, we have inspected the formation of surfactant-polyelectrolyte complex coacervates in the presence of fluoroalcohols namely hexafluoroisopropanol (HFIP) and Trifluoroethanol (TFE). Furthermore, the extent of coacervation as a function of concentrations the system components, and charge ratios of the oppositely charged amphiphiles has been investigated. Polyelectrolytes are considered to be milder reagents, as compared to surfactants, regarding proteins denaturation. This highlights the importance of a detailed investigation of the efficiency of our coacervate systems for extraction and preconcentration of proteins and enzymes, especially, when the biological activity of the extracted proteins needs to be maintained based on the objectives mentioned above, the results of the investigations have been organized in four chapters. In Chapter II, the phase behavior of the FA-SPCC will be investigated. The objective is to examine the phase behavior and phase properties with respect to the extent of coacervation in different solution conditions. In particular, the effects of different solution variables such as concentration

  12. Polycyclic aromatic hydrocarbon-induced CYP1B1 activity is suppressed by perillyl alcohol in MCF-7 cells

    Chan, Nelson L.S.; Wang Huan; Wang Yun; Leung, H.Y.; Leung, Lai K.

    2006-01-01

    Perillyl alcohol (POH) is a dietary monoterpene with potential applications in chemoprevention and chemotherapy. Although clinical trials are under way, POH's physiological and pharmacological properties are still unclear. In the present study, the effect of POH on polycyclic aromatic hydrocarbon (PAH)-induced genotoxicity, and the related expression were examined in MCF-7 cells. Exposure to environmental toxicant increases the risk of cancer. Many of these compounds are pro-carcinogens and are biotransformed into their ultimate genotoxic structures by xenobiotic metabolizing enzymes. CYP1A1 and 1B1 are enzymes that catalyze the biotransformation of dimethylbenz[a]anthracene (DMBA). Our data revealed that 0.5 μM of POH was effective in blocking DMBA-DNA binding. Ethoxyresorufin-O-deethylase (EROD) assay indicated that the administration of POH inhibited the DMBA-induced enzyme activity in MCF-7 cells. Enzyme kinetic analysis revealed that POH inhibited CYP1B1 but not CYP1A1 activity. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) assay also demonstrated that the monoterpene reduced CYP1B1 mRNA abundance induced by DMBA. The present study illustrated that POH might inhibit and downregulate CYP1B1, which could protect against PAH-induced carcinogenesis

  13. Turmeric Extract Rescues Ethanol-Induced Developmental Defect in the Zebrafish Model for Fetal Alcohol Spectrum Disorder (FASD).

    Muralidharan, Pooja; Connors, Craig T; Mohammed, Arooj S; Sarmah, Swapnalee; Marrs, Kathleen; Marrs, James A; Chism, Grady W

    2017-09-01

    Prenatal ethanol exposure causes the most frequent preventable birth disorder, fetal alcohol spectrum disorder (FASD). The effect of turmeric extracts in rescuing an ethanol-induced developmental defect using zebrafish as a model was determined. Ethanol-induced oxidative stress is one of the major mechanisms underlying FASD. We hypothesize that antioxidant inducing properties of turmeric may alleviate ethanol-induced defects. Curcuminoid content of the turmeric powder extract (5 mg/mL turmeric in ethanol) was determined by UPLC and found to contain Curcumin (124.1 ± 0.2 μg/mL), Desmethoxycurcumin (43.4 ± 0.1 μg/mL), and Bisdemethoxycurcumin (36.6 ± 0.1 μg/mL). Zebrafish embryos were treated with 100 mM (0.6% v/v) ethanol during gastrulation through organogenesis (2 to 48 h postfertilization (hpf)) and supplemented with turmeric extract to obtain total curcuminoid concentrations of 0, 1.16, 1.72, or 2.32 μM. Turmeric supplementation showed significant rescue of the body length at 72 hpf compared to ethanol-treated embryos. The mechanism underlying the rescue remains to be determined. © 2017 Institute of Food Technologists®.

  14. Glucose-induced glucagon-like Peptide 1 secretion is deficient in patients with non-alcoholic fatty liver disease.

    Christine Bernsmeier

    Full Text Available The incretins glucagon-like peptide-1 (GLP-1 and glucose-dependent insulinotropic polypeptide (GIP are gastrointestinal peptide hormones regulating postprandial insulin release from pancreatic β-cells. GLP-1 agonism is a treatment strategy in Type 2 diabetes and is evaluated in Non-alcoholic fatty liver disease (NAFLD. However, the role of incretins in its pathophysiology is insufficiently understood. Studies in mice suggest improvement of hepatic steatosis by GLP-1 agonism. We determined the secretion of incretins after oral glucose administration in non-diabetic NAFLD patients.N=52 patients (n=16 NAFLD and n=36 Non-alcoholic steatohepatitis (NASH patients and n=50 matched healthy controls were included. Standardized oral glucose tolerance test was performed. Glucose, insulin, glucagon, GLP-1 and GIP plasma levels were measured sequentially for 120 minutes after glucose administration.Glucose induced GLP-1 secretion was significantly decreased in patients compared to controls (p<0.001. In contrast, GIP secretion was unchanged. There was no difference in GLP-1 and GIP secretion between NAFLD and NASH subgroups. All patients were insulin resistant, however HOMA2-IR was highest in the NASH subgroup. Fasting and glucose-induced insulin secretion was higher in NAFLD and NASH compared to controls, while the glucose lowering effect was diminished. Concomitantly, fasting glucagon secretion was significantly elevated in NAFLD and NASH.Glucose-induced GLP-1 secretion is deficient in patients with NAFLD and NASH. GIP secretion is contrarily preserved. Insulin resistance, with hyperinsulinemia and hyperglucagonemia, is present in all patients, and is more severe in NASH compared to NAFLD. These pathophysiologic findings endorse the current evaluation of GLP-1 agonism for the treatment of NAFLD.

  15. Alcohol dehydrogenase accentuates ethanol-induced myocardial dysfunction and mitochondrial damage in mice: role of mitochondrial death pathway.

    Rui Guo

    2010-01-01

    Full Text Available Binge drinking and alcohol toxicity are often associated with myocardial dysfunction possibly due to accumulation of the ethanol metabolite acetaldehyde although the underlying mechanism is unknown. This study was designed to examine the impact of accelerated ethanol metabolism on myocardial contractility, mitochondrial function and apoptosis using a murine model of cardiac-specific overexpression of alcohol dehydrogenase (ADH.ADH and wild-type FVB mice were acutely challenged with ethanol (3 g/kg/d, i.p. for 3 days. Myocardial contractility, mitochondrial damage and apoptosis (death receptor and mitochondrial pathways were examined.Ethanol led to reduced cardiac contractility, enlarged cardiomyocyte, mitochondrial damage and apoptosis, the effects of which were exaggerated by ADH transgene. In particular, ADH exacerbated mitochondrial dysfunction manifested as decreased mitochondrial membrane potential and accumulation of mitochondrial O(2 (*-. Myocardium from ethanol-treated mice displayed enhanced Bax, Caspase-3 and decreased Bcl-2 expression, the effect of which with the exception of Caspase-3 was augmented by ADH. ADH accentuated ethanol-induced increase in the mitochondrial death domain components pro-caspase-9 and cytochrome C in the cytoplasm. Neither ethanol nor ADH affected the expression of ANP, total pro-caspase-9, cytosolic and total pro-caspase-8, TNF-alpha, Fas receptor, Fas L and cytosolic AIF.Taken together, these data suggest that enhanced acetaldehyde production through ADH overexpression following acute ethanol exposure exacerbated ethanol-induced myocardial contractile dysfunction, cardiomyocyte enlargement, mitochondrial damage and apoptosis, indicating a pivotal role of ADH in ethanol-induced cardiac dysfunction possibly through mitochondrial death pathway of apoptosis.

  16. Alcohol dehydrogenase accentuates ethanol-induced myocardial dysfunction and mitochondrial damage in mice: role of mitochondrial death pathway.

    Guo, Rui; Ren, Jun

    2010-01-18

    Binge drinking and alcohol toxicity are often associated with myocardial dysfunction possibly due to accumulation of the ethanol metabolite acetaldehyde although the underlying mechanism is unknown. This study was designed to examine the impact of accelerated ethanol metabolism on myocardial contractility, mitochondrial function and apoptosis using a murine model of cardiac-specific overexpression of alcohol dehydrogenase (ADH). ADH and wild-type FVB mice were acutely challenged with ethanol (3 g/kg/d, i.p.) for 3 days. Myocardial contractility, mitochondrial damage and apoptosis (death receptor and mitochondrial pathways) were examined. Ethanol led to reduced cardiac contractility, enlarged cardiomyocyte, mitochondrial damage and apoptosis, the effects of which were exaggerated by ADH transgene. In particular, ADH exacerbated mitochondrial dysfunction manifested as decreased mitochondrial membrane potential and accumulation of mitochondrial O(2) (*-). Myocardium from ethanol-treated mice displayed enhanced Bax, Caspase-3 and decreased Bcl-2 expression, the effect of which with the exception of Caspase-3 was augmented by ADH. ADH accentuated ethanol-induced increase in the mitochondrial death domain components pro-caspase-9 and cytochrome C in the cytoplasm. Neither ethanol nor ADH affected the expression of ANP, total pro-caspase-9, cytosolic and total pro-caspase-8, TNF-alpha, Fas receptor, Fas L and cytosolic AIF. Taken together, these data suggest that enhanced acetaldehyde production through ADH overexpression following acute ethanol exposure exacerbated ethanol-induced myocardial contractile dysfunction, cardiomyocyte enlargement, mitochondrial damage and apoptosis, indicating a pivotal role of ADH in ethanol-induced cardiac dysfunction possibly through mitochondrial death pathway of apoptosis.

  17. Modulation of Intestinal Barrier and Bacterial Endotoxin Production Contributes to the Beneficial Effect of Nicotinic Acid on Alcohol-Induced Endotoxemia and Hepatic Inflammation in Rats

    Wei Zhong

    2015-10-01

    Full Text Available Alcohol consumption causes nicotinic acid deficiency. The present study was undertaken to determine whether dietary nicotinic acid supplementation provides beneficial effects on alcohol-induced endotoxin signaling and the possible mechanisms at the gut-liver axis. Male Sprague-Dawley rats were pair-fed the Lieber-DeCarli liquid diets containing ethanol or isocaloric maltose dextrin for eight weeks, with or without dietary supplementation with 750 mg/liter nicotinic acid. Chronic alcohol feeding elevated the plasma endotoxin level and activated hepatic endotoxin signaling cascade, which were attenuated by nicotinic acid supplementation. Alcohol consumption remarkably decreased the mRNA levels of claudin-1, claudin-5, and ZO-1 in the distal intestine, whereas nicotinic acid significantly up-regulated these genes. The concentrations of endotoxin, ethanol, and acetaldehyde in the intestinal contents were increased by alcohol exposure, and niacin supplementation reduced the intestinal endotoxin and acetaldehyde levels. Nicotinic acid supplementation upregulated the intestinal genes involved in aldehyde detoxification via transcriptional regulation. These results demonstrate that modulation of the intestinal barrier function and bacterial endotoxin production accounts for the inhibitory effects of nicotinic acid on alcohol-induced endotoxemia and hepatic inflammation.

  18. Unilateral inactivation of the basolateral amygdala attenuates context-induced renewal of Pavlovian-conditioned alcohol-seeking

    Chaudhri, N.; Woods, C. A.; Sahuque, L.L.; Gill, T. M.; Janak, P.H.

    2014-01-01

    Environmental contexts associated with drug use promote craving in humans and drug-seeking in animals. We hypothesized that the basolateral amygdala (BLA) itself, as well as serial connectivity between the basolateral amygdala (BLA) and nucleus accumbens core (NAC core), were required for context-induced renewal of Pavlovian-conditioned alcohol-seeking. Male, Long-Evans rats were trained to discriminate between two conditioned stimuli (CS) - a CS+ that was paired with ethanol (EtOH, 20%, v/v) delivery into a fluid port (0.2 ml/CS+, 3.2 ml/session) and a CS− that was not. Entries into the port during each CS were measured. Next, rats received extinction in a different context where both cues were presented without EtOH. At test, responding to the CS+ and CS− without EtOH was evaluated in the prior training context. Control subjects showed a selective increase in CS+ responding relative to extinction, indicative of renewal. This effect was blocked by pre-test, bilateral inactivation of the BLA using a solution of gamma-amino-butyric-acid receptor agonists (0.1 mM muscimol and 1.0 mM baclofen; M/B; 0.3 µl/side). Renewal was also attenuated following unilateral injections of M/B into the BLA, combined with either M/B, the dopamine D1 receptor antagonist SCH 23390 (0.6 µg/side), or saline infusion in the contralateral NAC core. Hence, unilateral BLA inactivation was sufficient to disrupt renewal, highlighting a critical role for functional activity in the BLA in enabling the reinstatement of alcohol-seeking driven by an alcohol context. PMID:23758059

  19. PROTECTIVE EFFECTS OF HYPOTHALAMIC BETA-ENDORPHIN NEURONS AGAINST ALCOHOL-INDUCED LIVER INJURIES AND LIVER CANCERS IN RAT ANIMAL MODELS

    Murugan, Sengottuvelan; Boyadjieva, Nadka; Sarkar, Dipak K.

    2014-01-01

    Background Recently, retrograde tracing has provided evidence for an influence of hypothalamic β-endorphin (BEP) neurons on the liver, but functions of these neurons are not known. We evaluated the effect of BEP neuronal activation on alcohol-induced liver injury and hepatocellular cancer. Methods Male rats received either BEP neuron transplants or control transplants in the hypothalamus and randomly assigned to feeding alcohol-containing liquid diet or control liquid diet for 8 weeks or to treatment of a carcinogen diethylnitrosamine (DEN). Liver tissues of these animals were analyzed histochemically and biochemically for tissue injuries or cancer. Results Alcohol-feeding increased liver weight and induced several histopathological changes such as prominent microvesicular steatosis and hepatic fibrosis. Alcohol feeding also increased protein levels of triglyceride, hepatic stellate cell activation factors and catecholamines in the liver and endotoxin levels in the plasma. However, these effects of alcohol on the liver were reduced in animals with BEP neuron transplants. BEP neuron transplants also suppressed carcinogen-induced liver histopathologies such as extensive fibrosis, large focus of inflammatory infiltration, hepatocelluar carcinoma, collagen deposition, numbers of preneoplastic foci, levels of hepatic stellate cell activation factors and catecholamines, as well as inflammatory milieu and the levels of NK cell cytotoxic factors in the liver. Conclusion These findings are the first evidence for a role of hypothalamic BEP neurons in influencing liver functions. Additionally, the data identify that BEP neuron transplantation prevents hepatocellular injury and hepatocellular carcinoma formation possibly via influencing the immune function. PMID:25581653

  20. Protective effect of pineapple (Ananas cosmosus peel extract on alcohol-induced oxidative stress in brain tissues of male albino rats

    Ochuko L Erukainure

    2011-03-01

    Full Text Available Objective: To investigate the ability of pineapple peels to protect against alcohol-induced oxidative stress in brain tissues using male albino rat models. Methods: Response surface methodology (RSM was used to design a series of experiments to optimize treatment conditions with the aim of investigating the protective effect of pineapple peel extract on alcohol-induced oxidative stress in brain tissues. Oxidative stress was induced by oral administration of ethanol (20% w/v at a dosage of 5 mL/kg bw. The treatment lasted for 28 days. At the end of the treatment, the rats were fasted overnight and sacrificed by cervical dislocation. Tissue homogenates were used for the assessment of protein concentration, reduced glutathione (GSH content, catalase, and SOD. Results: Alcohol administration caused a significant decrease (P>0.05 in GSH level in the group which was only fed alcohol. Treatment with pineapple peel extracts caused increase in GSH level in alcohol fed groups. No significant difference (P<0.05 was observed in SOD levels of the negative control and group fed on only pineapple peel extract. Elevated level of catalase was observed in the negative control but pineapple peel extract significantly reduced the levels. Conclusions: This study indicates the protective effect of pineapple peel against alcoholinduced oxidative stress in brain tissues.

  1. Effects of Puerariae Radix Extract on Endotoxin Receptors and TNF-α Expression Induced by Gut-Derived Endotoxin in Chronic Alcoholic Liver Injury

    Jing-Hua Peng

    2012-01-01

    Full Text Available Kudzu (Pueraria lobata is one of the earliest medicinal plants used to treat alcohol abuse in traditional Chinese medicine for more than a millennium. However, little is known about its effects on chronic alcoholic liver injury. Therefore, the present study observed the effects of puerariae radix extract (RPE on chronic alcoholic liver injury as well as Kupffer cells (KCs activation to release tumor necrosis factor alpha (TNF-α induced by gut-derived endotoxin in rats and macrophage cell line. RPE was observed to alleviate the pathological changes and lipids deposition in liver tissues as well as the serum alanine aminotransferase (ALT, aspartate aminotransferase (AST, and hepatic gamma-glutamyl transpeptidase (GGT activity. Meanwhile, RPE inhibited KCs activation and subsequent hepatic TNF-α expression and downregulated the protein expression of endotoxin receptors, lipopolysaccharide binding protein (LBP, CD14, Toll-like receptor (TLR 2, and TLR4 in chronic alcohol intake rats. Furthermore, an in vitro study showed that RPE inhibited the expression of TNF-α and endotoxin receptors, CD14 and TLR4, induced by LPS in RAW264.7 cells. In summary, this study demonstrated that RPE mitigated liver damage and lipid deposition induced by chronic alcohol intake in rats, as well as TNF-α release, protein expression of endotoxin receptors in vivo or in vitro.

  2. Neutrophil depletion improves diet-induced non-alcoholic fatty liver disease in mice.

    Ou, Rongying; Liu, Jia; Lv, Mingfen; Wang, Jingying; Wang, Jinmeng; Zhu, Li; Zhao, Liang; Xu, Yunsheng

    2017-07-01

    Non-alcoholic fatty liver disease is highly associated with morbidity and mortality in population. Although studies have already demonstrated that the immune response plays a pivotal role in the development of non-alcoholic fatty liver disease, the comprehensive regulation is unclear. Therefore, present study was carried out to investigate the non-alcoholic fatty liver disease development under neutrophil depletion. To achieve the aim of the study, C57BL/6 J mice were fed with high fat diet for 6 weeks before treated with neutrophil deplete antibody 1A8 or isotype control (200 μg/ mouse every week) for another 4 weeks. Treated with 1A8 antibody, obese mice exhibited better whole body metabolic parameters, including reduction of body weight gain and fasting blood glucose levels. Neutrophil depletion also effectively reduced hepatic structural disorders, dysfunction and lipid accumulation. Lipid β-oxidative markers, phosphorylated-AMP-activated protein kinase α and phosphorylated-acetyl-CoA carboxylase levels were increased in 1A8 antibody-treated obese mouse group. The mitochondrial number and function were also reversed after 1A8 antibody treatment, including increased mitochondrial number, reduced lipid oxidative damage and enhanced mitochondrial activity. Furthermore, the expression of inflammatory cytokines, tumor necrosis factor-α, interleukin-6, and monocyte chemoattractant protein-1 were obviously reduced after neutrophil depletion, accompanied with decreased F4/80 mRNA level and macrophage percentage in liver. The decreased NF-κB signaling activity was also involved in the beneficial effect of neutrophil depletion. Taken together, neutrophil depletion could attenuate metabolic syndromes and hepatic dysfunction.

  3. The enhanced alcohol sensing response of multiwalled carbon nanotube networks induced by alkyl diamine treatment

    Benlikaya, R.; Slobodian, P.; Říha, Pavel; Olejník, R.

    2014-01-01

    Roč. 201, October (2014), s. 122-130 ISSN 0925-4005 R&D Projects: GA MŠk(CZ) CZ.1.07/2.3.00/20.0104 Grant - others:UTB Zlín(CZ) IGA/FT/2013/018; GA MŠk(CZ) ED2.1.00/03.0111 Institutional research plan: CEZ:AV0Z20600510 Institutional support: RVO:67985874 Keywords : carbon nanotubes * multiwalled carbon nanotube networks * vapor sensing * linear alcohols * alkyl diamine treatment Subject RIV: BK - Fluid Dynamics Impact factor: 4.097, year: 2014

  4. The enhanced alcohol sensing response of multiwalled carbon nanotube networks induced by alkyl diamine treatment

    Benlikaya, R.; Slobodian, P.; Říha, Pavel; Olejník, R.

    2014-01-01

    Roč. 201, October (2014), s. 122-130 ISSN 0925-4005 R&D Projects: GA MŠk(CZ) CZ.1.07/2.3.00/20.0104 Grant - others:UTB Zlín(CZ) IGA/FT/2013/018; GA MŠk(CZ) ED2.1.00/03.0111 Institutional research plan: CEZ:AV0Z20600510 Institutional support: RVO:67985874 Keywords : carbon nanotubes * multiwalled carbon nanotube networks * vapor sensing * linear alcohol s * alkyl diamine treatment Subject RIV: BK - Fluid Dynamics Impact factor: 4.097, year: 2014

  5. Alcohol-Induced Physiological Displacements and Their Effects on Flight-Related Functions

    1982-03-01

    measured height and weight (6). One part bourbon per two parts of Coca Cola were mixed, divided equally into three drinks and drunk at an even rate over a...temporary protection against a plasma volume decrease (21). In our study, the imbibed volume of alcohol plus Coca Cola (about 350-550 ml) temporarily...amE E T Office of Aviation Medicine MAY 2 7 1982 Washington, D.C. 20591A~A C.-, t(Jin NOTICE This document is disseminated under the sponsorship of

  6. Effects of Chronic Alcohol Exposure on the Modulation of Ischemia-Induced Glutamate Release via Cannabinoid Receptors in the Dorsal Hippocampus.

    Zheng, Lei; Wu, Xiaoda; Dong, Xiao; Ding, Xinli; Song, Cunfeng

    2015-10-01

    Chronic alcohol consumption is a critical contributing factor to ischemic stroke, as it enhances ischemia-induced glutamate release, leading to more severe excitotoxicity and brain damage. But the neural mechanisms underlying this phenomenon are poorly understood. We evaluated the effects of chronic alcohol exposure on the modulation of ischemia-induced glutamate release via CB1 and CB2 cannabinoid receptors during middle cerebral artery occlusion, using in vivo microdialysis coupled with high-performance liquid chromatography, in alcohol-naïve rats or rats after 1 or 30 days of withdrawal from chronic ethanol intake (6% v/v for 14 days). Intra-dorsal hippocampus (DH) infusions of ACEA or JWH133, selective CB1 or CB2 receptor agonists, respectively, decreased glutamate release in the DH in alcohol-naïve rats in a dose-dependent manner. Such an effect was reversed by co-infusions of SR141716A or AM630, selective CB1 or CB2 receptor antagonists, respectively. After 30 days, but not 1 day of withdrawal, ischemia induced an enhancement in glutamate release in the DH, as compared with non-alcohol-treated control group. Intra-DH infusions of JWH133, but not ACEA, inhibited ischemia-induced glutamate release in the DH after 30 days of withdrawal. Finally, 1 day of withdrawal did not alter the protein level of CB1 or CB2 receptors in the DH, as compared to non-alcohol-treated control rats. Whereas 30 days of withdrawal robustly decreased the protein level of CB1 receptors, but failed to alter the protein level of CB2 receptors, in the DH, as compared to non-alcohol-treated control rats. Together, these findings suggest that loss of expression/function of CB1 receptors, but not CB2 receptors in the DH, is correlated with the enhancement of ischemia-induced glutamate release after prolonged alcohol withdrawal. Copyright © 2015 by the Research Society on Alcoholism.

  7. Unique Behavioral and Neurochemical Effects Induced by Repeated Adolescent Consumption of Caffeine-Mixed Alcohol in C57BL/6 Mice.

    Meridith T Robins

    Full Text Available The number of highly caffeinated products has increased dramatically in the past few years. Among these products, highly caffeinated energy drinks are the most heavily advertised and purchased, which has resulted in increased incidences of co-consumption of energy drinks with alcohol. Despite the growing number of adolescents and young adults reporting caffeine-mixed alcohol use, knowledge of the potential consequences associated with co-consumption has been limited to survey-based results and in-laboratory human behavioral testing. Here, we investigate the effect of repeated adolescent (post-natal days P35-61 exposure to caffeine-mixed alcohol in C57BL/6 mice on common drug-related behaviors such as locomotor sensitivity, drug reward and cross-sensitivity, and natural reward. To determine changes in neurological activity resulting from adolescent exposure, we monitored changes in expression of the transcription factor ΔFosB in the dopaminergic reward pathway as a sign of long-term increases in neuronal activity. Repeated adolescent exposure to caffeine-mixed alcohol exposure induced significant locomotor sensitization, desensitized cocaine conditioned place preference, decreased cocaine locomotor cross-sensitivity, and increased natural reward consumption. We also observed increased accumulation of ΔFosB in the nucleus accumbens following repeated adolescent caffeine-mixed alcohol exposure compared to alcohol or caffeine alone. Using our exposure model, we found that repeated exposure to caffeine-mixed alcohol during adolescence causes unique behavioral and neurochemical effects not observed in mice exposed to caffeine or alcohol alone. Based on similar findings for different substances of abuse, it is possible that repeated exposure to caffeine-mixed alcohol during adolescence could potentially alter or escalate future substance abuse as means to compensate for these behavioral and neurochemical alterations.

  8. Prevention of congenital defects induced by prenatal alcohol exposure (Conference Presentation)

    Sheehan, Megan M.; Karunamuni, Ganga; Pedersen, Cameron J.; Gu, Shi; Doughman, Yong Qiu; Jenkins, Michael W.; Watanabe, Michiko; Rollins, Andrew M.

    2017-02-01

    Nearly 2 million women in the United States alone are at risk for an alcohol-exposed pregnancy, including more than 600,000 who binge drink. Even low levels of prenatal alcohol exposure (PAE) can lead to a variety of birth defects, including craniofacial and neurodevelopmental defects, as well as increased risk of miscarriages and stillbirths. Studies have also shown an interaction between drinking while pregnant and an increase in congenital heart defects (CHD), including atrioventricular septal defects and other malformations. We have previously established a quail model of PAE, modeling a single binge drinking episode in the third week of a woman's pregnancy. Using optical coherence tomography (OCT), we quantified intraventricular septum thickness, great vessel diameters, and atrioventricular valve volumes. Early-stage ethanol-exposed embryos had smaller cardiac cushions (valve precursors) and increased retrograde flow, while late-stage embryos presented with gross head/body defects, and exhibited smaller atrio-ventricular (AV) valves, interventricular septum, and aortic vessels. We previously showed that supplementation with the methyl donor betaine reduced gross defects, improved survival rates, and prevented cardiac defects. Here we show that these preventative effects are also observed with folate (another methyl donor) supplementation. Folate also appears to normalize retrograde flow levels which are elevated by ethanol exposure. Finally, preliminary findings have shown that glutathione, a crucial antioxidant, is noticeably effective at improving survival rates and minimizing gross defects in ethanol-exposed embryos. Current investigations will examine the impact of glutathione supplementation on PAE-related CHDs.

  9. Carbon Source-Dependent Inducible Metabolism of Veratryl Alcohol and Ferulic Acid in Pseudomonas putida CSV86

    Mohan, Karishma

    2017-01-01

    ABSTRACT Pseudomonas putida CSV86 degrades lignin-derived metabolic intermediates, viz., veratryl alcohol, ferulic acid, vanillin, and vanillic acid, as the sole sources of carbon and energy. Strain CSV86 also degraded lignin sulfonate. Cell respiration, enzyme activity, biotransformation, and high-pressure liquid chromatography (HPLC) analyses suggest that veratryl alcohol and ferulic acid are metabolized to vanillic acid by two distinct carbon source-dependent inducible pathways. Vanillic acid was further metabolized to protocatechuic acid and entered the central carbon pathway via the β-ketoadipate route after ortho ring cleavage. Genes encoding putative enzymes involved in the degradation were found to be present at fer, ver, and van loci. The transcriptional analysis suggests a carbon source-dependent cotranscription of these loci, substantiating the metabolic studies. Biochemical and quantitative real-time (qRT)-PCR studies revealed the presence of two distinct O-demethylases, viz., VerAB and VanAB, involved in the oxidative demethylation of veratric acid and vanillic acid, respectively. This report describes the various steps involved in metabolizing lignin-derived aromatic compounds at the biochemical level and identifies the genes involved in degrading veratric acid and the arrangement of phenylpropanoid metabolic genes as three distinct inducible transcription units/operons. This study provides insight into the bacterial degradation of lignin-derived aromatics and the potential of P. putida CSV86 as a suitable candidate for producing valuable products. IMPORTANCE Pseudomonas putida CSV86 metabolizes lignin and its metabolic intermediates as a carbon source. Strain CSV86 displays a unique property of preferential utilization of aromatics, including for phenylpropanoids over glucose. This report unravels veratryl alcohol metabolism and genes encoding veratric acid O-demethylase, hitherto unknown in pseudomonads, thereby providing new insight into the

  10. CORONA-INDUCED PHOTOXIDATION OF ALCOHOLS AND HYDROCARBONS OVER TIO2 IN THE ABSENCE OF A UV LIGHT SOURCE - A NOVEL AND ENVIRONMENTALLY FRIENDLY METHOD FOR OXIDATION

    Corona-induced photooxidation is a novel oxidation methodology for the efficient oxidation of alcohols and hydrocarbons utilizing the advantage of both the high oxidizing power of ozone formed in the reactor as well as the photooxidation capability of the UV light generated durin...

  11. Preparation and physical properties of enhanced radiation induced crosslinking of ethylene-vinyl alcohol copolymer (EVOH)

    Deng Pengyang; Liu Meihua; Zhang Wanxi; Sun Jiazhen

    2007-01-01

    Preparation and physical properties of ethylene-vinyl alcohol copolymer (EVOH) crosslinked by enhanced radiation have been studied through various methods. It was found that the most effective agent for irradiation-crosslinking was triallyl isocyanurate (TAIC) among four kinds of polyfunctional monomers. Gel content (65.6%) was formed for EVOH-44 (content of ethylene is 44 mol%) at 200 kGy with 5% TAIC, but for EVOH-32 (content of ethylene is 32 mol%), only 37.4% gel content was formed under the same conditions. This result showed that the more the content of ethylene units comprised in EVOH, the easier the chemical bonds could be formed between different molecular chains. Tensile strength and elastic modulus increased after crosslinking at high test temperature and elongation at break decreased at the same time. Hygroscopicity of EVOH showed noticeable decrease after enhancement radiation-crosslinking

  12. Saturday night palsy or Sunday morning hangover? A case report of alcohol-induced Crush Syndrome.

    Devitt, Brian M

    2011-01-01

    Saturday night palsy is a colloquial term given to brachial plexus injuries of the arm resulting from stretching or direct pressure against a firm object, often after alcohol or drug consumption. In most circumstances, this condition gives rise to a temporary plexopathy, which generally resolves. However, if the compression is severe and prolonged, a more grave form of this condition known as \\'Crush Syndrome\\' may occur. Skeletal muscle injury, brought about by protracted immobilization, leads to muscle decay, causing rhabdomyolysis, which may in turn precipitate acute renal failure. This condition is potentially fatal and has an extremely high morbidity. The case presented below demonstrates the drastic consequences that can result following an episode of \\'binge\\' drinking in a young man. What is most concerning is that this trend is increasing across society and cases like this may not be as rare in the future.

  13. Prevention of congenital defects induced by prenatal alcohol exposure (Conference Presentation)

    Sheehan, Megan M.; Karunamuni, Ganga; Pedersen, Cameron J.; Gu, Shi; Doughman, Yong Qiu; Jenkins, Michael W.; Watanabe, Michiko; Rollins, Andrew M.

    2017-02-01

    Over 500,000 women per year in the United States drink during pregnancy, and 1 in 5 of this population also binge drink. Up to 40% of live-born children with prenatal alcohol exposure (PAE) present with congenital heart defects (CHDs) including life-threatening outflow and valvuloseptal anomalies. Previously we established a PAE model in the avian embryo and used optical coherence tomography (OCT) imaging to assay looping-stage (early) cardiac function/structure and septation-stage (late) cardiac defects. Early-stage ethanol-exposed embryos had smaller cardiac cushions (valve precursors) and increased retrograde flow, while late-stage embryos presented with gross head/body defects, and exhibited smaller atrio-ventricular (AV) valves, interventricular septae, and aortic vessels. However, supplementation with the methyl donor betaine reduced gross defects, prevented cardiac defects such as ventricular septal defects and abnormal AV valves, and normalized cardiac parameters. Immunofluorescent staining for 5-methylcytosine in transverse embryo sections also revealed that DNA methylation levels were reduced by ethanol but normalized by co-administration of betaine. Furthermore, supplementation with folate, another methyl donor, in the PAE model appeared to normalize retrograde flow levels which are typically elevated by ethanol exposure. Studies are underway to correlate retrograde flow numbers for folate with associated cushion volumes. Finally, preliminary findings have revealed that glutathione, a key endogenous antioxidant which also regulates methyl group donation, is particularly effective in improving alcohol-impacted survival and gross defect rates. Current investigations will determine whether glutathione has any positive effect on PAE-related CHDs. Our studies could have significant implications for public health, especially related to prenatal nutrition recommendations.

  14. Infrared laser induced organic reactions. 2. Laser vs. thermal inducment of unimolecular and hydrogen bromide catalyzed bimolecular dehydration of alcohols

    Danen, W.C.

    1979-01-01

    It has been demonstrated that a mixture of reactant molecules can be induced by pulsed infrared laser radiation to react via a route which is totally different from the pathway resulting from heating the mixture at 300 0 C. The high-energy unimolecular elimination of H 2 O from ethanol in the presence of 2-propanol and HBr can be selectively induced with a pulsed CO 2 laser in preference to either a lower energy bimolecular HBr-catalyzed dehydration or the more facile dehydration of 2-propanol. Heating the mixture resulted in the almost exclusive reaction of 2-propanol to produce propylene. It was demonstrated that the bimolecular ethanol + HBr reaction cannot be effectively induced by the infrared laser radiation as evidenced by the detrimental effect on the yield of ethylene as the HBr pressure was increased. The selective, nonthermal inducement of H 2 O elimination from vibrationally excited ethanol in the presence of 2-propanol required relatively low reactant pressures. At higher pressures intermolecular V--V energy transfer allowed the thermally more facile dehydration from 2-propanol to become the predominant reaction channel

  15. Stress-induced change in serum BDNF is related to quantitative family history of alcohol use disorder and age at first alcohol use.

    Sharma, Shobhit; Graham, Reiko; Rohde, Rodney; Ceballos, Natalie A

    2017-02-01

    Previous research in animal models suggests that brain-derived neurotrophic factor (BDNF) is involved in stress-modulated alcohol consumption. However, relatively few studies have investigated this issue in humans, and results of existing studies have been heterogeneous. The primary aim of the current study was to examine the within-subjects effect of acute stress (timed math plus cold pressor) on serum BDNF levels (ΔBDNF: post- minus pre-stress) in healthy social drinkers (N=68, 20 male). A secondary aim was to explore which heritable and environmental factors in our limited sample might exert the greatest influences on ΔBDNF. Importantly, presence versus absence of the BDNF Val 66 Met polymorphism (rs6265), which has often been discounted in studies of human serum BDNF, was included as a between-subjects control variable in all statistical analyses. Our results indicated that acute stress decreased serum BDNF. Further, multiple regression analyses revealed that quantitative family history of alcohol use disorder (qFH) and age at first alcohol use together accounted for 15% of the variance in ΔBDNF. Thus, the influences of qFH and age at first alcohol use may explain some of the heterogeneity that exists in previous studies of human serum BDNF. These results parallel findings in animal models and suggest that stress-related changes in serum BDNF are influenced by both heritable (qFH) and environmental (early alcohol consumption) factors. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Alcohol decreases baseline brain glucose metabolism more in heavy drinkers than controls but has no effect on stimulation-induced metabolic increases.

    Volkow, Nora D; Wang, Gene-Jack; Shokri Kojori, Ehsan; Fowler, Joanna S; Benveniste, Helene; Tomasi, Dardo

    2015-02-18

    During alcohol intoxication, the human brain increases metabolism of acetate and decreases metabolism of glucose as energy substrate. Here we hypothesized that chronic heavy drinking facilitates this energy substrate shift both for baseline and stimulation conditions. To test this hypothesis, we compared the effects of alcohol intoxication (0.75 g/kg alcohol vs placebo) on brain glucose metabolism during video stimulation (VS) versus when given with no stimulation (NS), in 25 heavy drinkers (HDs) and 23 healthy controls, each of whom underwent four PET-(18)FDG scans. We showed that resting whole-brain glucose metabolism (placebo-NS) was lower in HD than controls (13%, p = 0.04); that alcohol (compared with placebo) decreased metabolism more in HD (20 ± 13%) than controls (9 ± 11%, p = 0.005) and in proportion to daily alcohol consumption (r = 0.36, p = 0.01) but found that alcohol did not reduce the metabolic increases in visual cortex from VS in either group. Instead, VS reduced alcohol-induced decreases in whole-brain glucose metabolism (10 ± 12%) compared with NS in both groups (15 ± 13%, p = 0.04), consistent with stimulation-related glucose metabolism enhancement. These findings corroborate our hypothesis that heavy alcohol consumption facilitates use of alternative energy substrates (i.e., acetate) for resting activity during intoxication, which might persist through early sobriety, but indicate that glucose is still favored as energy substrate during brain stimulation. Our findings are consistent with reduced reliance on glucose as the main energy substrate for resting brain metabolism during intoxication (presumably shifting to acetate or other ketones) and a priming of this shift in HDs, which might make them vulnerable to energy deficits during withdrawal. Copyright © 2015 the authors 0270-6474/15/353248-08$15.00/0.

  17. Alcohol decreases baseline brain glucose metabolism more in heavy drinkers than controls but has no effect on stimulation-induced metabolic increases

    Volkow, Nora D.; Fowler, Joanna S.; Wang, Gene-Jack; Kojori, Eshan Shokri; Benveniste, Helene; Tomasi, Dardo

    2015-01-01

    During alcohol intoxication the human brain increases metabolism of acetate and decreases metabolism of glucose as energy substrate. Here we hypothesized that chronic heavy drinking facilitates this energy substrate shift both for baseline and stimulation conditions. To test this hypothesis we compared the effects of alcohol intoxication (0.75g/kg alcohol versus placebo) on brain glucose metabolism during video-stimulation (VS) versus when given with no-stimulation (NS), in 25 heavy drinkers (HD) and 23 healthy controls each of whom underwent four PET- 18 FDG scans. We showed that resting whole-brain glucose metabolism (placebo-NS) was lower in HD than controls (13%, p=0.04); that alcohol (compared to placebo) decreased metabolism more in HD (20±13%) than controls (9±11%, p=0.005) and in proportion to daily alcohol consumption (r=0.36, p=0.01) but found that alcohol did not reduce the metabolic increases in visual cortex from VS in either group. Instead, VS reduced alcohol-induced decreases in whole-brain glucose metabolism (10±12%) compared to NS in both groups (15±13%, p=0.04), consistent with stimulation-related glucose metabolism enhancement. These findings corroborate our hypothesis that heavy alcohol consumption facilitates use of alternative energy substrates (i.e. acetate) for resting activity during intoxication, which might persist through early sobriety, but indicate that glucose is still favored as energy substrate during brain stimulation. Our findings are consistent with reduced reliance on glucose as the main energy substrate for resting brain metabolism during intoxication (presumably shifting to acetate or other ketones) and a priming of this shift in heavy drinkers, which might make them vulnerable to energy deficits during withdrawal

  18. An experimental study on effect of antioxidant vitamin E in stress and alcohol induced changes in male fertility in albino rats.

    Sanghishetti Vijay Prasad, Nayak BB, Ghongane BB, Raul AR, Vijay Kumar AN, Mutalik MM, Kapure NL.

    2012-09-01

    Full Text Available Introduction: Physical and Psychological stresses are believed to reduce sexual functions, resulting fromneurotransmission changes in various erectile response pathways and reduced blood flow in genital organs.Intake of alcohol depends on numerous genetic and environmental factors. Stress has long been thought to influence the alcohol drinking in humans. Forced swimming in laboratory animals has been widely used as a model of stress to study the physiological changes and the capacity of the organism in response to stress. Aim: 1. To assess the effect of forced swimming stress on seminal fluid profile, Serum testosterone level, Testicular lipid peroxidation levels. 2. To assess the effect of Vitamin E on stress induced changes. Method: Adult male albino rats weighing 200 – 220 g, aged 12-15 weeks were used in this study. The animals were randomly divided into four groups of 6 animals each. Group1 (control received distilled water, Group 2 (Forced Swimming Stress received distilled water Group 3: subjected to Forced Swimming stress with 20% alcohol intake p.o. Group 4: Swimming stress with 20% alcohol treated with Vitamin E(200mg/kg/day orally. The following parameters were studied in all groups 1. Body weight. 2. Sperm count Motility and Life /death Ratio (SLDR. 3. Serum Testosterone 4. Testicular Malondialdehyde level (MDA. Results: Forced swimming stress caused loss in body wt, reduction in sperm count, motility and SLDR in sperm analysis, reduction in serum testosterone and increase testicular MDA levels compared to control. All the changes were statistically significant. When alcohol was added along with forced swimming it caused further loss in body wt, sperm count, motility and SLDR, serum testosterone level and slightly further increase in MDA levels. These observations were also statistically significant. In case of group IV in which Vitamin E was administered long with stress with alcohol it showed a trend of reversal phenomenon of

  19. Coenzyme Q Metabolism Is Disturbed in High Fat Diet-Induced Non Alcoholic Fatty Liver Disease in Rats

    Kathleen M Botham

    2012-02-01

    Full Text Available Oxidative stress is believed to be a major contributory factor in the development of non alcoholic fatty liver disease (NAFLD, the most common liver disorder worldwide. In this study, the effects of high fat diet-induced NAFLD on Coenzyme Q (CoQ metabolism and plasma oxidative stress markers in rats were investigated. Rats were fed a standard low fat diet (control or a high fat diet (57% metabolizable energy as fat for 18 weeks. The concentrations of total (reduced + oxidized CoQ9 were increased by > 2 fold in the plasma of animals fed the high fat diet, while those of total CoQ10 were unchanged. Reduced CoQ levels were raised, but oxidized CoQ levels were not, thus the proportion in the reduced form was increased by about 75%. A higher percentage of plasma CoQ9 as compared to CoQ10 was in the reduced form in both control and high fat fed rats. Plasma protein thiol (SH levels were decreased in the high fat-fed rats as compared to the control group, but concentrations of lipid hydroperoxides and low density lipoprotein (LDL conjugated dienes were unchanged. These results indicate that high fat diet-induced NAFLD in rats is associated with altered CoQ metabolism and increased protein, but not lipid, oxidative stress.

  20. Deficiency of insulin-like growth factor 1 reduces vulnerability to chronic alcohol intake-induced cardiomyocyte mechanical dysfunction: role of AMPK.

    Ge, Wei; Li, Qun; Turdi, Subat; Wang, Xiao-Ming; Ren, Jun

    2011-08-01

    Circulating insulin-like growth factor I (IGF-1) levels are closely associated with cardiac performance although the role of IGF-1 in alcoholic cardiac dysfunction is unknown. This study was designed to evaluate the impact of severe liver IGF-1 deficiency (LID) on chronic alcohol-induced cardiomyocyte contractile and intracellular Ca(2+) dysfunction. Adult male C57 and LID mice were placed on a 4% alcohol diet for 15 weeks. Cardiomyocyte contractile and intracellular Ca(2+) properties were evaluated including peak shortening (PS), maximal velocity of shortening/relengthening (±dL/dt), time-to-relengthening (TR(90) ), change in fura-fluorescence intensity (ΔFFI) and intracellular Ca(2+) decay. Levels of apoptotic regulators caspase-3, Bcl-2 and c-Jun NH2-terminal kinase (JNK), the ethanol metabolizing enzyme mitochondrial aldehyde dehydrogenase (ALDH2), as well as the cellular fuel gauge AMP-activated protein kinase (AMPK) were evaluated. Chronic alcohol intake enlarged myocyte cross-sectional area, reduced PS, ± dL/dt and ΔFFI as well as prolonged TR(90) and intracellular Ca(2+) decay, the effect of which was greatly attenuated by IGF-1 deficiency. The beneficial effect of LID against alcoholic cardiac mechanical defect was ablated by IGF-1 replenishment. Alcohol intake increased caspase-3 activity/expression although it down-regulated Bcl-2, ALDH2 and pAMPK without affecting JNK and AMPK. IGF-1 deficiency attenuated alcoholism-induced responses in all these proteins with the exception of Bcl-2. In addition, the AMPK agonist 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside abrogated short-term ethanol incubation-elicited cardiac mechanical dysfunction. Taken together, these data suggested that IGF-1 deficiency may reduce the sensitivity to ethanol-induced myocardial mechanical dysfunction. Our data further depicted a likely role of Caspase-3, ALDH2 and AMPK activation in IGF-1 deficiency induced 'desensitization' of alcoholic cardiomyopathy. © 2011 The

  1. Efficacy of curcumin to reduce hepatic damage induced by alcohol and thermally treated oil in rats

    Nasr A.M.N. El-Deen

    2010-03-01

    Full Text Available The authors investigated the effect of curcumin on markers of oxidative stress and liver damage in rats that chronically ingested alcohol and heated oil. Nine groups of ten Wistar male rats received combinations of curcumin 100 mg/kg body weight daily, ethanol 5 mg/kg, 15% dietary sunflower oil and 15% heated sunflower oil for 12 weeks. Serum and liver tissue were collected. Groups 4-6, which had received compounds causing oxidative stress, showed increased serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin, cholesterol, triglycerides, low density lipoprotein, very low density lipoprotein and reduced high density lipoprotein, protein and albumin, compared with the controls. Reductions were observed in glutathione peroxidase and reductase gene expression, superoxide dismutase activity, glutathione peroxidase activity, glutathione reductase activity, reduced glutathione concentration and catalase enzyme activity. Groups 7, 8 and 9 which received curcumin with heated oil, ethanol or both, showed lower elevations in serum and oxidative damage markers compared with the corresponding non-curcumin treated groups.It can be concluded that curcumin reduces markers of liver damage in rats treated with heated sunflower oil or ethanol.

  2. Yeast Extract Promotes Cell Growth and Induces Production of Polyvinyl Alcohol-Degrading Enzymes

    Min Li

    2011-01-01

    Full Text Available Polyvinyl alcohol-degrading enzymes (PVAases have a great potential in bio-desizing processes for its low environmental impact and low energy consumption. In this study, the effect of yeast extract on PVAases production was investigated. A strategy of four-point yeast extract addition was developed and applied to maximize cell growth and PVAases production. As a result, the maximum dry cell weight achieved was 1.48 g/L and the corresponding PVAases activity was 2.99 U/mL, which are 46.5% and 176.8% higher than the control, respectively. Applying this strategy in a 7 L fermentor increased PVAases activity to 3.41 U/mL. Three amino acids (glycine, serine, and tyrosine in yeast extract play a central role in the production of PVAases. These results suggest that the new strategy of four-point yeast extract addition could benefit PVAases production.

  3. Physical changes on the radiation and heat induced poly(Vinyl alcohol) fibers

    Nho, Young Chang; Park, Kyung Ran; Park, Jong Seok; Lim, Youn Mook; Kang, Phil Hyun [Research Division for Industry and Environment, Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2016-11-15

    Poly(vinyl alcohol) (PVA) has high tensile strength and flexibility as well as oxygen barrier properties. The water, which acts as a plasticizer, reduces the tensile strength of PVA and swells PVA as well. It needs to have high water-resistant depending on its applications, especially for the use as tire cords. The aim of this work was to investigate the effect of the annealing temperature and radiation on the Gel content and tensile strength of PVA fbers. For this purpose, gel fraction and tensile strength were determined and analyzed. Annealing was performed in the temperature range of 120-180℃ for 10 min. PVA fbers were irradiated by using a conventional electron beam irradiation at a radiation dose of 50⁓200 kGy, at a dose of 10 kGy/pass at room temperature (acceleration voltage of 1 MeV). Annealing markedly increased the Gel content and the tensile strength of PVA fbers. However irradiation lowered the Gel content and the tensile strength of PVA fbers because they were degraded easily by radiation.

  4. ESR Study of the polyvinyl alcohol gamma-ray induced free-radicals

    Rosas S, E.

    1994-01-01

    This work reports the findings of the molecular weight effect on the electron spin resonance saturation curve of the gamma-ray irradiated polyvinyl alcohol, G-RIPVA. It has been noted that Pva of a lower molecular weight, between 13,000-23,000, show some noticeable differences in the electron spin resonance, ESR, response as a function of the gamma-ray dose in the 1-100 k Gy range than the one reported in the literature with molecular weight of 108,000. Results show a linear response in the log-log plot of the dose vs ESR signal intensity for samples based on G-RIPVA of the lower molecular weight as contrasted with the non-linear ESR response of G-RIPVA of higher molecular weight in the above named dose range. Such a result has been assumed to arise from the shorter molecular chains for the case of the lower molecular weight samples making this to increase the production of Pva free radicals with respect to the absorbed studied doses. Also, a discussion on the nature and stability of the Pva free radicals will be given. (Author)

  5. Social pressure-induced craving in patients with alcohol dependence: application of virtual reality to coping skill training.

    Lee, Jung Suk; Namkoong, Kee; Ku, Jeonghun; Cho, Sangwoo; Park, Ji Yeon; Choi, You Kyong; Kim, Jae-Jin; Kim, In Young; Kim, Sun I; Jung, Young-Chul

    2008-12-01

    This study was conducted to assess the interaction between alcohol cues and social pressure in the induction of alcohol craving. Fourteen male patients with alcohol dependence and 14 age-matched social drinkers completed a virtual reality coping skill training program composed of four blocks according to the presence of alcohol cues (x2) and social pressure (x2). Before and after each block, the craving levels were measured using a visual analogue scale. Patients with alcohol dependence reported extremely high levels of craving immediately upon exposure to a virtual environment with alcohol cues, regardless of social pressure. In contrast, the craving levels of social drinkers were influenced by social pressure from virtual avatars. Our findings imply that an alcohol cue-laden environment should interfere with the ability to use coping skills against social pressure in real-life situations.

  6. Effect of Prazosin and Naltrexone on Script Induced Alcohol Craving in Veterans with Alcohol Use Disorders with and without Co-occurring PTSD

    2017-01-01

    and each is postulated to be mediated by different neurological substrates. The neural networks postulated to subserve reward and relief craving...noradrenergic system with craving-related brain systems, blocking α1 receptors with the noradrenergic antagonist, prazosin, theoretically has the...to evaluate whether specific individual characteristics, including PTSD status, moderate medication response. 15. SUBJECT TERMS Alcohol Drinking

  7. ALCOHOL AND HEART RHYTHM DISORDERS

    A. O. Yusupova

    2015-01-01

    Full Text Available Alcohol abuse and particularly extension of alcohol consumption in alcohol diseas increases the risk of cardiac arrhythmias development and aggravates existing arrhythmias. Patients do not always receive the necessary specific treatment due to lack of detection of the ethanol genesis of these arrhythmias. Management of patients with alcohol abuse and alcohol dependence, including its cardiac complications among other cardiac arrhythmias should use both antiarrhythmic and anti-alcohol drugs and antidepressants. Such issues as diagnosis and management of patients with alcohol-induced cardiac arrhythmias are presented.

  8. Clarification as to why alcoholic beverages have the ability to induce superconductivity in Fe1+dTe1−xSx

    Deguchi, K; Hara, H; Kawasaki, Y; Demura, S; Watanabe, T; Denholme, S J; Okazaki, H; Ozaki, T; Yamaguchi, T; Takeya, H; Takano, Y; Sato, D; Sugimoto, M; Soga, T; Tomita, M

    2012-01-01

    To elucidate the mechanism as to why alcoholic beverages can induce superconductivity in Fe 1+d Te 1−x S x samples, we performed component analysis and found that a weak acid such as an organic acid has the ability to induce superconductivity. Inductively coupled plasma spectroscopy was performed on weak acid solutions post-annealing. We found that the mechanism of inducement of superconductivity in Fe 1+d Te 1−x S x is the deintercalation of excess Fe from the interlayer sites. (paper)

  9. The cannabinoid receptor 2 agonist, β-caryophyllene, reduced voluntary alcohol intake and attenuated ethanol-induced place preference and sensitivity in mice.

    Al Mansouri, Shamma; Ojha, Shreesh; Al Maamari, Elyazia; Al Ameri, Mouza; Nurulain, Syed M; Bahi, Amine

    2014-09-01

    Several recent studies have suggested that brain CB2 cannabinoid receptors play a major role in alcohol reward. In fact, the implication of cannabinoid neurotransmission in the reinforcing effects of ethanol (EtOH) is becoming increasingly evident. The CB2 receptor agonist, β-caryophyllene (BCP) was used to investigate the role of the CB2 receptors in mediating alcohol intake and ethanol-induced conditioned place preference (EtOH-CPP) and sensitivity in mice. The effect of BCP on alcohol intake was evaluated using the standard two-bottle choice drinking method. The mice were presented with increasing EtOH concentrations and its consumption was measured daily. Consumption of saccharin and quinine solutions was measured following the EtOH preference tests. Finally, the effect of BCP on alcohol reward and sensitivity was tested using an unbiased EtOH-CPP and loss of righting-reflex (LORR) procedures, respectively. BCP dose-dependently decreased alcohol consumption and preference. Additionally, BCP-injected mice did not show any difference from vehicle mice in total fluid intake in a 24-hour paradigm nor in their intake of graded concentrations of saccharin or quinine, suggesting that the CB2 receptor activation did not alter taste function. More importantly, BCP inhibited EtOH-CPP acquisition and exacerbated LORR duration. Interestingly, these effects were abrogated when mice were pre-injected with a selective CB2 receptor antagonist, AM630. Overall, the CB2 receptor system appears to be involved in alcohol dependence and sensitivity and may represent a potential pharmacological target for the treatment of alcoholism. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Altered methylation and expression of ER-associated degradation factors in long-term alcohol and constitutive ER stress-induced murine hepatic tumors

    Hui eHan

    2013-10-01

    Full Text Available Mortality from liver cancer in humans is increasingly attributable to heavy or long-term alcohol consumption. The mechanisms by which alcohol exerts its carcinogenic effect are not well understood. In this study, the role of alcohol-induced endoplasmic reticulum (ER stress response in liver cancer development was investigated using an animal model with a liver knockout of the chaperone BiP and under constitutive hepatic ER stress. Long-term alcohol and high fat diet (HFD feeding resulted in higher levels of serum alanine aminotransferase (ALT, impaired ER stress response, and higher incidence of liver tumor in older (aged 16 months knockout females than in either middle-aged (6 months knockouts or older (aged 16 months wild type females. In the older knockout females, stronger effects of the alcohol on methylation of CpG islands at promoter regions of genes involved in the ER associated degradation (ERAD were also detected. Altered expression of ERAD factors including derlin 3, Creld2 (cysteine-rich with EGF-like domains 2, Herpud1 (ubiquitin-like domain member, Wfs1 (wolfram syndrome gene, and Yod1 (deubiquinating enzyme 1 was co-present with decreased proteasome activities, increased estrogen receptor alpha variant (ERa36, and enhanced phosphorylations of ERK1/2 (extracellular signal-regulated protein kinases 1 and 2 and STAT3 (the signal transducers and activators of transcription in the older knockout female fed alcohol. Our results suggest that long-term alcohol consumption and ageing may promote liver tumorigenesis in females through interfering with DNA methylation and expression of genes involved in the ER associated degradation.

  11. Steroid modulation of the chloride ionophore in rat brain: structure-activity requirements, regional dependence and mechanism of action

    Gee, K.W.; Bolger, M.B.; Brinton, R.E.; Coirini, H.; McEwen, B.S.

    1988-08-01

    Further in vitro studies of steroids active at the gamma-aminobutyric acidA (GABAA) receptor regulated Cl- channel labeled by (35S)-t-butylbicyclophosphorothionate ((35S)TBPS) reveal additional structural requirements necessary for activity. Evaluation of selected steroids for activity against TBPS-induced convulsions show similar requirements for activity. Interestingly, steroids (e.g., 5 alpha-pregnan-3 alpha, 20 alpha-diol) were identified that have high potency but limited efficacy as modulators of (35S)TBPS binding. These characteristics are reminiscent of the clinically useful benzodiazepines (BZs) such as clonazepam. However, interactions between the prototypical anesthetic-barbiturate, sodium pentobarbital, and steroids active at the Cl- channel suggest that they do not share a common site of action as allosteric modulators of (35S)TBPS and BZ receptor binding. The most potent steroid evaluated, 5 alpha-pregnan-3 alpha-ol-20-one, modulates (35S)TBPS binding at low concentrations (IC50 approximately 17 nM) in a regionally dependent manner. All (35S)TBPS binding sites appear to be functionally coupled to a steroid modulatory site. Because several of the active steroids are metabolites of progesterone, their ability to inhibit the binding of (3H)promegestrone to the cytosolic progestin receptor in rat uterus was evaluated. Those steroids showing potent activity at the GABAA receptor-Cl- ionophore were inactive at the intracellular progestin receptor. Such specificity coupled with their high potency provide additional support for the hypothesis that some of these steroids may be involved in the homeostatic regulation of brain excitability via the GABAA-BZ receptor complex.

  12. Chain reaction on de-halogenation of 1,2-dibromotetrafluoroethane and 1,1,2-trichlorotrifluoroethane induced by irradiation in alcohols

    Nakagawa, Seiko

    2015-01-01

    Methanol and 2-propanol solutions of 1,2-dibromotetrafluoroethane and 1,1,2-trichlorotrifluoroethane were irradiated with γ-rays after perfect de-oxygenation. The product, formed by the substitution of one of the bromine or chlorine atoms with a hydrogen atom, was observed by radiation-induced degradation and the product was also de-halogenated. The G-value of de-halogenation was more than a thousand times higher than G(e solv − ) and increased with the decreasing dose rate, meaning that a chain reaction is involved in the process. The efficiency of the degradation in 2-propanol was several times higher than that in methanol. It is concluded that the charge transfer from an alcohol radical will be the trigger of the chain reaction the same as in the degradation of hexachloroethane in alcohol solutions (Sawai et al., 1978). - Highlights: • Halone2402 and Furon113 were de-halogenated by radiation-induced chain reaction in pure alcohol. • The efficiency of the degradation in 2-propanol was several times higher than that in methanol. • The charge transfer from an alcohol radical will be the trigger of the chain reaction

  13. Neuroinflammation leads to region-dependent alterations in astrocyte gap junction communication and hemichannel activity.

    Karpuk, Nikolay; Burkovetskaya, Maria; Fritz, Teresa; Angle, Amanda; Kielian, Tammy

    2011-01-12

    Inflammation attenuates gap junction (GJ) communication in cultured astrocytes. Here we used a well-characterized model of experimental brain abscess as a tool to query effects of the CNS inflammatory milieu on astrocyte GJ communication and electrophysiological properties. Whole-cell patch-clamp recordings were performed on green fluorescent protein (GFP)-positive astrocytes in acute brain slices from glial fibrillary acidic protein-GFP mice at 3 or 7 d after Staphylococcus aureus infection in the striatum. Astrocyte GJ communication was significantly attenuated in regions immediately surrounding the abscess margins and progressively increased to levels typical of uninfected brain with increasing distance from the abscess proper. Conversely, astrocytes bordering the abscess demonstrated hemichannel activity as evident by enhanced ethidium bromide (EtBr) uptake that could be blocked by several pharmacological inhibitors, including the connexin 43 (Cx43) mimetic peptide Gap26, carbenoxolone, the pannexin1 (Panx1) mimetic peptide (10)Panx1, and probenecid. However, hemichannel opening was transient with astrocytic EtBr uptake observed near the abscess at day 3 but not day 7 after infection. The region-dependent pattern of hemichannel activity at day 3 directly correlated with increases in Cx43, Cx30, Panx1, and glutamate transporter expression (glial L-glutamate transporter and L-glutamate/L-aspartate transporter) along the abscess margins. Changes in astrocyte resting membrane potential and input conductance correlated with the observed changes in GJ communication and hemichannel activity. Collectively, these findings indicate that astrocyte coupling and electrical properties are most dramatically affected near the primary inflammatory site and reveal an opposing relationship between the open states of GJ channels versus hemichannels during acute infection. This relationship may extend to other CNS diseases typified with an inflammatory component.

  14. Characterizations and hepatoprotective effect of polysaccharides from Mori Fructus in rats with alcoholic-induced liver injury.

    Zhou, Xin; Deng, Qingfang; Chen, Huaguo; Hu, Enming; Zhao, Chao; Gong, Xiaojian

    2017-09-01

    Crude polysaccharides of Mori Fructus (MFPs) were found to have anti-inflammatory antioxidant, and immuno-enhancing activities. However, the structure of the polysaccharides was ambiguous and its holistic hepatic protection evaluation was defective. This study was conducted to illustrate the characterization of MFPs, and evaluate its hepatoprotective activities. The results found that MFPs contained 67.93±1.18% carbohydrates, 31.03±0.54% uronic acid, and little protein and sulfate. The average molecular weight was ranging from 112.2kDa to 181.9kDa. Monosaccharide component analysis indicated that MFPs was mainly composed of glucose, galacturonic acid, rhamnose and galactose. Both the acute and subacute alcoholic-induced liver injury animal models were adopted to evaluate the MFPs's hepatoprotective activity. After administration of MFPs, both serological indexes (aspartate aminotransferase and alanine aminotransferase) and hepatic indicators (glutathione, superoxide dismutase, glutathione peroxidase and malondialdehyde) were improved by comparing with the non-MFPs group. The hepatic histopathology results also showed a prominent lipid degeneration and microvesicular steatosis attenuation in the MFPs groups. These outstanding hepatic protecting activities of MFPs might be related to its activation of ethanol dehydrogenase, elimination of free radicals and/or inhibition of lipid peroxidation capacities. MFPs could be important active substances for preventing and remedying liver injury. Copyright © 2017. Published by Elsevier B.V.

  15. Gastroprotective effect and mechanism of patchouli alcohol against ethanol, indomethacin and stress-induced ulcer in rats.

    Zheng, Yi-Feng; Xie, Jian-Hui; Xu, Yi-Fei; Liang, Yong-Zhuo; Mo, Zhi-Zhun; Jiang, Wei-Wen; Chen, Xiao-Ying; Liu, Yu-Hong; Yu, Xiao-Dan; Huang, Ping; Su, Zi-Ren

    2014-10-05

    Pogostemonis Herba is an important Chinese medicine widely used in the treatment of gastrointestinal dysfunction. Patchouli alcohol (PA), a tricyclic sesquiterpene, is the major active constituent of Pogostemonis Herba. This study aimed to investigate the possible anti-ulcerogenic potential of PA and the underlying mechanism against ethanol, indomethacin and water immersion restraint-induced gastric ulcers in rats. Gross and histological gastric lesions, biochemical and immunological parameters were taken into consideration. The gastric mucus content and the antisecretory activity were analyzed through pylorus ligature model in rats. Results indicated that oral administration with PA significantly reduced the ulcer areas induced by ethanol, indomethacin and water immersion restraint. PA pretreatment significantly promoted gastric prostaglandin E2 (PGE2) and non-protein sulfhydryl group (NP-SH) levels, upregulated the cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) mRNA expression, and considerably boosted the gastric blood flow (GBF) and gastric mucus production in comparison with vehicle. In addition, PA modulated the levels of interleukin-6 (IL-6), interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α). The levels of glutathione (GSH), catalase (CAT) and malonaldehyde (MDA) were also restored by PA. However, the gastric secretion parameters (pH, volume of gastric juice and pepsin) did not show any significant alteration. These findings suggest that PA exhibited significant gastroprotective effects against gastric ulceration. The underlying mechanisms might involve the stimulation of COX-mediated PGE2, improvement of antioxidant and anti-inflammatory status, preservation of GBF and NP-SH, as well as boost of gastric mucus production. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  16. Adolescent Mice Are Resilient to Alcohol Withdrawal-Induced Anxiety and Changes in Indices of Glutamate Function within the Nucleus Accumbens.

    Lee, Kaziya M; Coelho, Michal A; McGregor, Hadley A; Solton, Noah R; Cohen, Matan; Szumlinski, Karen K

    2016-01-01

    Binge-drinking is the most prevalent form of alcohol abuse and while an early life history of binge-drinking is a significant risk factor for subsequent alcoholism and co-morbid affective disorders, relatively little is known regarding the biobehavioral impact of binge-drinking during the sensitive neurodevelopmental period of adolescence. In adult mice, a month-long history of binge-drinking elicits a hyper-glutamatergic state within the nucleus accumbens (Acb), coinciding with hyper-anxiety. Herein, we employed a murine model of binge-drinking to determine whether or not: (1) withdrawal-induced changes in brain and behavior differ between adult and adolescent bingers; and (2) increased behavioral signs of negative affect and changes in Acb expression of glutamate-related proteins would be apparent in adult mice with less chronic binge-drinking experience (14 days, approximating the duration of mouse adolescence). Adult and adolescent male C57BL/6J mice were subjected to a 14-day binge-drinking protocol (5, 10, 20 and 40% alcohol (v/v) for 2 h/day), while age-matched controls received water. At 24 h withdrawal, half of the animals from each group were assayed for negative affect, while tissue was sampled from the shell (AcbSh) and core (AcbC) subregions of the remaining mice for immunoblotting analyses. Adult bingers exhibited hyper-anxiety when tested for defensive marble burying. Additionally, adult bingers showed increased mGlu1, mGlu5, and GluN2b expression in the AcbSh and PKCε and CAMKII in the AcbC. Compared to adults, adolescent mice exhibited higher alcohol intake and blood alcohol concentrations (BACs); however, adolescent bingers did not show increased anxiety in the marble-burying test. Furthermore, adolescent bingers also failed to exhibit the same alcohol-induced changes in mGlu and kinase protein expression seen in the adult bingers. Irrespective of age, bingers exhibited behavioral hyperactivity in the forced swim test (FST) compared to water

  17. Adolescent mice are resilient to alcohol withdrawal-induced anxiety and changes in indices of glutamate function within the nucleus accumbens

    Kaziya M Lee

    2016-11-01

    Full Text Available Binge-drinking is the most prevalent form of alcohol abuse and while an early life history of binge-drinking is a significant risk factor for subsequent alcoholism and co-morbid affective disorders, relatively little is known regarding the biobehavioral impact of binge-drinking during the sensitive neurodevelopmental period of adolescence. In adult mice, a month-long history of binge-drinking elicits a hyper-glutamatergic state within the nucleus accumbens (Acb, coinciding with hyper-anxiety. Herein, we employed a murine model of binge-drinking to determine whether or not: 1 withdrawal-induced changes in brain and behavior differ between adult and adolescent bingers and 2 increased behavioral signs of negative affect and changes in Acb expression of glutamate-related proteins would be apparent in adult mice with less chronic binge-drinking experience (14 days, approximating the duration of mouse adolescence. Adult and adolescent male C57BL/6J mice were subjected to a 14-day binge-drinking protocol (5, 10, 20 and 40% alcohol (v/v for 2 h/day, while age-matched controls received water. At 24 h withdrawal, half of the animals from each group were assayed for negative affect, while tissue was sampled from the shell (AcbSh and core (AcbC subregions of the remaining mice for immunoblotting analyses. Adult bingers exhibited hyper-anxiety when tested for defensive marble burying. Additionally, adult bingers showed increased mGlu1, mGlu5, and GluN2b expression in the AcbSh and PKCε and CAMKII in the AcbC. Compared to adults, adolescent mice exhibited higher alcohol intake and blood alcohol concentrations; however, adolescent bingers did not show increased anxiety in the marble-burying test. Furthermore, adolescent bingers also failed to exhibit the same alcohol-induced changes in mGlu and kinase protein expression seen in the adult bingers. Irrespective of age, bingers exhibited behavioral hyperactivity in the forced swim test compared to water drinkers

  18. Non-invasive index of liver fibrosis induced by alcohol, thioacetamide and schistosomal infection in mice

    El-Beltagy Doha M

    2010-06-01

    Full Text Available Abstract Background Non invasive approaches will likely be increasing utilized to assess liver fibrosis. This work provides a new non invasive index to predict liver fibrosis induced in mice. Methods Fibrosis was generated by thioacetamide (TAA, chronic intake of ethanol, or infection with S. mansoni in 240 mice. Both progression and regression of fibrosis (after treatment with silymarin and/or praziquantel were monitored. The following methods were employed: (i The METAVIR system was utilized to grade and stage liver inflammation and fibosis; (ii Determination of hepatic hydroxyproline and collagen; and (iii Derivation of a new hepatic fibrosis index from the induced changes, and its prospective validation in a group of 70 mice. Results The index is composed of 4 serum variable including total proteins, γ-GT, bilirubin and reduced glutathione (GSH, measured in diseased, treated and normal mice. These parameters were highly correlated with both the histological stage and the grade. They were combined in a logarithmic formula, which non-invasively scores the severity of liver fibrosis through a range (0 to 2, starting with healthy liver (corresponding to stage 0 to advanced fibrosis (corresponding stage 3.Receiver operating characteristic curves (ROC for the accuracy of the index to predict the histological stages demonstrated that the areas under the curve (AUC were 0.954, 0.979 and 0.99 for index values corresponding to histological stages 1, 2 and 3, respectively. Also, the index was correlated with stage and grade, (0.947 and 0.859, respectively. The cut off values that cover the range between stages 0-1, 1-2 and 2-3 are 0.4, 1.12 and 1.79, respectively. The results in the validation group confirmed the accuracy of the test. The AUROC was 0.869 and there was good correlation with the stage of fibrosis and grade of inflammation. Conclusion The index fulfils the basic criteria of non-invasive marker of liver fibrosis since it is liver

  19. Disconnect between alcohol-induced alterations in chromatin structure and gene transcription in a mouse embryonic stem cell model of exposure.

    Veazey, Kylee J; Wang, Haiqing; Bedi, Yudhishtar S; Skiles, William M; Chang, Richard Cheng-An; Golding, Michael C

    2017-05-01

    Alterations to chromatin structure induced by environmental insults have become an attractive explanation for the persistence of exposure effects into subsequent life stages. However, a growing body of work examining the epigenetic impact that alcohol and other drugs of abuse exert consistently notes a disconnection between induced changes in chromatin structure and patterns of gene transcription. Thus, an important question is whether perturbations in the 'histone code' induced by prenatal exposures to alcohol implicitly subvert gene expression, or whether the hierarchy of cellular signaling networks driving development is such that they retain control over the transcriptional program. To address this question, we examined the impact of ethanol exposure in mouse embryonic stem cells cultured under 2i conditions, where the transcriptional program is rigidly enforced through the use of small molecule inhibitors. We find that ethanol-induced changes in post-translational histone modifications are dose-dependent, unique to the chromatin modification under investigation, and that the extent and direction of the change differ between the period of exposure and the recovery phase. Similar to in vivo models, we find post-translational modifications affecting histone 3 lysine 9 are the most profoundly impacted, with the signature of exposure persisting long after alcohol has been removed. These changes in chromatin structure associate with dose-dependent alterations in the levels of transcripts encoding Dnmt1, Uhrf1, Tet1, Tet2, Tet3, and Polycomb complex members Eed and Ezh2. However, in this model, ethanol-induced changes to the chromatin template do not consistently associate with changes in gene transcription, impede the process of differentiation, or affect the acquisition of monoallelic patterns of expression for the imprinted gene Igf2R. These findings question the inferred universal relevance of epigenetic changes induced by drugs of abuse and suggest that changes

  20. Genetic Deficiency in Neprilysin or Its Pharmacological Inhibition Initiate Excessive Stress-Induced Alcohol Consumption in Mice

    Gembardt, Florian; Becker, Axel; Schultheiss, Heinz-Peter; Siems, Wolf-Eberhard; Walther, Thomas

    2012-01-01

    Both acquired and inherited genetic factors contribute to excessive alcohol consumption and the corresponding development of addiction. Here we show that the genetic deficiency in neprilysin [NEP] did not change the kinetics of alcohol degradation but led to an increase in alcohol intake in mice in a 2-bottle-free-choice paradigm after one single stress stimulus (intruder). A repetition of such stress led to an irreversible elevated alcohol consumption. This phenomenon could be also observed in wild-type mice receiving an orally active NEP inhibitor. We therefore elucidated the stress behavior in NEP-deficient mice. In an Elevated Plus Maze, NEP knockouts crossed more often the area between the arms, implicating a significant stronger stress response. Furthermore, such animals showed a decreased locomotor activity under intense light in a locomotor activity test, identifying such mice to be more responsive in aversive situations than their wild-type controls. Since the reduction in NEP activity itself does not lead to significant signs of an altered alcohol preference in mice but requires an environmental stimulus, our findings build a bridge between stress components and genetic factors in the development of alcoholism. Therefore, targeting NEP activity might be a very attractive approach for the treatment of alcohol abuse in a society with increasing social and financial stress. PMID:23185571

  1. Genetic deficiency in neprilysin or its pharmacological inhibition initiate excessive stress-induced alcohol consumption in mice.

    Björn Maul

    Full Text Available Both acquired and inherited genetic factors contribute to excessive alcohol consumption and the corresponding development of addiction. Here we show that the genetic deficiency in neprilysin [NEP] did not change the kinetics of alcohol degradation but led to an increase in alcohol intake in mice in a 2-bottle-free-choice paradigm after one single stress stimulus (intruder. A repetition of such stress led to an irreversible elevated alcohol consumption. This phenomenon could be also observed in wild-type mice receiving an orally active NEP inhibitor. We therefore elucidated the stress behavior in NEP-deficient mice. In an Elevated Plus Maze, NEP knockouts crossed more often the area between the arms, implicating a significant stronger stress response. Furthermore, such animals showed a decreased locomotor activity under intense light in a locomotor activity test, identifying such mice to be more responsive in aversive situations than their wild-type controls. Since the reduction in NEP activity itself does not lead to significant signs of an altered alcohol preference in mice but requires an environmental stimulus, our findings build a bridge between stress components and genetic factors in the development of alcoholism. Therefore, targeting NEP activity might be a very attractive approach for the treatment of alcohol abuse in a society with increasing social and financial stress.

  2. Carvedilol Improves Inflammatory Response, Oxidative Stress and Fibrosis in the Alcohol-Induced Liver Injury in Rats by Regulating Kuppfer Cells and Hepatic Stellate Cells.

    Raimundo Fernandes de Araújo Júnior

    Full Text Available To evaluate the anti-inflammatory, anti-oxidant and antifibrotic effects of carvedilol (CARV in rats with ethanol-induced liver injury.Liver injury was induced by gavage administration of alcohol (7 g/kg for 28 consecutive days. Eighty Wistar rats were pretreated with oral CARV at 1, 3, or 5 mg/kg or with saline 1 h before exposure to alcohol. Liver homogenates were assayed for interleukin (IL-1β, IL-10, and tumor necrosis factor (TNF-α level as well as for myeloperoxidase (MPO activity and malonyldialdehyde (MDA and glutathione (GSH levels. Serum aspartate aminotransferase (AST activity and liver triglyceride (TG levels were also assayed. Immunohistochemical analyses of cyclooxygenase 2 (COX-2, receptor activator of nuclear factor kappa-B/ligand (RANK/RANKL, suppressor of cytokine signalling (SOCS1, the Kupffer cell marker IBA-1 (ionized calcium-binding adaptor molecule 1, intercellular adhesion molecule 1 (ICAM-1, superoxide dismutase (SOD-1, and glutathione peroxidase (GPx-1 expression were performed. Confocal microscopy analysis of IL-1β and NF-κB expression and real-time quantitative PCR analysis for TNFα, PCI, PCIII, and NF-κB were performed.CARV treatment (5 mg/kg during the alcohol exposure protocol was associated with reduced steatosis, hepatic cord degeneration, fibrosis and necrosis, as well as reduced levels of AST (p < 0.01, ALT (p < 0.01, TG (p < 0.001, MPO (p < 0.001, MDA (p < 0.05, and proinflammatory cytokines (IL-1β and TNF-α, both p < 0.05, and increased levels of the anti-inflammatory cytokine IL-10 (p < 0.001 and GSH (p < 0.05, compared to the alcohol-only group. Treatment with CARV 5 mg/kg also reduced expression levels of COX-2, RANK, RANKL, IBA-1, and ICAM-1 (all p < 0.05, while increasing expression of SOCS1, SOD-1, and GPx-1 (all p < 0.05 and decreasing expression of IL-1β and NF-κB (both, p < 0.05. Real-time quantitative PCR analysis showed that mRNA production of TNF-α, procollagen type I (PCI, procollagen

  3. Changes induced by UV radiation in the presence of sodium benzoate in films formulated with polyvinyl alcohol and carboxymethyl cellulose

    Villarruel, S. [Faculty of Exact Sciences, UNLP (Argentina); Giannuzzi, L.; Rivero, S. [Center for Research and Development in Food Cryotechnology (CCT-CONICET La Plata), 47 and 116 (Argentina); Pinotti, A., E-mail: acaimpronta@hotmail.com [Center for Research and Development in Food Cryotechnology (CCT-CONICET La Plata), 47 and 116 (Argentina); Faculty of Engineering, UNLP, La Plata 1900 (Argentina)

    2015-11-01

    This work was focused on: i) developing single and blend films based on carboxymethyl cellulose (CMC) and polyvinyl alcohol (PVOH) studying their properties, ii) analyzing the interactions between CMC and PVOH and their modifications UV-induced in the presence of sodium benzoate (SB), and iii) evaluating the antimicrobial capacity of blend films containing SB with and without UV treatment. Once the blend films with SB were exposed to UV radiation, they exhibited lower moisture content as well as a greater elongation at break and rougher surfaces compared to those without treatment. Considering oxygen barrier properties, the low values obtained would allow their application as packaging with selective oxygen permeability. Moreover, the characteristics of the amorphous phase of the matrix prevailed with a rearrangement of the structure of the polymer chain, causing a decrease of the crystallinity degree. These results were supported by X-rays and DSC analysis. FT-IR spectra reflected some degree of polymer–polymer interaction at a molecular level in the amorphous regions. The incorporation of sodium benzoate combined with UV treatment in blend films was positive from the microbial point of view because of the growth inhibition of a wide spectrum of microorganisms. From a physicochemical perspective, the UV treatment of films also changed their morphology rendering them more insoluble in water, turning the functionalized blend films into a potential material to be applied as food packaging. - Highlights: • CMC:PVOH blend films were developed with the addition of sodium benzoate (SB). • Exposition to UV radiation was carried out with sodium benzoate as photoinitiator. • Blend films were exposed to UV radiation to modify their surface morphology. • Low O{sub 2} permeability of UV treated blends allow them to be used as selective packaging. • Efficacy of SB as an antimicrobial agent was examined with and without UV radiation.

  4. Changes induced by UV radiation in the presence of sodium benzoate in films formulated with polyvinyl alcohol and carboxymethyl cellulose

    Villarruel, S.; Giannuzzi, L.; Rivero, S.; Pinotti, A.

    2015-01-01

    This work was focused on: i) developing single and blend films based on carboxymethyl cellulose (CMC) and polyvinyl alcohol (PVOH) studying their properties, ii) analyzing the interactions between CMC and PVOH and their modifications UV-induced in the presence of sodium benzoate (SB), and iii) evaluating the antimicrobial capacity of blend films containing SB with and without UV treatment. Once the blend films with SB were exposed to UV radiation, they exhibited lower moisture content as well as a greater elongation at break and rougher surfaces compared to those without treatment. Considering oxygen barrier properties, the low values obtained would allow their application as packaging with selective oxygen permeability. Moreover, the characteristics of the amorphous phase of the matrix prevailed with a rearrangement of the structure of the polymer chain, causing a decrease of the crystallinity degree. These results were supported by X-rays and DSC analysis. FT-IR spectra reflected some degree of polymer–polymer interaction at a molecular level in the amorphous regions. The incorporation of sodium benzoate combined with UV treatment in blend films was positive from the microbial point of view because of the growth inhibition of a wide spectrum of microorganisms. From a physicochemical perspective, the UV treatment of films also changed their morphology rendering them more insoluble in water, turning the functionalized blend films into a potential material to be applied as food packaging. - Highlights: • CMC:PVOH blend films were developed with the addition of sodium benzoate (SB). • Exposition to UV radiation was carried out with sodium benzoate as photoinitiator. • Blend films were exposed to UV radiation to modify their surface morphology. • Low O 2 permeability of UV treated blends allow them to be used as selective packaging. • Efficacy of SB as an antimicrobial agent was examined with and without UV radiation

  5. Effect of patchouli alcohol on the regulation of heat shock-induced oxidative stress in IEC-6 cells.

    Liu, Xiaoxi; Jiang, Linshu; Liu, Fenghua; Chen, Yuping; Xu, Lei; Li, Deyin; Ma, Yunfei; Li, Huanrong; Xu, Jianqin

    2016-08-01

    Purpose Patchouli alcohol (PA) is used to treat gastrointestinal dysfunction. The purpose of this study was to ascertain the function of PA in the regulated process of oxidative stress in rat intestinal epithelial cells (IEC-6). Materials and methods Oxidative stress was stimulated by exposing IEC-6 cells to heat shock (42 °C for 3 h). IEC-6 cells in treatment groups were pretreated with various concentrations of PA (10, 40, and 80 ng/mL) for 3 h before heat shock. Results Heat shock caused damage to the morphology of IEC-6 cells, and increased reactive oxygen species (ROS) level and malondialdehyde (MDA) content. Moreover, mRNA and protein expression by target genes related to oxidative stress in heat shock were also altered. Specifically, the mRNA expression by HSP70, HSP90, GSH-px, NRF2 nd HO-1were all increased, and Nrf2 and Keap1 protein expression were increased after heat shock. However, pretreatment with PA weakened the level of damage to the cellular morphology, and decreased the MDA content caused by heat shock, indicating PA had cytoprotective activities. Pretreatment with PA at high dose significantly increased generation of intracellular ROS. Compared with the heat shock group alone, PA pretreatment significantly decreased the mRNA expression by HSP70, HSP90, SOD, CAT, GSH-px, KEAP1 and HO-1. Furthermore, the high dose of PA significantly increased Nrf2 protein expression, while both the intermediate and high dose of PA significantly increased HO-1 protein expression. Conclusion Heat-shock-induced oxidative stress in IEC-6 cells, and PA could alleviate the Nrf2-Keap1 cellular oxidative stress responses.

  6. Protective influences of N-acetylcysteine against alcohol abstinence-induced depression by regulating biochemical and GRIN2A, GRIN2B gene expression of NMDA receptor signaling pathway in rats.

    Yawalkar, Rutuja; Changotra, Harish; Gupta, Girdhari Lal

    2018-04-25

    Evidences have indicated a high degree of comorbidity of alcoholism and depression. N-acetylcysteine (NAC) has shown its clinical efficiency in the treatment of several psychiatric disorders and is identified as a multi-target acting drug. The ability of NAC to prevent alcohol abstinence-induced depression-like effects and underlying mechanism(s) have not been adequately addressed. This study was aimed to investigate the beneficial effects of NAC in the alcohol abstinence-induced depression developed following long-term voluntary alcohol intake. For evaluation of the effects of NAC, Sprague-Dawley rats were enabled to voluntary drinking of 4.5%, 7.5% and 9% v/v alcohol for fifteen days. NAC (25, 50, and 100 mg/kg) and fluoxetine (5 mg/kg) were injected intraperitoneally for three consecutive days during the alcohol abstinence period on the days 16, 17, 18. The behavioral studies were conducted employing forced swim test (FST), and tail suspension test (TST) on day 18 to determine the effects of N-acetylcysteine and fluoxetine in the ethanol withdrawal induced-depression. Blood alcohol concentration, alcohol biomarkers like SGPT, SGOT, ALP, GGT, and MCV were estimated by using commercially available kits. Serotonin concentrations were measured in the plasma, hippocampus and pre-frontal cortex using the rat ELISA kit. The expression of GRIN1, GRIN2A, GRIN2B genes for the N-methyl d-aspartate receptors (NMDAR) subunits in the hippocampus and the prefrontal cortex were also examined by reverse-transcription quantitative polymerase chain reaction. The results revealed that alcohol abstinence group depicted increased immobility time in FST and TST. Further, NAC exerted significant protective effect at the doses 50 mg/kg and 100 mg/kg, but 25 mg/kg showed insignificant protection against alcohol abstinence-induced depression. The increased level of biochemical parameters following ethanol abstinence were also reversed by NAC at the dose of 100 mg/kg. The

  7. Cannabinoid receptor 2 agonist attenuates pain related behavior in rats with chronic alcohol/high fat diet induced pancreatitis.

    Zhang, Liping; Kline, Robert H; McNearney, Terry A; Johnson, Michael P; Westlund, Karin N

    2014-11-17

    Chronic Pancreatitis (CP) is a complex and multifactorial syndrome. Many contributing factors result in development of dysfunctional pain in a significant number of patients. Drugs developed to treat a variety of pain states fall short of providing effective analgesia for patients with chronic pancreatitis, often providing minimal to partial pain relief over time with significant side effects. Recently, availability of selective pharmacological tools has enabled great advances in our knowledge of the role of the cannabinoid receptors in pathophysiology. In particular, cannabinoid receptor 2 (CB2) has emerged as an attractive target for management of chronic pain, as demonstrated in several studies with inflammatory and neuropathic preclinical pain models. In this study, the analgesic efficacy of a novel, highly selective CB2 receptor agonist, LY3038404 HCl, is investigated in a chronic pancreatitis pain model, induced with an alcohol/high fat (AHF) diet. Rats fed the AHF diet developed visceral pain-like behaviors detectable by week 3 and reached a maximum at week 5 that persists as long as the diet is maintained. Rats with AHF induced chronic pancreatitis were treated with LY3038404 HCl (10 mg/kg, orally, twice a day for 9 days). The treated animals demonstrated significantly alleviated pain related behaviors after 3 days of dosing, including increased paw withdrawal thresholds (PWT), prolonged abdominal withdrawal latencies (ABWL), and decreased nocifensive responses to noxious 44°C hotplate stimuli. Terminal histological analysis of pancreatic tissue sections from the AHF chronic pancreatitis animals demonstrated extensive injury, including a global pancreatic gland degeneration (cellular atrophy), vacuolization (fat deposition), and fibrosis. After the LY3038404 HCl treatment, pancreatic tissue was significantly protected from severe damage and fibrosis. LY3038404 HCl affected neither open field exploratory behaviors nor dark/light box preferences as measures

  8. ALCOHOL I

    Despite the increase in alcohol marketing activities by the transnational alcohol corporations in Nigeria .... were recorded with a digital device with ..... era (i.e., before alcohol industry was es- tablished in ..... university student drinking: A na-.

  9. Ethanol-induced conditioned taste aversion in Warsaw Alcohol High-Preferring (WHP) and Warsaw Alcohol Low-Preferring (WLP) rats.

    Dyr, Wanda; Wyszogrodzka, Edyta; Paterak, Justyna; Siwińska-Ziółkowska, Agnieszka; Małkowska, Anna; Polak, Piotr

    2016-03-01

    The aversive action of the pharmacological properties of ethanol was studied in selectively bred Warsaw Alcohol High-Preferring (WHP) and Warsaw Alcohol Low-Preferring (WLP) rats. For this study, a conditioned-taste aversion test was used. Male WHP and WLP rats were submitted to daily 20-min sessions for 5 days, in which a saccharin solution (1.0 g/L) was available (pre-conditioning phase). Next, this drinking was paired with the injection of ethanol (0, 0.5, 1.0 g/kg), intraperitoneally [i.p.] immediately after removal of the saccharin bottle (conditioning phase). Afterward, the choice between the saccharin solution and water was extended for 18 subsequent days for 20-min daily sessions (post-conditioning phase). Both doses of ethanol did not produce an aversion to saccharin in WLP and WHP rats in the conditioning phase. However, injection of the 1.0 g/kg dose of ethanol produced an aversion in WLP rats that was detected by a decrease in saccharin intake at days 1, 3, 7, and 10 of the post-conditioning phase, with a decrease in saccharin preference for 16 days of the post-conditioning phase. Conditioned taste aversion, measured as a decrease in saccharin intake and saccharin preference, was only visible in WHP rats at day 1 and day 3 of the post-conditioning phase. This difference between WLP and WHP rats was apparent despite similar blood ethanol levels in both rat lines following injection of 0.5 and 1.0 g/kg of ethanol. These results may suggest differing levels of aversion to the post-ingestional effects of ethanol between WLP and WHP rats. These differing levels of aversion may contribute to the selected line difference in ethanol preference in WHP and WLP rats. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Protective Role of Dietary Curcumin in the Prevention of the Oxidative Stress Induced by Chronic Alcohol with respect to Hepatic Injury and Antiatherogenic Markers

    Ravi Varatharajalu

    2016-01-01

    Full Text Available Curcumin, an antioxidant compound found in Asian spices, was evaluated for its protective effects against ethanol-induced hepatosteatosis, liver injury, antiatherogenic markers, and antioxidant status in rats fed with Lieber-deCarli low menhaden (2.7% of total calories from ω-3 polyunsaturated fatty acids (PUFA and Lieber-deCarli high menhaden (13.8% of total calories from ω-3 PUFA alcohol-liquid (5% diets supplemented with or without curcumin (150 mg/kg/day for 8 weeks. Treatment with curcumin protected against high ω-3 PUFA and ethanol-induced hepatosteatosis and increase in liver injury markers, alanine aminotransferase, and aspartate aminotransferase. Curcumin upregulated paraoxonase 1 (PON1 mRNA and caused significant increase in serum PON1 and homocysteine thiolactonase activities as compared to high ω-3 PUFA and ethanol group. Moreover, treatment with curcumin protected against ethanol-induced oxidative stress by increasing the antioxidant glutathione and decreasing the lipid peroxidation adduct 4-hydroxynonenal. These results strongly suggest that chronic ethanol in combination with high ω-3 PUFA exacerbated hepatosteatosis and liver injury and adversely decreases antiatherogenic markers due to increased oxidative stress and depletion of glutathione. Curcumin supplementation significantly prevented these deleterious actions of chronic ethanol and high ω-3 PUFA. Therefore, we conclude that curcumin may have therapeutic potential to protect against chronic alcohol-induced liver injury and atherosclerosis.

  11. Effects of BCL oral administation and herbal acupuncture at BL18, BL19 on Liver function changes induced by Alcohol in the mice

    Sa-Hyun Park

    2002-02-01

    Full Text Available This dissertation was designed to evaluate the effect of BCL(refinded Bambusae Caulis in Liqua-men oral administration and herbal acupuncture on alcohol metabolism and liver function. For this study. mice were damaged by a large quantity of alcohol and received treatment of either BCL 1 mg/kg in oral or BCL 250㎍/kg in herbal acupuncture-BL18 . BL19 bilateral. and then such parameters as GOT. GPT. catalase and superoxide dismustase(CuZn-SOD, Mn-SOD were measured. The results of the experiments were summarized as follows. 1. Compared with control group, the proper degree of alcohol in serum was not significantly differ from oral administration group and herbal acupuncture group. 2. Compared with control group. the activity of GOT in serum was significantly reduced both oral administration and herbal acupuncture group. 3. Compared with control group. the activity of GPT in serum was significantly reduced both oral administration and herbal acupuncture group. 4. The activity of catalase in liver cell tissue, compared with control group. was not sigificantly affected either by oral administration and herbal acupuncture group. 5. The activity of CuZn-SOD in liver cell tissue was not significantly change in herbal acupuncture and oral administration group. The activity of Mn-SOD was significantly increased in oral administration group. while it was not the case in acupuncture group. In conclusion. we consider that BCL oral administration and herbal acupuncture is highly effetive in recovering alcohol metabolism and liver disfunction induced by alcohol.

  12. Moderate acute intake of de-alcoholised red wine, but not alcohol, is protective against radiation-induced DNA damage ex vivo-Results of a comparative in vivo intervention study in younger men

    Greenrod, W. [CSIRO Health Sciences and Nutrition, Genome Health and Nutrigenomics Laboratory, PO Box 10041, Adelaide BC, SA 5000 (Australia); Department of Clinical and Experimental Pharmacology, University of Adelaide, South Australia (Australia); Stockley, C.S. [Australian Wine Research Institute, South Australia (Australia); Burcham, P. [Department of Clinical and Experimental Pharmacology, University of Adelaide, South Australia (Australia); Abbey, M. [CSIRO Health Sciences and Nutrition, Genome Health and Nutrigenomics Laboratory, PO Box 10041, Adelaide BC, SA 5000 (Australia); Fenech, M. [CSIRO Health Sciences and Nutrition, Genome Health and Nutrigenomics Laboratory, PO Box 10041, Adelaide BC, SA 5000 (Australia)]. E-mail: michael.fenech@hsn.csiro.au

    2005-12-11

    Moderate intake of wine is associated with reduced risk of cardiovascular disease and possibly cancer however it remains unclear whether the potential health benefits of wine intake are due to alcohol or the non-alcoholic fraction of wine. We therefore tested the hypothesis that the non-alcoholic fraction of wine protects against genome damage induced by oxidative stress in a crossover intervention study involving six young adult males aged 21-26 years. The participants adhered to a low plant phenolic compound diet for 48 h prior to consuming 300 mL of complete red wine, dealcoholised red wine or ethanol on separate occasions 1 week apart. Blood samples were collected 0.5, 1.0 and 2.0 h after beverage consumption. Baseline and radiation-induced genome damage was measured using the cytokinesis-block micronucleus assay and total plasma catechin concentration was measured. Consumption of dealcoholised red wine significantly decreased the gamma radiation-induced DNA damage at 1 and 2 h post-consumption by 20%. In contrast alcohol tended to increase radiation-induced genome damage and complete wine protected against radiation-induced genome damage relative to alcohol. The observed effects were only weakly correlated with the concentration of total plasma catechin (R = -0.23). These preliminary data suggest that only the non-alcoholic fraction of red wine protects DNA from oxidative damage but this effect cannot be explained solely by plasma catechin.

  13. Moderate acute intake of de-alcoholised red wine, but not alcohol, is protective against radiation-induced DNA damage ex vivo-Results of a comparative in vivo intervention study in younger men

    Greenrod, W.; Stockley, C.S.; Burcham, P.; Abbey, M.; Fenech, M.

    2005-01-01

    Moderate intake of wine is associated with reduced risk of cardiovascular disease and possibly cancer however it remains unclear whether the potential health benefits of wine intake are due to alcohol or the non-alcoholic fraction of wine. We therefore tested the hypothesis that the non-alcoholic fraction of wine protects against genome damage induced by oxidative stress in a crossover intervention study involving six young adult males aged 21-26 years. The participants adhered to a low plant phenolic compound diet for 48 h prior to consuming 300 mL of complete red wine, dealcoholised red wine or ethanol on separate occasions 1 week apart. Blood samples were collected 0.5, 1.0 and 2.0 h after beverage consumption. Baseline and radiation-induced genome damage was measured using the cytokinesis-block micronucleus assay and total plasma catechin concentration was measured. Consumption of dealcoholised red wine significantly decreased the gamma radiation-induced DNA damage at 1 and 2 h post-consumption by 20%. In contrast alcohol tended to increase radiation-induced genome damage and complete wine protected against radiation-induced genome damage relative to alcohol. The observed effects were only weakly correlated with the concentration of total plasma catechin (R = -0.23). These preliminary data suggest that only the non-alcoholic fraction of red wine protects DNA from oxidative damage but this effect cannot be explained solely by plasma catechin

  14. Prognostic value of insulinlike growth factor I and its binding protein in patients with alcohol-induced liver disease. EMALD group

    Møller, Søren; Becker, Povl Ulrik; Juul, A

    1996-01-01

    Insulinlike growth factor I (IGF-I) is a single-polypeptide chain with important anabolic and endocrine activities. The liver is the major source of IGF-I and its binding protein, IGFBP-3. Circulating concentrations of IGF-I and IGFBP-3 are decreased in patients with chronic liver disease...... and correlate with the severity. The aim of this study was to assess the additional prognostic value of IGF-I and IGFBP-3 in patients entered in a large multicenter study (EMALD). Three hundred thirty-seven patients with alcohol-induced liver disease were studied in a randomized placebo-controlled trial...... of malotilate with a mean follow-up period of 569 days (range, 7-1,544). A multivariate Cox regression analysis of pertinent clinical and biochemical variables showed a significant independent prognostic value of years of alcohol intake, coagulation factors 2, 7, and 10, alkaline phosphatases, serum creatinine...

  15. Evaluation of retinal nerve fiber layer thickness measurements using optical coherence tomography in patients with tobacco-alcohol-induced toxic optic neuropathy

    Moura Frederico

    2010-01-01

    Full Text Available Three patients with progressive visual loss, chronic alcoholism and tabagism were submitted to a complete neuro-ophthalmic examination and to retinal nerve fiber layer (RNFL measurements using optical coherence tomography (OCT scanning. Two patients showed marked RNFL loss in the temporal sector of the optic disc. However, a third patient presented RNFL measurements within or above normal limits, based on the Stratus-OCT normative database. Such findings may be due to possible RNFL edema similar to the one that may occur in the acute phase of toxic optic neuropathies. Stratus-OCT was able to detect RNFL loss in the papillomacular bundle of patients with tobacco-alcohol-induced toxic optic neuropathy. However, interpretation must be careful when OCT does not show abnormality in order to prevent diagnostic confusion, since overestimation of RNFL thickness measurements is possible in such cases.

  16. Influence of the novel histamine H₃ receptor antagonist ST1283 on voluntary alcohol consumption and ethanol-induced place preference in mice.

    Bahi, Amine; Sadek, Bassem; Schwed, Stephan J; Walter, Miriam; Stark, Holger

    2013-07-01

    Growing evidence supports a role for the central histaminergic system to have a modulatory influence on drug addiction in general and alcohol-use disorders in particular through histamine H3 receptors (H3R). In the present study, the effects of systemic injection of the newly synthesized H3R antagonist ST1283 on ethanol (EtOH) voluntary intake and EtOH-conditioned reward in mice have been investigated. Oral EtOH, saccharin, and quinine intake was assessed in a two-bottle choice paradigm using escalating concentrations of alcohol or tastant solutions. EtOH-induced place preference (CPP), EtOH-induced locomotor activity, and blood ethanol concentration (BEC) were also measured. Following administration of the H3R antagonist (2.5, 5, and 10 mg/kg, i.p.), there was a significant dose-dependent decrease in alcohol consumption and preference. Importantly, vehicle- and ST1283 (5 mg/kg)-treated mice showed similar consumption and preference to increasing concentration of both sweet and bitter tastes. More interestingly, systemic administration of ST1283 inhibited EtOH-CPP and EtOH-enhanced locomotion. This inhibition was blocked when mice were pretreated with the selective H3R agonist R-(alpha)-methyl-histamine (10 mg/kg). Finally, vehicle- and ST1283-treated mice had similar BECs. Our results show that ST1283 may decrease voluntary EtOH consumption and EtOH-CPP by altering its reinforcing effects, suggesting a novel role for histamine signaling in regulation of alcoholism. Lastly, the results add to the growing literature on H3R modulation in the pharmacotherapy of EtOH addiction.

  17. Effects of Alcohol on Plasma Glucose and Prevention of Alcohol-induced Hypoglycemia in Type 1 Diabetes - A Systematic Review with GRADE

    Tetzschner, R; Nørgaard, K; Ranjan, A

    2018-01-01

    systematically reviewed the literature for ethanol effects on plasma glucose and for prevention strategies on ethanol-induced hypoglycemia. METHODS: Electronic searches on PubMed and Google were conducted in February 2017. Randomized clinical trials and observational studies were included. Studies involved...... patients with T1D with no history of ethanol abuse. The primary aims were changes in plasma glucose after ethanol intake and prevention strategies for ethanol-induced hypoglycemia. Quality of the studies was assessed by GRADE. Additionally, we searched for guidelines from diabetes associations...

  18. Polyhydroxylated fatty alcohols derived from avocado suppress inflammatory response and provide non-sunscreen protection against UV-induced damage in skin cells.

    Rosenblat, Gennady; Meretski, Shai; Segal, Joseph; Tarshis, Mark; Schroeder, Avi; Zanin-Zhorov, Alexandra; Lion, Gilead; Ingber, Arieh; Hochberg, Malka

    2011-05-01

    Exposing skin to ultraviolet (UV) radiation contributes to photoaging and to the development of skin cancer by DNA lesions and triggering inflammatory and other harmful cellular cascades. The present study tested the ability of unique lipid molecules, polyhydroxylated fatty alcohols (PFA), extracted from avocado, to reduce UVB-induced damage and inflammation in skin. Introducing PFA to keratinocytes prior to their exposure to UVB exerted a protective effect, increasing cell viability, decreasing the secretion of IL-6 and PGE(2), and enhancing DNA repair. In human skin explants, treating with PFA reduced significantly UV-induced cellular damage. These results support the idea that PFA can play an important role as a photo-protective agent in UV-induced skin damage.

  19. Black Alcoholism.

    Watts, Thomas D.; Wright, Roosevelt

    1988-01-01

    Examines some aspects of the problem of alcoholism among Blacks, asserting that Black alcoholism can best be considered in an ecological, environmental, sociocultural, and public health context. Notes need for further research on alcoholism among Blacks and for action to reduce the problem of Black alcoholism. (NB)

  20. High fat diet-induced non alcoholic fatty liver disease in rats is associated with hyperhomocysteinemia caused by down regulation of the transsulphuration pathway

    Napolitano Mariarosaria

    2011-04-01

    Full Text Available Abstract Background Hyperhomocysteinemia (HHcy causes increased oxidative stress and is an independent risk factor for cardiovascular disease. Oxidative stress is now believed to be a major contributory factor in the development of non alcoholic fatty liver disease, the most common liver disorder worldwide. In this study, the changes which occur in homocysteine (Hcy metabolism in high fat-diet induced non alcoholic fatty liver disease (NAFLD in rats were investigated. Methods and results After feeding rats a standard low fat diet (control or a high fat diet (57% metabolisable energy as fat for 18 weeks, the concentration of homocysteine in the plasma was significantly raised while that of cysteine was lowered in the high fat as compared to the control diet fed animals. The hepatic activities of cystathionine β-synthase (CBS and cystathionine γ-lyase (CGS, the enzymes responsible for the breakdown of homocysteine to cysteine via the transsulphuration pathway in the liver, were also significantly reduced in the high fat-fed group. Conclusions These results indicate that high fat diet-induced NAFLD in rats is associated with increased plasma Hcy levels caused by down-regulation of hepatic CBS and CGL activity. Thus, HHcy occurs at an early stage in high fat diet-induced NAFLD and is likely to contribute to the increased risk of cardiovascular disease associated with the condition.

  1. Fatty acid composition and mechanisms of the protective effects of myrtle berry seed aqueous extract in alcohol-induced peptic ulcer in rat.

    Jabri, Mohamed-Amine; Rtibi, Kais; Tounsi, Haifa; Hosni, Karim; Marzouki, Lamjed; Sakly, Mohsen; Sebai, Hichem

    2017-05-01

    This study aimed to investigate the antiulcer and antioxidant activities of myrtle berry seed aqueous extract (MBSAE) in a peptic ulcer model induced by ethanol in male Wistar rats. MBSAE is rich in total polyphenols, total flavonoids, and unsaturated fatty acids, particularly linoleic (18:2) and oleic (18:1) acids. MBSAE also exhibited in vitro antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH) (IC 50 = 172.1 μg/mL) and superoxide anion (IC 50 = 200.24 μg/mL) scavenging activities. In vivo, MBSAE provided dose-dependent protection against ethanol-induced gastric and duodenal macroscopic and histological alterations. Also, it inhibited secretory profile disturbances and lipid peroxidation, and preserved normal antioxidant enzyme activities and nonenzymatic antioxidant levels. More importantly, we showed that acute alcohol intoxication increased gastric and duodenal calcium, hydrogen peroxide, and free iron levels, whereas MBSAE treatment protected against intracellular mediator deregulation. In conclusion, we suggest that MBSAE has potent protective effects against alcohol-induced peptic ulcer in rat. This protection might be related in part to its antioxidant properties as well as its opposite effects on some studied intracellular mediators.

  2. Selective Hydrogen Atom Abstraction through Induced Bond Polarization: Direct α-Arylation of Alcohols through Photoredox, HAT, and Nickel Catalysis.

    Twilton, Jack; Christensen, Melodie; DiRocco, Daniel A; Ruck, Rebecca T; Davies, Ian W; MacMillan, David W C

    2018-05-04

    The combination of nickel metallaphotoredox catalysis, hydrogen atom transfer catalysis, and a Lewis acid activation mode, has led to the development of an arylation method for the selective functionalization of alcohol α-hydroxy C-H bonds. This approach employs zinc-mediated alcohol deprotonation to activate α-hydroxy C-H bonds while simultaneously suppressing C-O bond formation by inhibiting the formation of nickel alkoxide species. The use of Zn-based Lewis acids also deactivates other hydridic bonds such as α-amino and α-oxy C-H bonds. This approach facilitates rapid access to benzylic alcohols, an important motif in drug discovery. A 3-step synthesis of the drug Prozac exemplifies the utility of this new method. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Effects of hydro-alcoholic extract of Vitex agnus-castus fruit on kidney of D-galactose-induced aging model in female mice

    Oroojan, A. A.; Ahangarpour, A.; Khorsandi, L.; Najimi, S. A.

    2016-01-01

    The aim of the present study was to evaluate the effect of a hydro-alcoholic extract of Vitex agnus-castus (VAC) fruit on blood urea nitrogen (BUN), creatinine (Cr) and, kidney histology of a female mouse model of D-galactose induced aging. In this experimental study, 72 NMRI mice were divided into 6 groups: control, VAC, D-galactose, D-galactose+VAC, aging, and aging+VAC. D-galactose was injected for 45 days and, VAC extract administered in the last 7 days, twice a day. Serum BUN and Cr leve...

  4. The neurosteroid pregnenolone sulfate neutralized the learning impairment induced by intrahippocampal nicotine in alcohol-drinking rats.

    Martín-García, E; Pallarès, M

    2005-01-01

    The effects of intrahippocampal administration of nicotine and the neurosteroids pregnenolone sulfate and allopregnanolone on acquiring the lever-press response and extinction in a Skinner box were examined using voluntary alcohol-drinking rats. A free-choice drinking procedure that implies early availability of the alcoholic solution (10% ethanol v/v+3% glucose w/v in distilled water) was used. Alcohol and control rats were deprived of food and assigned at random to six groups. Each group received two consecutive intrahippocampal (dorsal CA1) injections immediately after 1-h of drinking ethanol and before the free lever-press response shaping and extinction session. The groups were: saline-saline; saline-pregnenolone sulfate (5 ng, 24 microM); saline-allopregnanolone (0.2 microg, 1.26 microM); nicotine (4.6 microg, 20 mM)-saline; nicotine-pregnenolone sulfate; nicotine-allopregnanolone. Blood alcohol concentrations were assessed the day before conditioning. The combination of the oral self-administration of ethanol and the intrahippocampal injection of nicotine deteriorated the ability to acquire the lever-press response. This effect was neutralized by intrahippocampal pregnenolone sulfate (negative modulator of the GABA(A) receptor complex), and it was not affected by intrahippocampal allopregnanolone (positive GABA receptor complex A modulator). Pregnenolone sulfate and allopregnanolone had no effects per se on lever-press acquisition, neither in alcohol-drinking rats nor in controls. Alcohol consumption facilitated operant extinction just as anxiolytics that act as positive modulators of the GABA receptor complex A receptors do, possibly reducing the anxiety or aversion related to non-reinforcement. This effect was increased by intrahippocampal nicotine.

  5. Alcoholic hallucinosis: case report

    Bárbara Werner Griciunas

    2017-03-01

    Full Text Available Case report of patient who has been an alcoholic for 40 years and, after reducing alcohol intake, developed auditory and visual hallucinations, which caused behavior change. Neurological issues, electrolyte disturbances and other organ dysfunctions were excluded as cause of said change. After intake of haloperidol and risperidone, the patient had regression of symptoms and denied having presented hallucinatory symptoms. The Manual Diagnóstico e Estatístico de Transtornos Mentais – 5ª edição (DSM-V includes alcoholic hallucinosis in the Substance-Induced Psychotic Disorder (alcohol, beginning during abstinence; however, the document is not yet very well accepted among the medical community. The difficulty of the team to confirm the diagnosis of alcoholic hallucinosis lies in the differential diagnosis, as Delirium tremens and severe withdrawal syndrome with psychotic symptoms. Thus, psychopathological differentiation is important, as well as continuity of research and collaboration of other clinical teams in the evaluation.

  6. The radiation-induced inactivation of microorganisms in non-aqueous suspension: The effect of selective alcohols and paraffins on the radiation sensitivity of aerated Bacillus pumilus spores

    Jacobs, G.P.

    1981-01-01

    The effect of model compounds comprising alcohols and paraffins on the radiation sensitivity of B. pumilus spores has been studied with the aim of understanding the radiation-induced inactivation of microorganisms when suspended in non-aqueous medium. This study is a prerequisite to the undertaking of radiation sterilization of non-aqueous pharmaceuticals. Spores of B. pumilus E601 mounted on kaolin powder were suspended in the appropriate organic agent and gamma irradiated under oxic conditions. Spores suspended in paraffins displayed increased radiation response over that for aerated buffered suspensions. Values of inactivation constant ranged between 2 x and 5 x that for buffer. Less pronounced modification of response was obtained for the alcohols. The results reveal a marked tendency for response to increase with decreasing polarity of the supending fluid. The partial miscibility of the alcohols in water enabled the examining of the transition from the response characteristic of aerated buffered suspensions to those of the spores in pure organic liquids. (orig./MG) [de

  7. Therapeutic role of ursolic acid on ameliorating hepatic steatosis and improving metabolic disorders in high-fat diet-induced non-alcoholic fatty liver disease rats.

    Li, Songtao; Liao, Xilu; Meng, Fanyu; Wang, Yemei; Sun, Zongxiang; Guo, Fuchuan; Li, Xiaoxia; Meng, Man; Li, Ying; Sun, Changhao

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent liver diseases around the world, and is closely associated with obesity, diabetes, and insulin resistance. Ursolic acid (UA), an ubiquitous triterpenoid with multifold biological roles, is distributed in various plants. This study was conducted to investigate the therapeutic effect and potential mechanisms of UA against hepatic steatosis in a high-fat diet (HFD)-induced obese non-alcoholic fatty liver disease (NAFLD) rat model. Obese NAFLD model was established in Sprague-Dawley rats by 8-week HFD feeding. Therapeutic role of UA was evaluated using 0.125%, 0.25%, 0.5% UA-supplemented diet for another 6 weeks. The results from both morphologic and histological detections indicated that UA significantly reversed HFD-induced hepatic steatosis and liver injury. Besides, hepatic peroxisome proliferator-activated receptor (PPAR)-α was markedly up-regulated at both mRNA and protein levels by UA. Knocking down PPAR-α significantly inhibited the anti-steatosis role of UA in vitro. HFD-induced adverse changes in the key genes, which participated in hepatic lipid metabolism, were also alleviated by UA treatment. Furthermore, UA significantly ameliorated HFD-induced metabolic disorders, including insulin resistance, inflammation and oxidative stress. These results demonstrated that UA effectively ameliorated HFD-induced hepatic steatosis through a PPAR-α involved pathway, via improving key enzymes in the controlling of lipids metabolism. The metabolic disorders were accordingly improved with the decrease of hepatic steatosis. Thereby, UA could be a promising candidate for the treatment of NAFLD.

  8. Therapeutic role of ursolic acid on ameliorating hepatic steatosis and improving metabolic disorders in high-fat diet-induced non-alcoholic fatty liver disease rats.

    Songtao Li

    Full Text Available BACKGROUND: Non-alcoholic fatty liver disease (NAFLD is one of the most prevalent liver diseases around the world, and is closely associated with obesity, diabetes, and insulin resistance. Ursolic acid (UA, an ubiquitous triterpenoid with multifold biological roles, is distributed in various plants. This study was conducted to investigate the therapeutic effect and potential mechanisms of UA against hepatic steatosis in a high-fat diet (HFD-induced obese non-alcoholic fatty liver disease (NAFLD rat model. METHODOLOGY/PRINCIPAL FINDINGS: Obese NAFLD model was established in Sprague-Dawley rats by 8-week HFD feeding. Therapeutic role of UA was evaluated using 0.125%, 0.25%, 0.5% UA-supplemented diet for another 6 weeks. The results from both morphologic and histological detections indicated that UA significantly reversed HFD-induced hepatic steatosis and liver injury. Besides, hepatic peroxisome proliferator-activated receptor (PPAR-α was markedly up-regulated at both mRNA and protein levels by UA. Knocking down PPAR-α significantly inhibited the anti-steatosis role of UA in vitro. HFD-induced adverse changes in the key genes, which participated in hepatic lipid metabolism, were also alleviated by UA treatment. Furthermore, UA significantly ameliorated HFD-induced metabolic disorders, including insulin resistance, inflammation and oxidative stress. CONCLUSIONS/SIGNIFICANCE: These results demonstrated that UA effectively ameliorated HFD-induced hepatic steatosis through a PPAR-α involved pathway, via improving key enzymes in the controlling of lipids metabolism. The metabolic disorders were accordingly improved with the decrease of hepatic steatosis. Thereby, UA could be a promising candidate for the treatment of NAFLD.

  9. The novel non-imidazole histamine H3 receptor antagonist DL77 reduces voluntary alcohol intake and ethanol-induced conditioned place preference in mice.

    Bahi, Amine; Sadek, Bassem; Nurulain, Syed M; Łażewska, Dorota; Kieć-Kononowicz, Katarzyna

    2015-11-01

    It has become clear that histamine H3 receptors (H3R) have been implicated in modulating ethanol intake and preference in laboratory animals. The novel non-imidazole H3R antagonist DL77 with excellent selectivity profile shows high in-vivo potency as well as in-vitro antagonist affinity with ED50 of 2.1 ± 0.2 mg/kg and pKi=8.08, respectively. In the present study, and applying an unlimited access two-bottle choice procedure, the anti-alcohol effects of the H3R antagonist, DL77 (0, 3, 10 and 30 mg/kg; i.p.), were investigated in adult mice. In this C57BL/6 line, effects of DL77 on voluntary alcohol intake and preference, as well as on total fluid intake were evaluated. Results have shown that DL77, dose-dependently, reduced both ethanol intake and preference. These effects were very selective as both saccharin and quinine, used to control for taste sensitivity, and intakes were not affected following DL77 pre-application. More importantly, systemic administration of DL77 (10 mg/kg) during acquisition inhibited ethanol-induced conditioned-place preference (EtOH-CPP) as measured using an unbiased protocol. The anti-alcohol activity observed for DL77 was abrogated when mice were pretreated with the selective H3R agonist R-(α)-methyl-histamine (RAMH) (10 mg/kg), or with the CNS penetrant H1R antagonist pyrilamine (PYR) (10mg/kg). These results suggest that DL77 has a predominant role in two in vivo effects of ethanol. Therefore, signaling via H3R is essential for ethanol-related consumption and conditioned reward and may represent a novel therapeutic pharmacological target to tackle ethanol abuse and alcoholism. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Early diet-induced non-alcoholic steatohepatitis in APOE2 knock-in mice and its prevention by fibrates

    Shiri-Sverdlov, Ronit; Wouters, Kristiaan; van Gorp, Patrick J.; Gijbels, Marion J.; Noel, Benoit; Buffat, Laurent; Staels, Bart; Maeda, Nobuyo; van Bilsen, Marc; Hofker, Marten H.

    2006-01-01

    The molecular mechanisms leading to Non-Alcoholic Steatohepatitis (NASH) are not fully understood. In mice, NASH can be inhibited by fenofibrate, a synthetic agonist for the nuclear receptor peroxisome proliferator activated receptor alpha, which regulates hepatic triglyceride metabolism. This study

  11. Pathophysiology of alcoholic pancreatitis: An overview

    Parimal Chowdhury; Priya Gupta

    2006-01-01

    Use of alcohol is a worldwide habit regardless of socioeconomic background. Heavy alcohol consumption is a potential risk factor for induction of pancreatitis. The current review cites the updated literature on the alcohol metabolism, its effects on gastrointestinal and pancreatic function and in causing pancreatic injury, genetic predisposition of alcohol induced pancreatitis. Reports describing prospective mechanisms of action of alcohol activating the signal transduction pathways, induction of oxidative stress parameters through the development of animal models are being presented.

  12. Molecular basis of alcoholism.

    Most, Dana; Ferguson, Laura; Harris, R Adron

    2014-01-01

    Acute alcohol intoxication causes cellular changes in the brain that last for hours, while chronic alcohol use induces widespread neuroadaptations in the nervous system that can last a lifetime. Chronic alcohol use and the progression into dependence involve the remodeling of synapses caused by changes in gene expression produced by alcohol. The progression of alcohol use, abuse, and dependence can be divided into stages, which include intoxication, withdrawal, and craving. Each stage is associated with specific changes in gene expression, cellular function, brain circuits, and ultimately behavior. What are the molecular mechanisms underlying the transition from recreational use (acute) to dependence (chronic)? What cellular adaptations result in drug memory retention, leading to the persistence of addictive behaviors, even after prolonged drug abstinence? Research into the neurobiology of alcoholism aims to answer these questions. This chapter will describe the molecular adaptations caused by alcohol use and dependence, and will outline key neurochemical participants in alcoholism at the molecular level, which are also potential targets for therapy. © 2014 Elsevier B.V. All rights reserved.

  13. Alcohol and atherosclerosis

    DA LUZ PROTASIO L.

    2001-01-01

    Full Text Available Atherosclerosis is manifested as coronary artery disease (CAD, ischemic stroke and peripheral vascular disease. Moderate alcohol consumption has been associated with reduction of CAD complications. Apparently, red wine offers more benefits than any other kind of drinks, probably due to flavonoids. Alcohol alters lipoproteins and the coagulation system. The flavonoids induce vascular relaxation by mechanisms that are both dependent and independent of nitric oxide, inhibits many of the cellular reactions associated with atherosclerosis and inflammation, such as endothelial expression of vascular adhesion molecules and release of cytokines from polymorphonuclear leukocytes. Hypertension is also influenced by the alcohol intake. Thus, heavy alcohol intake is almost always associated with systemic hypertension, and hence shall be avoided. In individuals that ingest excess alcohol, there is higher risk of coronary occlusion, arrhythmias, hepatic cirrhosis, upper gastrointestinal cancers, fetal alcohol syndrome, murders, sex crimes, traffic and industrial accidents, robberies, and psychosis. Alcohol is no treatment for atherosclerosis; but it doesn't need to be prohibited for everyone. Thus moderate amounts of alcohol (1-2 drinks/day, especially red wine, may be allowed for those at risk for atherosclerosis complications.

  14. Hepatoprotective Effects of Antrodia cinnamomea: The Modulation of Oxidative Stress Signaling in a Mouse Model of Alcohol-Induced Acute Liver Injury

    Yange Liu

    2017-01-01

    Full Text Available In the present study, the components of A. cinnamomea (AC mycelia were systematically analyzed. Subsequently, its hepatoprotective effects and the underlying mechanisms were explored using a mouse model of acute alcohol-induced liver injury. AC contained 25 types of fatty acid, 16 types of amino acid, 3 types of nucleotide, and 8 types of mineral. The hepatoprotective effects were observed after 2 weeks of AC treatment at doses of 75 mg/kg, 225 mg/kg, and 675 mg/kg in the mouse model. These effects were indicated by the changes in the levels of aspartate aminotransferase, alanine aminotransferase, several oxidation-related factors, and inflammatory cytokines in serum and/or liver samples. AC reduced the incidence rate of necrosis, inflammatory infiltration, fatty droplets formation, and cell apoptosis in liver detecting via histological and TUNEL assay. In addition, AC reduced the expression of cleaved caspase-3, -8, and -9 and the levels of phosphor-protein kinase B (Akt and phosphor-nuclear factor-κB (NF-κB in the liver samples. Collectively, AC-mediated hepatoprotective effects in a mouse model of acute alcohol-induced liver injury are the result of reduction in oxidative stress. This may be associated with Akt/NF-κB signaling. These results provide valuable evidence to support the use of A. cinnamomea as a functional food and/or medicine.

  15. Over-expressing the soluble gp130-Fc does not ameliorate methionine and choline deficient diet-induced non alcoholic steatohepatitis in mice.

    Helene L Kammoun

    Full Text Available Non-alcoholic steatohepatitis (NASH is a liver disease with the potential to lead to cirrhosis and hepatocellular carcinoma. Interleukin-6 (IL-6 has been implicated in the pathogenesis of NASH, with the so-called IL-6 'trans-signaling' cascade being responsible for the pro-inflammatory actions of this cytokine. We aimed to block IL-6 'trans-signaling', using a transgenic mouse that overexpresses human soluble glycoprotein130 (sgp130Fc Tg mice fed a commonly used dietary model of inducing NASH (methionine and choline deficient-diet; MCD diet and hypothesized that markers of NASH would be ameliorated in such mice. Sgp130Fc Tg and littermate control mice were fed a MCD or control diet for 4 weeks. The MCD diet induced many hallmarks of NASH including hepatomegaly, steatosis, and liver inflammation. However, in contrast with other mouse models and, indeed, human NASH, the MCD diet model did not increase the mRNA or protein expression of IL-6. Not surprisingly, therefore, markers of MCD diet-induced NASH were unaffected by sgp130Fc transgenic expression. While the MCD diet model induces many pathophysiological markers of NASH, it does not induce increased IL-6 expression in the liver, a key hallmark of human NASH. We, therefore, caution the use of the MCD diet as a viable mouse model of NASH.

  16. Modulatory role of Co-enzyme Q10 on methionine and choline deficient diet-induced non-alcoholic steatohepatitis (NASH) in albino rats.

    Saleh, Dalia O; Ahmed, Rania F; Amin, Mohamed M

    2017-03-01

    The present study aimed to evaluate the hepato-protective and neuro-protective activity of Co-enzyme Q10 (CoQ10) on non-alcoholic steatohepatitis (NASH) in albino rats induced by methionine and choline-deficient (MCD) diet. Rats were fed an MCD diet for 8 weeks to induce non-alcoholic steatohepatitis. CoQ10 (10 mg/(kg·day) -1 ) was orally administered for 2 consecutive weeks. Twenty-four hours after the last dose of the drug, the behavioral test, namely the activity cage test, was performed and the activity counts were recorded. Serum alanine transaminase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, total/direct bilirubin, and albumin were valued to assess liver function. Moreover, hepatic cytokines interleukin-6 as well as its modulator nuclear factor kappa-light-chain-enhancer of activated B cells were determined. In addition, brain biomarkers, viz ammonia, nitric oxide, and brain-derived neurotrophic factor (BDNF), were measured as they are reliable indices to assess brain damage. Histopathological and immunohistochemical examination of brain proliferating cell nuclear antigen in brain and liver tissues were also evaluated. Results revealed that MCD-induced NASH showed impairment in the liver functions with an increase in the liver inflammatory markers. Moreover, NASH resulted in pronounced brain dysfunction as evidenced by hyper-locomotor activity, a decrease in the BDNF level, as well as an increase in the brain nitric oxide and ammonia contents. Oral treatment of MCD-diet-fed rats with CoQ10 for 14 days showed a marked improvement in all the assigned parameters. Finally, it can be concluded that CoQ10 has a hepatoprotective and neuroprotective role in MCD-diet-induced NASH in rats.

  17. CHRONIC ALCOHOL NEUROADAPTATION AND STRESS CONTRIBUTE TO SUSCEPTIBILITY FOR ALCOHOL CRAVING AND RELAPSE

    BREESE, GEORGE R.; SINHA, RAJITA; HEILIG, MARKUS

    2010-01-01

    Alcoholism is a chronic relapsing disorder. Major characteristics observed in alcoholics during an initial period of alcohol abstinence are altered physiological functions and a negative emotional state. Evidence suggests that a persistent, cumulative adaptation involving a kindling/allostasis-like process occurs during the course of repeated chronic alcohol exposures that is critical for the negative symptoms observed during alcohol withdrawal. Basic studies have provided evidence for specific neurotransmitters within identified brain sites being responsible for the negative emotion induced by the persistent cumulative adaptation following intermittent-alcohol exposures. After an extended period of abstinence, the cumulative alcohol adaptation increases susceptibility to stress- and alcohol cue-induced negative symptoms and alcohol seeking, both of which can facilitate excessive ingestion of alcohol. In the alcoholic, stressful imagery and alcohol cues alter physiological responses, enhance negative emotion, and induce craving. Brain fMRI imaging following stress and alcohol cues has documented neural changes in specific brain regions of alcoholics not observed in social drinkers. Such altered activity in brain of abstinent alcoholics to stress and alcohol cues is consistent with a continuing ethanol adaptation being responsible. Therapies in alcoholics found to block responses to stress and alcohol cues would presumably be potential treatments by which susceptibility for continued alcohol abuse can be reduced. By continuing to define the neurobiological basis of the sustained alcohol adaptation critical for the increased susceptibility of alcoholics to stress and alcohol cues that facilitate craving, a new era is expected to evolve in which the high rate of relapse in alcoholism is minimized. 250 PMID:20951730

  18. γ-radiation-induced degradation of poly(dimethylsilylene-co-methylphenylsilylene) in cyclohexane and THF-ethyl alcohol solution

    Oka, Kunio; Nakao, Ren

    1989-01-01

    γ-Irradiation of high molecular weight poly(dimethylsilylene-co-methyl-phenylsilylene) in cyclohexane and THF-ethyl alcohol solutions was carried out in order to study the degradation mechanism. The G s value (number of chain scissions per 100eV radiation energy absorbed) depends on the dose rate but not on the polysilane concentration. No insertion products of dimethylsilylene or methylphenylsilylene into ethyl alcohol were detected, indicating that no silylene evolution mechanism was involved. IR analysis of the irradiated polymer suggests that chain scission occurs preferentially at the methylphenylsilylene unit. The resulting polysilane (135 Mrad irradiated) has chains of about 20 silicon atoms containing siloxane bonds and hydroxy groups. All of the results indicate that the polysilane degrades by a free radical mechanism. (author)

  19. A Procedure to Observe Context-induced Renewal of Pavlovian-conditioned Alcohol-seeking Behavior in Rats

    Maddux, Jean-Marie; Lacroix, Franca; Chaudhri, Nadia

    2014-01-01

    Environmental contexts in which drugs of abuse are consumed can trigger craving, a subjective Pavlovian-conditioned response that can facilitate drug-seeking behavior and prompt relapse in abstinent drug users. We have developed a procedure to study the behavioral and neural processes that mediate the impact of context on alcohol-seeking behavior in rats. Following acclimation to the taste and pharmacological effects of 15% ethanol in the home cage, male Long-Evans rats receive Pavlovian disc...

  20. Alcohol Advertising

    Trkovská, Jana

    2017-01-01

    The thesis concerns itself with alcohol advertising. Alcohol is the most widespread habit-forming substance, yet its consumption is permitted in most countries all around the world, possibly restricted by the age of consumers only. Drinking alcohol cannot be either regulated or prohibited today. It has become commonplace for the majority of our lives. Being aware of its apparent risks, however, there is an effort to regulate at least alcohol advertising. The main objective of this work was to...

  1. Modification of automatic alcohol-approach tendencies in alcohol-dependent patients with mild or major neurocognitive disorder

    Loijen, A.; Rinck, M.; Walvoort, S.J.W.; Kessels, R.P.C.; Becker, E.S.; Egger, J.I.M.

    2018-01-01

    Background: To examine the applicability of an alcohol-avoidance training procedure in patients with alcohol dependence and alcohol-induced neurocognitive disorders, we trained two groups that differed in the degree of cognitive impairment: One group fulfilled the DSM-5 criteria for Alcohol-Induced

  2. Sida rhomboidea.Roxb extract alleviates pathophysiological changes in experimental in vivo and in vitro models of high fat diet/fatty acid induced non-alcoholic steatohepatitis.

    Thounaojam, Menaka C; Jadeja, Ravirajsinh N; Dandekar, Deven S; Devkar, Ranjitsinh V; Ramachandran, A V

    2012-03-01

    The present study was aim to evaluate protective role of Sida rhomboidea.Roxb (SR) extract against high fat diet/fatty acid induced pathophysiological alterations in experimental model of non-alcoholic steatohepatitis (NASH). Effect of SR extract on plasma levels of markers of hepatic damage, plasma and hepatic lipids, mitochondrial oxidative stress, status of enzymatic and non-enzymatic antioxidants and histopathological changes in liver tissue were evaluated in high fat diet fed C57BL/6J mice. Also, the effect of SR supplementation on lipid accumulation, lipid peroxidation, cytotoxicity and cell viability were evaluated in oleic acid treated HepG2 cells. Supplementation of NASH mice with SR extract prevented high fat diet induced elevation in plasma marker enzymes of liver damage, plasma and hepatic lipids, mitochondrial oxidative stress and compromised enzymatic and non-enzymatic antioxidant status. Further, addition of SR extract to in vitro HepG2 cells minimized oleic acid induced lipid accumulation, higher lipid peroxidation, cytotoxicity and reduced cell viability. These in vivo and in vitro studies suggest that SR extract has the potential of preventing high fat/fatty acid induced NASH mainly due to its hypolipidemic and antioxidant activities. Copyright © 2010 Elsevier GmbH. All rights reserved.

  3. Bee's honey attenuates non-alcoholic steatohepatitis-induced hepatic injury through the regulation of thioredoxin-interacting protein-NLRP3 inflammasome pathway.

    Xiao, Jia; Liu, Yingxia; Xing, Feiyue; Leung, Tung Ming; Liong, Emily C; Tipoe, George L

    2016-06-01

    We aim to examine whether honey ameliorates hepatic injury in non-alcoholic steatohepatitis (NASH) animal and cell line steatosis models. NASH was induced in female Sprague-Dawley rat by 8-week feeding with a high-fat diet. During the experiment, 5 g/kg honey was intragastrically fed daily. Rat normal hepatocyte BRL-3A cell was treated with sodium palmitate (SP) to induce steatosis in the absence or presence of honey pre-treatment or specific siRNA/overexpress plasmid of thioredoxin-interacting protein (TXNIP) or antagonist/agonist of Nod-like receptor protein 3 (NLRP3). Honey significantly improved the high-fat-diet-induced hepatic injury, steatosis, fibrosis, oxidative stress, and inflammation in rats. Honey also inhibited the overexpression of TXNIP and the activation of NLRP3 inflammasome. These effects were replicated in BRL-3A cell line which showed that the down-regulation of TXNIP or inhibition of NLRP3 contributed to the suppression of NLRP3 inflammasome activation, inflammation, and re-balanced lipid metabolism. In contrast, overexpression of TXNIP or agonism of NLRP3 exacerbated the cellular damage induced by SP. Suppression of the TXNIP-NLRP3 inflammasome pathway may partly contribute to the amelioration of hepatic injury during the progression of NASH by honey. Targeting hepatic TXNIP-NLRP3 inflammasome pathway is a potential therapeutic way for the prevention and treatment of NASH.

  4. MRI study of the cuprizone-induced mouse model of multiple sclerosis: demyelination is not found after co-treatment with polyprenols (long-chain isoprenoid alcohols)

    Khodanovich, M.; Glazacheva, V.; Pan, E.; Akulov, A.; Krutenkova, E.; Trusov, V.; Yarnykh, V.

    2016-02-01

    Multiple sclerosis is a neurological disorder with poorly understood pathogenic mechanisms and a lack of effective therapies. Therefore, the search for new MS treatments remains very important. This study was performed on a commonly used cuprizone animal model of multiple sclerosis. It evaluated the effect of a plant-derived substance called Ropren® (containing approximately 95% polyprenols or long-chain isoprenoid alcohols) on cuprizone- induced demyelination. The study was performed on 27 eight-week old male CD-1 mice. To induce demyelination mice were fed 0.5% cuprizone in the standard diet for 10 weeks. Ropren® was administered in one daily intraperitoneal injection (12mg/kg), beginning on the 6th week of the experiment. On the 11th week, the corpus callosum in the brain was evaluated in all animals using magnetic resonance imaging with an 11.7 T animal scanner using T2- weighted sequence. Cuprizone treatment successfully induced the model of demyelination with a significant decrease in the size of the corpus callosum compared with the control group (p<0.01). Mice treated with both cuprizone and Ropren® did not exhibit demyelination in the corpus callosum (p<0.01). This shows the positive effect of polyprenols on cuprizone-induced demyelination in mice.

  5. Dietary capsaicin and antibiotics act synergistically to reduce non-alcoholic fatty liver disease induced by high fat diet in mice.

    Hu, Jingjuan; Luo, Haihua; Jiang, Yong; Chen, Peng

    2017-06-13

    The prevalence of non-alcoholic fatty liver disease is increasing rapidly worldwide. However, effective strategies for combating high-fat diet (HFD) induced obesity, fatty liver and metabolic disorder are still limited, and outcomes remain poor. In the present study, we evaluated the combined actions of dietary capsaicin and antibiotics on HFD-induced physiological abnormalities in mice. C57BL/6 male mice were fed with HFD (60% calories from fat) for 17 weeks, and the resultant pathophysiological effects were examined. Antibiotic treatment markedly attenuated gut inflammation and leakiness induced by HFD, whereas capsaicin showed limited effects on the gut. However, dietary capsaicin significantly increased PPAR-α expression in adipose tissue, while antibiotics had no such effect. Animals treated with a combination of capsaicin and antibiotics had the smallest body weight gain and fat pad index, as well as the lowest hepatic fat accumulation. Combination treatment also maximally improved insulin responsiveness, as indicated by insulin tolerance tests. These results suggest the co-treatment of capsaicin and antibiotics, a novel combination strategy, would play synergistically to attenuate the HFD-induced obesity, fatty liver and metabolic disorder.

  6. CvADH1, a member of short-chain alcohol dehydrogenase family, is inducible by gibberellin and sucrose in developing watermelon seeds.

    Kim, Joonyul; Kang, Hong-Gyu; Jun, Sung-Hoon; Lee, Jinwon; Yim, Jieun; An, Gynheung

    2003-01-01

    To understand the molecular mechanisms that control seed formation, we selected a seed-preferential gene (CvADH1) from the ESTs of developing watermelon seeds. RNA blot analysis and in situ localization showed that CvADH1 was preferentially expressed in the nucellar tissue. The CvADH1 protein shared about 50% homology with short-chain alcohol dehydrogenase including ABA2 in Arabidopsis thaliana, stem secoisolariciresinol dehydrogenase in Forsythia intermedia, and 3beta-hydroxysterol dehydrogenase in Digitalis lanata. We investigated gene-expression levels in seeds from both normally pollinated fruits and those made parthenocarpic via N-(2-chloro-4-pyridyl)-N'-phenylurea treatment, the latter of which lack zygotic tissues. Whereas the transcripts of CvADH1 rapidly started to accumulate from about the pre-heart stage in normal seeds, they were not detectable in the parthenocarpic seeds. Treating the parthenogenic fruit with GA(3) strongly induced gene expression, up to the level accumulated in pollinated seeds. These results suggest that the CvADH1 gene is induced in maternal tissues by signals made in the zygotic tissues, and that gibberellin might be one of those signals. We also observed that CvADH1 expression was induced by sucrose in the parthenocarpic seeds. Therefore, we propose that the CvADH1 gene is inducible by gibberellin, and that sucrose plays an important role in the maternal tissues of watermelon during early seed development.

  7. Adriamycin-induced oxidative stress is prevented by mixed hydro-alcoholic extract of Nigella sativa and Curcuma longa in rat kidney.

    Mohebbati, Reza; Shafei, Mohammad Naser; Soukhtanloo, Mohammad; Mohammadian Roshan, Noema; Khajavi Rad, Abolfazl; Anaeigoudari, Akbar; Hosseinian, Sara; Karimi, Sareh; Beheshti, Farimah

    2016-01-01

    Inflammation and oxidative stress is considered to have a crucial role in induction of nephropathy. Curcuma longa (C. longa) and Nigella sativa (N. sativa) have anti-inflammatory and antioxidant effects. This study was designed to investigate the effect of mixed hydro-alcoholic extract of N.sativa and C. longa on the oxidative stress induced by Adriamycin (ADR) in rat kidney. The animals were divided into 6 groups: control (CO), ADR, Adriamycin+ Vitamin C (ADR+VIT C), C. longa extract+ Adriamycin (C.LE+ADR), N. sativa extract+ Adriamycin (N.SE+ADR) and C. longa extract+ N. sativa extract + Adriamycin (N.S+C.L+ADR). ADR (5mg/kg) was injected intravenously, whereas VITC (100mg/kg) and extract of C. longa (1000mg/kg) and N. sativa (200mg/kg) were administrated orally. Finally, the renal tissue, urine and blood samples were collected and submitted to measure of redox markers, osmolarity and renal index. The renal content of total thiol and superoxide dismutase (SOD) activity significantly decreased and Malondialdehyde (MDA) concentration increased in Adriamycin group compared to control group. The renal content of total thiol and SOD activity significantly enhanced and MDA concentration reduced in treated-mixed extract of C. longa and N. sativa along with ADR group compared to ADR group. The mixed extract did not restore increased renal index percentage induced by ADR. There also was no significant difference in urine and serum osmolarity between the groups. hydro-alcoholic extracts of N.sativa and C.longa led to an improvement in ADR-induced oxidative stress and mixed administration of the extracts enhanced the aforementioned therapeutic effect.

  8. The Difference between Anxiolytic and Anxiogenic Effects Induced by Acute and Chronic Alcohol Exposure and Changes in Associative Learning and Memory Based on Color Preference and the Cause of Parkinson-Like Behaviors in Zebrafish.

    Xiang Li

    Full Text Available We describe an interdisciplinary comparison of the effects of acute and chronic alcohol exposure in terms of their disturbance of light, dark and color preferences and the occurrence of Parkinson-like behavior in zebrafish through computer visual tracking, data mining, and behavioral and physiological analyses. We found that zebrafish in anxiolytic and anxious states, which are induced by acute and chronic repeated alcohol exposure, respectively, display distinct emotional reactions in light/dark preference tests as well as distinct learning and memory abilities in color-enhanced conditional place preference (CPP tests. Additionally, compared with the chronic alcohol (1.0% treatment, acute alcohol exposure had a significant, dose-dependent effect on anxiety, learning and memory (color preference as well as locomotive activities. Acute exposure doses (0.5%, 1.0%, and 1.5% generated an "inverted V" dose-dependent pattern in all of the behavioral parameters, with 1.0% having the greatest effect, while the chronic treatment had a moderate effect. Furthermore, by measuring locomotive activity, learning and memory performance, the number of dopaminergic neurons, tyrosine hydroxylase expression, and the change in the photoreceptors in the retina, we found that acute and chronic alcohol exposure induced varying degrees of Parkinson-like symptoms in zebrafish. Taken together, these results illuminated the behavioral and physiological mechanisms underlying the changes associated with learning and memory and the cause of potential Parkinson-like behaviors in zebrafish due to acute and chronic alcohol exposure.

  9. The Difference between Anxiolytic and Anxiogenic Effects Induced by Acute and Chronic Alcohol Exposure and Changes in Associative Learning and Memory Based on Color Preference and the Cause of Parkinson-Like Behaviors in Zebrafish.

    Li, Xiang; Li, Xu; Li, Yi-Xiang; Zhang, Yuan; Chen, Di; Sun, Ming-Zhu; Zhao, Xin; Chen, Dong-Yan; Feng, Xi-Zeng

    2015-01-01

    We describe an interdisciplinary comparison of the effects of acute and chronic alcohol exposure in terms of their disturbance of light, dark and color preferences and the occurrence of Parkinson-like behavior in zebrafish through computer visual tracking, data mining, and behavioral and physiological analyses. We found that zebrafish in anxiolytic and anxious states, which are induced by acute and chronic repeated alcohol exposure, respectively, display distinct emotional reactions in light/dark preference tests as well as distinct learning and memory abilities in color-enhanced conditional place preference (CPP) tests. Additionally, compared with the chronic alcohol (1.0%) treatment, acute alcohol exposure had a significant, dose-dependent effect on anxiety, learning and memory (color preference) as well as locomotive activities. Acute exposure doses (0.5%, 1.0%, and 1.5%) generated an "inverted V" dose-dependent pattern in all of the behavioral parameters, with 1.0% having the greatest effect, while the chronic treatment had a moderate effect. Furthermore, by measuring locomotive activity, learning and memory performance, the number of dopaminergic neurons, tyrosine hydroxylase expression, and the change in the photoreceptors in the retina, we found that acute and chronic alcohol exposure induced varying degrees of Parkinson-like symptoms in zebrafish. Taken together, these results illuminated the behavioral and physiological mechanisms underlying the changes associated with learning and memory and the cause of potential Parkinson-like behaviors in zebrafish due to acute and chronic alcohol exposure.

  10. Alcoholic fermentation

    Colin, P

    1961-01-04

    The addition of C/sub 6-10/ alcohols to the fermenting sugar solutions, increased the yield of alcohol by 1.5 to 5%. The best additives were (additive, % additive in sugar solution, % increased in yield of alcohol): hexanol, 0.03, 2.5; heptanol, 0.05, 3; nonanol, 0.01, 3; 2-ethylbutanol, 0.05, 4; 2-ethylhexanol, 0.05, 5; a mixture of C/sub 7-9/ alcohols from the Oxo synthesis, 0.05, 4.5, and a mixture of C/sub 10/ alcohols 0.05, 3.

  11. Disruption of adherens junction and alterations in YAP-related proliferation behavior as part of the underlying cell transformation process of alcohol-induced oral carcinogenesis.

    Husari, Ayman; Hülter-Hassler, Diana; Steinberg, Thorsten; Schulz, Simon Daniel; Tomakidi, Pascal

    2018-01-01

    Accumulating evidences indicate that alcohol might play a causative in oral cancer. Unfortunately, in vitro cell systems, uncovering the molecular background of the underlying cell transformation process, are rare. Therefore, this study was conducted, to identify molecular changes and characterize their putative cell behavioral consequences in epitheloid (EPI) and fibroblastoid (FIB) oral keratinocyte phenotypes, arising from chronical alcohol treatment. Concerning adherens junctions (AJs), both EPI and FIB showed membrane-bound β-catenin, but exhibited differences for E-cadherin and zyxin. While EPI revealed E-cadherin/β-catenin membrane co-localization, which in parts also applied for zyxin, FIB membranes were devoid of E-cadherin and exhibited marginal zyxin expression. Fetal calf serum (FCS) administration in starved cells promoted proliferation in both keratinocyte phenotypes, whereat EPI and FIB yielded a strikingly modified FCS sensitivity on the temporal scale. Impedance measurement-based cell index detection yielded proliferation stimulation occurring much earlier in FIB (45h). Nuclear preference of the proliferation-associated YAP co-transcription factor in FIB was FCS independent, while it required FCS in EPI. Taken together, the lack of membrane-inherent E-cadherin/β-catenin co-localization together with low zyxin - reveals perturbation of AJ integrity in FIB. Regarding cell behavior, perturbed AJs in FIB correlate with temporal proliferation sensitivity towards FCS. CYF of 5.6 strongly suggests involvement of chromatin-bound YAP in FIB's proliferation temperosensitivity. These molecular differences detected for EPI and FIB are part of the underlying cell transformation process of alcohol-induced oral carcinogenesis, and indicate FIB being in a more advanced transformation stage. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Social defeat promotes a reactive endothelium in a brain region-dependent manner with increased expression of key adhesion molecules, selectins and chemokines associated with the recruitment of myeloid cells to the brain.

    Sawicki, C M; McKim, D B; Wohleb, E S; Jarrett, B L; Reader, B F; Norden, D M; Godbout, J P; Sheridan, J F

    2015-08-27

    Repeated social defeat (RSD) in mice causes myeloid cell trafficking to the brain that contributes to the development of prolonged anxiety-like behavior. Myeloid cell recruitment following RSD occurs in regions where neuronal and microglia activation is observed. Thus, we hypothesized that crosstalk between neurons, microglia, and endothelial cells contributes to brain myeloid cell trafficking via chemokine signaling and vascular adhesion molecules. Here we show that social defeat caused an exposure- and brain region-dependent increase in several key adhesion molecules and chemokines involved in the recruitment of myeloid cells. For example, RSD induced distinct patterns of adhesion molecule expression that may explain brain region-dependent myeloid cell trafficking. VCAM-1 and ICAM-1 mRNA expression were increased in an exposure-dependent manner. Furthermore, RSD-induced VCAM-1 and ICAM-1 protein expression were localized to the vasculature of brain regions implicated in fear and anxiety responses, which spatially corresponded to previously reported patterns of myeloid cell trafficking. Next, mRNA expression of additional adhesion molecules (E- and P-selectin, PECAM-1) and chemokines (CXCL1, CXCL2, CXCL12, CCL2) were determined in the brain. Social defeat induced an exposure-dependent increase in mRNA levels of E-selectin, CXCL1, and CXCL2 that increased with additional days of social defeat. While CXCL12 was unaffected by RSD, CCL2 expression was increased by six days of social defeat. Last, comparison between enriched CD11b(+) cells (microglia/macrophages) and enriched GLAST-1(+)/CD11b(-) cells (astrocytes) revealed RSD increased mRNA expression of IL-1β, CCL2, and CXCL2 in microglia/macrophages but not in astrocytes. Collectively, these data indicate that key mediators of leukocyte recruitment were increased in the brain vasculature following RSD in an exposure- and brain region-dependent manner. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights

  13. Exploring the molecular mechanisms underlying the potentiation of exogenous growth hormone on alcohol-induced fatty liver diseases in mice

    Tian Ya-ping

    2010-11-01

    Full Text Available Abstract Background Growth hormone (GH is an essential regulator of intrahepatic lipid metabolism by activating multiple complex hepatic signaling cascades. Here, we examined whether chronic exogenous GH administration (via gene therapy could ameliorate liver steatosis in animal models of alcoholic fatty liver disease (AFLD and explored the underlying molecular mechanisms. Methods Male C57BL/6J mice were fed either an alcohol or a control liquid diet with or without GH therapy for 6 weeks. Biochemical parameters, liver histology, oxidative stress markers, and serum high molecular weight (HMW adiponectin were measured. Quantitative real-time PCR and western blotting were also conducted to determine the underlying molecular mechanism. Results Serum HMW adiponectin levels were significantly higher in the GH1-treated control group than in the control group (3.98 ± 0.71 μg/mL vs. 3.07 ± 0.55 μg/mL; P P P P P Conclusions GH therapy had positive effects on AFLD and may offer a promising approach to prevent or treat AFLD. These beneficial effects of GH on AFLD were achieved through the activation of the hepatic adiponectin-SIRT1-AMPK and PPARα-AMPK signaling systems.

  14. The effect of hydro-alcoholic celery (Apium graveolens leaf extract on cardiovascular parameters and lipid profile in animal model of hypertension induced by fructose

    Mahin Dianat

    2015-04-01

    Full Text Available Objectives:Hypertension is one of the most common diseases of the modern era. This study evaluates the effect of hydro-alcoholic celery leaf extract onsystolic blood pressure (SBP, heart rate (HR and lipid profile in animals’ model of hypertension induced by fructose. Materials and Methods: Sprague Dawley rats were divided into five groups: 1 control group (free access to tap drinking water, 2 group receiving 200mg/kg celery leaf extract, 3 group receiving fructose 10%, and 4,5 receiving fructose and 100mg/kg or 200mg/kg of extract (n=8. In all groups, before and during the test period, SBP and HR were measured by Power lab system. Lipid profiles were determined by auto analysis. Repeated measurement and one way ANOVA were used for data analysis. PResults:The SBP in the fructose group significantly increased compared to control group (P

  15. Antihypertensive Effect of Radix Paeoniae Alba in Spontaneously Hypertensive Rats and Excessive Alcohol Intake and High Fat Diet Induced Hypertensive Rats

    Chen Su-Hong

    2015-01-01

    Full Text Available Radix Paeoniae Alba (Baishao, RPA has long been used in traditional Chinese medicine formulation to treat hypertension by repression the hyperfunction of liver. However, whether the RPA itself has the antihypertensive effect or not is seldom studied. This study was to evaluate the protective effect of RPA on hypertensive rats. Alcohol in conjunction with a high fat diet- (ACHFD- induced hypertensive rats and spontaneously hypertensive rats (SHR was constantly received either RPA extract (25 or 75 mg/kg or captopril (15 mg/kg all along the experiments. As a result, RPA extract (75 mg/kg could significantly reduce systolic blood pressure of both ACHFD-induced hypertensive rats and SHR after 9-week or 4-week treatment. In ACHFD-induced hypertensive rats, the blood pressure was significantly increased and the lipid profiles in serum including triglyceride, total cholesterol, LDL-cholesterol, and HDL-cholesterol were significantly deteriorated. Also, hepatic damage was manifested by a significant increase in alanine transaminase (ALT and aspartate transaminase (AST in serum. The RPA extract significantly reversed these parameters, which revealed that it could alleviate the liver damage of rats. In SHR, our result suggested that the antihypertensive active of RPA extract may be related to its effect on regulating serum nitric oxide (NO and endothelin (ET levels.

  16. Sex-specific metabolic interactions between liver and adipose tissue in MCD diet-induced non-alcoholic fatty liver disease.

    Lee, Yun-Hee; Kim, Sou Hyun; Kim, Sang-Nam; Kwon, Hyun-Jung; Kim, Jeong-Dong; Oh, Ji Youn; Jung, Young-Suk

    2016-07-26

    Higher susceptibility to metabolic disease in male exemplifies the importance of sexual dimorphism in pathogenesis. We hypothesized that the higher incidence of non-alcoholic fatty liver disease in males involves sex-specific metabolic interactions between liver and adipose tissue. In the present study, we used a methionine-choline deficient (MCD) diet-induced fatty liver mouse model to investigate sex differences in the metabolic response of the liver and adipose tissue. After 2 weeks on an MCD-diet, fatty liver was induced in a sex-specific manner, affecting male mice more severely than females. The MCD-diet increased lipolytic enzymes in the gonadal white adipose tissue (gWAT) of male mice, whereas it increased expression of uncoupling protein 1 and other brown adipocyte markers in the gWAT of female mice. Moreover, gWAT from female mice demonstrated higher levels of oxygen consumption and mitochondrial content compared to gWAT from male mice. FGF21 expression was increased in liver tissue by the MCD diet, and the degree of upregulation was significantly higher in the livers of female mice. The endocrine effect of FGF21 was responsible, in part, for the sex-specific browning of gonadal white adipose tissue. Collectively, these data demonstrated that distinctively female-specific browning of white adipose tissue aids in protecting female mice against MCD diet-induced fatty liver disease.

  17. Complement and alcoholic liver disease: role of C1q in the pathogenesis of ethanol-induced liver injury in mice.

    Cohen, Jessica I; Roychowdhury, Sanjoy; McMullen, Megan R; Stavitsky, Abram B; Nagy, Laura E

    2010-08-01

    Complement is involved in the development of alcoholic liver disease in mice; however, the mechanisms for complement activation during ethanol exposure have not been identified. C1q, the recognition subunit of the first complement component, binds to apoptotic cells, thereby activating the classical complement pathway. Because ethanol exposure increases hepatocellular apoptosis, we hypothesized that ethanol-induced apoptosis would lead to activation of complement via the classical pathway. Wild-type and C1qa-/- mice were allowed free access to ethanol-containing diets or pair-fed control diets for 4 or 25 days. Ethanol feeding for 4 days increased apoptosis of Kupffer cells in both wild-type and C1qa-/- mice. Ethanol-induced deposition of C1q and C3b/iC3b/C3c was colocalized with apoptotic Kupffer cells in wild-type, but not C1qa-/-, mice. Furthermore, ethanol-induced increases in tumor necrosis factor-alpha and interleukin-6 expression at this early time point were suppressed in C1q-deficient mice. Chronic ethanol feeding (25 days) increased steatosis, hepatocyte apoptosis, and activity of serum alanine and aspartate aminotransferases in wild-type mice. These markers of hepatocyte injury were attenuated in C1qa-/- mice. In contrast, chronic ethanol (25 days)-induced increases in cytochrome P450 2E1 expression and oxidative stress did not differ between wild-type and C1qa-/- mice. For the first time, these data indicate that ethanol activates the classical complement pathway via C1q binding to apoptotic cells in the liver and that C1q contributes to the pathogenesis of ethanol-induced liver injury. Copyright (c) 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

  18. Regulation of a Glycerol-Induced Quinoprotein Alcohol Dehydrogenase by σ54 and a LuxR-Type Regulator in Azospirillum brasilense Sp7.

    Singh, Vijay Shankar; Dubey, Ashutosh Prakash; Gupta, Ankush; Singh, Sudhir; Singh, Bhupendra Narain; Tripathi, Anil Kumar

    2017-07-01

    Azospirillum brasilense Sp7 uses glycerol as a carbon source for growth and nitrogen fixation. When grown in medium containing glycerol as a source of carbon, it upregulates the expression of a protein which was identified as quinoprotein alcohol dehydrogenase (ExaA). Inactivation of exaA adversely affects the growth of A. brasilense on glycerol. A determination of the transcription start site of exaA revealed an RpoN-dependent -12/-24 promoter consensus. The expression of an exaA :: lacZ fusion was induced maximally by glycerol and was dependent on σ 54 Bioinformatic analysis of the sequence flanking the -12/-24 promoter revealed a 17-bp sequence motif with a dyad symmetry of 6 nucleotides upstream of the promoter, the disruption of which caused a drastic reduction in promoter activity. The electrophoretic mobility of a DNA fragment containing the 17-bp sequence motif was retarded by purified EraR, a LuxR-type transcription regulator that is transcribed divergently from exaA EraR also showed a positive interaction with RpoN in two-hybrid and pulldown assays. IMPORTANCE Quinoprotein alcohol dehydrogenase (ExaA) plays an important role in the catabolism of alcohols in bacteria. Although exaA expression is thought to be regulated by a two-component system consisting of EraS and EraR, the mechanism of regulation was not known. This study shows the details of the regulation of expression of the exaA gene in A. brasilense We have shown here that exaA of A. brasilense is maximally induced by glycerol and harbors a σ 54 -dependent promoter. The response regulator EraR binds to an inverted repeat located upstream of the exaA promoter. This study shows that a LuxR-type response regulator (EraR) binds upstream of the exaA gene and physically interacts with σ 54 The unique feature of this regulation is that EraR is a LuxR-type transcription regulator that lacks the GAFTGA motif, a characteristic feature of the enhancer binding proteins that are known to interact with σ 54

  19. Effects of Hydro-alcoholic Extract from Arctium lappa L. (Burdock) Root on Gonadotropins, Testosterone, and Sperm Count and Viability in Male Mice with Nicotinamide/ Streptozotocin-Induced Type 2 Diabetes

    AHANGARPOUR, Akram; OROOJAN, Ali Akbar; HEIDARI, Hamid; GHAEDI, Ehsan; TAHERKHANI, Reza

    2015-01-01

    Background: Reproductive dysfunction is a complication of diabetes. Arctium lappa (burdock) root has hypoglycemic and antioxidative properties, which are traditionally used for treatment of impotence and sterility. Therefore, the aim of this study is to investigate the effects of its hydro alcoholic extract on gonadotropin, testosterone, and sperm parameters in nicotinamide/ streptozotocin-induced diabetic mice.

  20. Docosahexaenoic acid prevents trans-10, cis-12 conjugated linoleic acid-induced non-alcoholic fatty liver disease in mice by altering expression of hepatic genes regulating fatty acid synthesis and oxidation

    Background: Concomitant supplementation with docosahexaenoic acid (22:6 n-3; DHA) prevented t10, c12- conjugated linoleic acid (CLA)-induced non-alcoholic fatty liver disease (NAFLD) and insulin resistance. Effective dose of DHA and mechanisms involved are poorly understood. Methods: We examined abi...

  1. Evaluation of Aroclor 1260 exposure in a mouse model of diet-induced obesity and non-alcoholic fatty liver disease

    Wahlang, Banrida; Song, Ming; Beier, Juliane I.; Cameron Falkner, K.; Al-Eryani, Laila; Clair, Heather B.; Prough, Russell A.; Osborne, Tanasa S.; Malarkey, David E.; Christopher States, J.; Cave, Matthew C.

    2014-01-01

    Polychlorinated biphenyls (PCBs) are persistent organic pollutants associated with non-alcoholic fatty liver disease (NAFLD) in epidemiologic studies. The purpose of this study was to evaluate the hepatic effects of a PCB mixture, Aroclor 1260, whose composition mimics human bioaccumulation patterns, in a mouse model of diet-induced obesity (DIO). Male C57Bl/6J mice were fed control diet or 42% high fat diet (HFD) and exposed to Aroclor 1260 (20 mg/kg or 200 mg/kg in corn oil) for 12 weeks. A glucose tolerance test was performed; plasma/tissues were obtained at necropsy for measurements of adipocytokine levels, histology, and gene expression. Aroclor 1260 exposure was associated with decreased body fat in HFD-fed mice but had no effect on blood glucose/lipid levels. Paradoxically, Aroclor 1260 + HFD co-exposed mice demonstrated increased hepatic inflammatory foci at both doses while the degree of steatosis did not change. Serum cytokines, ALT levels and hepatic expression of IL-6 and TNFα were increased only at 20 mg/kg, suggesting an inhibition of pro-inflammatory cytokine production at the 200 mg/kg exposure. Aroclor 1260 induced hepatic expression of cytochrome P450s including Cyp3a11 (Pregnane-Xenobiotic Receptor target) and Cyp2b10 (constitutive androstane receptor target) but Cyp2b10 inducibility was diminished with HFD-feeding. Cyp1a2 (aryl hydrocarbon Receptor target) was induced only at 200 mg/kg. In summary, Aroclor 1260 worsened hepatic and systemic inflammation in DIO. The results indicated a bimodal response of PCB-diet interactions in the context of inflammation which could potentially be explained by xenobiotic receptor activation. Thus, PCB exposure may be a relevant “second hit” in the transformation of steatosis to steatohepatitis. - Highlights: • Aroclor 1260 exposure decreased adiposity in mice fed with high fat diet • Aroclor 1260 exposure induced steatohepatitis in diet-induced obese mice • Aroclor 1260 (20 and 200 mg/kg) induced

  2. Evaluation of Aroclor 1260 exposure in a mouse model of diet-induced obesity and non-alcoholic fatty liver disease

    Wahlang, Banrida [Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202 (United States); Song, Ming [Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville School of Medicine, Louisville, KY 40202 (United States); Beier, Juliane I. [Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202 (United States); Cameron Falkner, K. [Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville School of Medicine, Louisville, KY 40202 (United States); Al-Eryani, Laila [Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202 (United States); Clair, Heather B.; Prough, Russell A. [Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, Louisville, KY 40202 (United States); Osborne, Tanasa S.; Malarkey, David E. [Cellular and Molecular Pathology Branch, National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 (United States); Christopher States, J. [Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202 (United States); Cave, Matthew C., E-mail: matt.cave@louisville.edu [Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202 (United States); Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville School of Medicine, Louisville, KY 40202 (United States); The Robley Rex Veterans Affairs Medical Center, Louisville, KY 40206 (United States)

    2014-09-15

    Polychlorinated biphenyls (PCBs) are persistent organic pollutants associated with non-alcoholic fatty liver disease (NAFLD) in epidemiologic studies. The purpose of this study was to evaluate the hepatic effects of a PCB mixture, Aroclor 1260, whose composition mimics human bioaccumulation patterns, in a mouse model of diet-induced obesity (DIO). Male C57Bl/6J mice were fed control diet or 42% high fat diet (HFD) and exposed to Aroclor 1260 (20 mg/kg or 200 mg/kg in corn oil) for 12 weeks. A glucose tolerance test was performed; plasma/tissues were obtained at necropsy for measurements of adipocytokine levels, histology, and gene expression. Aroclor 1260 exposure was associated with decreased body fat in HFD-fed mice but had no effect on blood glucose/lipid levels. Paradoxically, Aroclor 1260 + HFD co-exposed mice demonstrated increased hepatic inflammatory foci at both doses while the degree of steatosis did not change. Serum cytokines, ALT levels and hepatic expression of IL-6 and TNFα were increased only at 20 mg/kg, suggesting an inhibition of pro-inflammatory cytokine production at the 200 mg/kg exposure. Aroclor 1260 induced hepatic expression of cytochrome P450s including Cyp3a11 (Pregnane-Xenobiotic Receptor target) and Cyp2b10 (constitutive androstane receptor target) but Cyp2b10 inducibility was diminished with HFD-feeding. Cyp1a2 (aryl hydrocarbon Receptor target) was induced only at 200 mg/kg. In summary, Aroclor 1260 worsened hepatic and systemic inflammation in DIO. The results indicated a bimodal response of PCB-diet interactions in the context of inflammation which could potentially be explained by xenobiotic receptor activation. Thus, PCB exposure may be a relevant “second hit” in the transformation of steatosis to steatohepatitis. - Highlights: • Aroclor 1260 exposure decreased adiposity in mice fed with high fat diet • Aroclor 1260 exposure induced steatohepatitis in diet-induced obese mice • Aroclor 1260 (20 and 200 mg/kg) induced

  3. Alcohol Dehydrogenase Protects against Endoplasmic Reticulum Stress-Induced Myocardial Contractile Dysfunction via Attenuation of Oxidative Stress and Autophagy: Role of PTEN-Akt-mTOR Signaling.

    Jiaojiao Pang

    Full Text Available The endoplasmic reticulum (ER plays an essential role in ensuring proper folding of the newly synthesized proteins. Aberrant ER homeostasis triggers ER stress and development of cardiovascular diseases. ADH is involved in catalyzing ethanol to acetaldehyde although its role in cardiovascular diseases other than ethanol metabolism still remains elusive. This study was designed to examine the impact of ADH on ER stress-induced cardiac anomalies and underlying mechanisms involved using cardiac-specific overexpression of alcohol dehydrogenase (ADH.ADH and wild-type FVB mice were subjected to the ER stress inducer tunicamycin (1 mg/kg, i.p., for 48 hrs. Myocardial mechanical and intracellular Ca(2+ properties, ER stress, autophagy and associated cell signaling molecules were evaluated.ER stress compromised cardiac contractile function (evidenced as reduced fractional shortening, peak shortening, maximal velocity of shortening/relengthening, prolonged relengthening duration and impaired intracellular Ca(2+ homeostasis, oxidative stress and upregulated autophagy (increased LC3B, Atg5, Atg7 and p62, along with dephosphorylation of PTEN, Akt and mTOR, all of which were attenuated by ADH. In vitro study revealed that ER stress-induced cardiomyocyte anomaly was abrogated by ADH overexpression or autophagy inhibition using 3-MA. Interestingly, the beneficial effect of ADH was obliterated by autophagy induction, inhibition of Akt and mTOR. ER stress also promoted phosphorylation of the stress signaling ERK and JNK, the effect of which was unaffected by ADH transgene.Taken together, these findings suggested that ADH protects against ER stress-induced cardiac anomalies possibly via attenuation of oxidative stress and PTEN/Akt/mTOR pathway-regulated autophagy.

  4. The Biphasic Effects of Moderate Alcohol Consumption with a Meal on Ambiance-Induced Mood and Autonomic Nervous System Balance : A Randomized Crossover Trial

    Schrieks, I.C.; Stafleu, A.; Kallen, V.L.; Grootjen, M.; Witkamp, R.F.; Hendriks, H.F.J.

    2014-01-01

    Background: The pre-drinking mood state has been indicated to be an important factor in the mood effects of alcohol. However, for moderate alcohol consumption there are no controlled studies showing this association. Also, the mood effects of consuming alcohol combined with food are largely unknown.

  5. Molecular mechanisms of synaptic remodeling in alcoholism.

    Kyzar, Evan J; Pandey, Subhash C

    2015-08-05

    Alcohol use and alcohol addiction represent dysfunctional brain circuits resulting from neuroadaptive changes during protracted alcohol exposure and its withdrawal. Alcohol exerts a potent effect on synaptic plasticity and dendritic spine formation in specific brain regions, providing a neuroanatomical substrate for the pathophysiology of alcoholism. Epigenetics has recently emerged as a critical regulator of gene expression and synaptic plasticity-related events in the brain. Alcohol exposure and withdrawal induce changes in crucial epigenetic processes in the emotional brain circuitry (amygdala) that may be relevant to the negative affective state defined as the "dark side" of addiction. Here, we review the literature concerning synaptic plasticity and epigenetics, with a particular focus on molecular events related to dendritic remodeling during alcohol abuse and alcoholism. Targeting epigenetic processes that modulate synaptic plasticity may yield novel treatments for alcoholism. Published by Elsevier Ireland Ltd.

  6. CEREBRAL CORTEX DAMAGE INDUCED BY ACUTE ORAL ...

    2018-02-28

    Feb 28, 2018 ... This study examines alcohol-induced cerebral cortex damage and the association with oxidative ... alcohol has profound effects on the function ... Chronic use of ..... Alcohol induced brain damage and liver damage in young.

  7. Alcohol depletes coenzyme-Q10 associated with increased TNF-alpha secretion to induce cytotoxicity in HepG2 cells

    Vidyashankar, Satyakumar; Nandakumar, Krishna S.; Patki, Pralhad S.

    2012-01-01

    Highlights: ► Ethanol induced cytotoxicity in HepG2 cells in absence of lipogenesis. ► Ethanol inhibited HMG-CoA reductase activity. ► Ethanol induced HMG-CoA reductase inhibition is due to decreased cell viability. ► Incubation with mevalonate could not increase the cholesterol. ► Cytotoxicity brought about by CoQ10 depletion and increased TNF-alpha. -- Abstract: Alcohol consumption has been implicated to cause severe hepatic steatosis which is mediated by alcohol dehydrogenase (ADH) activity and CYP 450 2E1 expression. In this context, the effect of ethanol was studied for its influence on lipogenesis in HepG2 cell which is deficient of ADH and does not express CYP 450 2E1. The results showed that ethanol at 100 mM concentration caused 40% cytotoxicity at 72 h as determined by MTT assay. The incorporation of labeled [2- 14 C] acetate into triacylglycerol and phospholipid was increased by 40% and 26% respectively upon 24 h incubation, whereas incorporation of labeled [2- 14 C] acetate into cholesterol was not significantly increased. Further, ethanol inhibited HMG-CoA reductase which is a rate-limiting enzyme in the cholesterol biosynthesis. It was observed that, HMG-CoA reductase inhibition was brought about by ethanol as a consequence of decreased cell viability, since incubation of HepG2 cells with mevalonate could not increase the cholesterol content and increase the cell viability. Addition of ethanol significantly increased TNF-alpha secretion and depleted mitochondrial coenzyme-Q 10 which is detrimental for cell viability. But vitamin E (10 mM) could partially restore coenzyme-Q 10 and glutathione content with decreased TNF-alpha secretion in ethanol treated cells. Further, lipid peroxidation, glutathione peroxidase and superoxide dismutase enzyme activities remained unaffected. Ethanol decreased glutathione content while, GSH/GSSG ratio was significantly higher compared to other groups showing cellular pro-oxidant and antioxidant balance remained

  8. Titanium carbide nanocube core induced interfacial growth of crystalline polypyrrole/polyvinyl alcohol lamellar shell for wide-temperature range supercapacitors

    Weng, Yu-Ting; Pan, Hsiao-An; Wu, Nae-Lih; Chen, Geroge Zheng

    2015-01-01

    This is the first investigation on electrically conducting polymers-based supercapacitor electrodes over a wide temperature range, from -18 °C to 60 °C. A high-performance supercapacitor electrode material consisting of TiC nanocube core and conformal crystalline polypyrrole (PPy)/poly-vinyl-alcohol (PVA) lamellar shell has been synthesized by heterogeneous nucleation-induced interfacial crystallization. PPy is induced to crystallize on the negatively charged TiC nanocube surfaces via strong interfacial interactions. In this organic-inorganic hybrid nanocomposite, the long chain PVA enables enhanced cycle life due to improved mechanical properties, and the TiC nanocube not only contributes to electron conduction, but also dictates the PPy morphology/crystallinity for maximizing the charging-discharging performance. The crystalline PPy/PAV layer on the TiC nanocube offers unprecedented high capacity (>350 F g-1-PPy at 300 mV s-1 with ΔV = 1.6 V) and cycling stability in a temperature range from -18 °C to 60 °C. The presented hybrid-filler and interfacial crystallization strategies can be applied to the exploration of new-generation high-power conducting polymer-based supercapacitor materials.

  9. Mitochondrial gene polymorphisms alter hepatic cellular energy metabolism and aggravate diet-induced non-alcoholic steatohepatitis

    Torsten Schröder

    2016-04-01

    Full Text Available Objective: Non-alcoholic fatty liver disease (NAFLD is the most common chronic liver disease and is associated with an enhanced risk for liver and cardiovascular diseases and mortality. NAFLD can progress from simple hepatic steatosis to non-alcoholic steatohepatitis (NASH. However, the mechanisms predisposing to this progression remain undefined. Notably, hepatic mitochondrial dysfunction is a common finding in patients with NASH. Due to a lack of appropriate experimental animal models, it has not been evaluated whether this mitochondrial dysfunction plays a causative role for the development of NASH. Methods: To determine the effect of a well-defined mitochondrial dysfunction on liver physiology at baseline and during dietary challenge, C57BL/6J-mtFVB/N mice were employed. This conplastic inbred strain has been previously reported to exhibit decreased mitochondrial respiration likely linked to a non-synonymous gene variation (nt7778 G/T of the mitochondrial ATP synthase protein 8 (mt-ATP8. Results: At baseline conditions, C57BL/6J-mtFVB/N mice displayed hepatic mitochondrial dysfunction characterized by decreased ATP production and increased formation of reactive oxygen species (ROS. Moreover, genes affecting lipid metabolism were differentially expressed, hepatic triglyceride and cholesterol levels were changed in these animals, and various acyl-carnitines were altered, pointing towards an impaired mitochondrial carnitine shuttle. However, over a period of twelve months, no spontaneous hepatic steatosis or inflammation was observed. On the other hand, upon dietary challenge with either a methionine and choline deficient diet or a western-style diet, C57BL/6J-mtFVB/N mice developed aggravated steatohepatitis as characterized by lipid accumulation, ballooning of hepatocytes and infiltration of immune cells. Conclusions: We observed distinct metabolic alterations in mice with a mitochondrial polymorphism associated hepatic mitochondrial

  10. IR-UV double resonance spectroscopic investigation of phenylacetylene-alcohol complexes. Alkyl group induced hydrogen bond switching.

    Singh, Prashant Chandra; Patwari, G Naresh

    2008-06-12

    The electronic transitions of phenylacetylene complexes with water and trifluoroethanol are shifted to the blue, while the corresponding transitions for methanol and ethanol complexes are shifted to the red relative to the phenylacetylene monomer. Fluorescence dip infrared (FDIR) spectra in the O-H stretching region indicate that, in all the cases, phenylacetylene is acting as a hydrogen bond acceptor to the alcohols. The FDIR spectrum in the acetylenic C-H stretching region shows Fermi resonance bands for the bare phenylacetylene, which act as a sensitive tool to probe the intermolecular structures. The FDIR spectra reveal that water and trifluoroethanol interact with the pi electron density of the acetylene C-C triple bond, while methanol and ethanol interact with the pi electron density of the benzene ring. It can be inferred that the hydrogen bonding acceptor site on phenylacetylene switches from the acetylene pi to the benzene pi with lowering in the partial charge on the hydrogen atom of the OH group. The most significant finding is that the intermolecular structures of water and methanol complexes are notably distinct, which, to the best of our knowledge, this is first such observation in the case of complexes of substituted benzenes.

  11. SELECTIVE VULNERABILITY OF EMBRYONIC CELL POPULATIONS TO ETHANOL-INDUCED APOPTOSIS: IMPLICATIONS FOR ALCOHOL RELATED BIRTH DEFECTS AND NEURODEVELOPMENTAL DISORDER

    The locations of cell death and resulting malformations in embryos following teratogen exposure vary depending on the teratogen used, the genotype of the conceptus, and the developmental stage of the embryo at time of exposure. To date, ethanol-induced cell death has been charac...

  12. Effect of alcoholic extract of Entada pursaetha DC on monosodium iodoacetate-induced osteoarthritis pain in rats

    Rashmi R Kumari

    2015-01-01

    Interpretation & conclusions: The present findings showed that the EPE was not only able to mitigate pain and hyperalgesia but also inhibited MIA-induced cartilage degeneration in vivo. EPE may have the potential to become therapeutic modality in the treatment of osteoarthritis. However, further studies need to be done to confirm these findings in other models and clinical trials.

  13. Fish oil alleviated high-fat diet-induced non-alcoholic fatty liver disease via regulating hepatic lipids metabolism and metaflammation: a transcriptomic study.

    Yuan, Fahu; Wang, Hualin; Tian, Yu; Li, Qi; He, Lei; Li, Na; Liu, Zhiguo

    2016-02-01

    Intake of fish oil rich in n-3 polyunsaturated fatty acids (PUFAs) is believed to be beneficial against development of non-alcoholic fatty liver disease (NAFLD). However, the underlying mechanisms remain unclear. This study was to gain further understanding of the potential mechanisms of the protective effects of fish oil against NAFLD. Ten male Sprague-Dawley rats were fed a control diet (CON), a Western style high-fat and high-cholesterol diet (WD), or a WD diet containing fish oil (FOH) for 16 weeks respectively. The development of liver steatosis and fibrosis were verified by histological and biochemical examination. Hepatic transcriptome were extracted for RNA-seq analysis, and particular results were confirmed by real-time polymerase chain reaction (PCR). The consumption of fish oil significantly ameliorated WD-induced dyslipidemia, transaminase elevation, hepatic steatosis, inflammatory infiltration, and fibrosis. Hepatic RNA-Seq analysis showed that long-term intake of fish oil restored the expression of circadian clock-related genes per2 and per3, which were reduced in WD fed animals. Fish oil consumption also corrected the expression levels of genes involved in fatty acid and cholesterol metabolism, such as Srebf1, Fasn, Scd1, Insig2, Cd36, Cyp7a1, Abcg5, Abcg8 and Pcsk9. Moreover, the expression levels of pro-inflammation genes Mcp1, Socs2, Sema4a, and Cd44 in the FOH group were lower than that of WD group, implying that fish oil protects the liver against WD-induced hepatic inflammation. The present study demonstrates fish oil protects against WD-induced NALFD via improving lipid metabolism and ameliorating hepatic inflammation. Our findings add to the current understanding on the benefits of n-3 PUFAs against NAFLD.

  14. Isopropanol alcohol poisoning

    Rubbing alcohol poisoning; Isopropyl alcohol poisoning ... Isopropyl alcohol can be harmful if it is swallowed or gets in the eyes. ... These products contain isopropanol: Alcohol swabs Cleaning supplies ... Rubbing alcohol Other products may also contain isopropanol.

  15. Alcohol Energy Drinks

    ... Home / About Addiction / Alcohol / Alcohol Energy Drinks Alcohol Energy Drinks Read 33960 times font size decrease font size increase font size Print Email Alcohol energy drinks (AEDs) or Caffeinated alcoholic beverages (CABs) are ...

  16. Alcohol and pregnancy

    Drinking alcohol during pregnancy; Fetal alcohol syndrome - pregnancy; FAS - fetal alcohol syndrome ... lead to lifelong damage. DANGERS OF ALCOHOL DURING PREGNANCY Drinking a lot of alcohol during pregnancy can ...

  17. NIAAA Alcohol Treatment Navigator

    ... What to Know About Alcohol Treatment What Is Alcohol Use Disorder (AUD)? What Types of Alcohol Treatment Are Available? ... What to Know About Alcohol Treatment What is alcohol use disorder (AUD)? A health condition that can improve with ...

  18. Silibinin Restores NAD⁺ Levels and Induces the SIRT1/AMPK Pathway in Non-Alcoholic Fatty Liver.

    Salomone, Federico; Barbagallo, Ignazio; Godos, Justyna; Lembo, Vincenzo; Currenti, Walter; Cinà, Diana; Avola, Roberto; D'Orazio, Nicolantonio; Morisco, Filomena; Galvano, Fabio; Li Volti, Giovanni

    2017-09-30

    Nicotinamide adenine dinucleotide (NAD⁺) homeostasis is emerging as a key player in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) and is tightly linked to the SIRT1/5'-AMP-activated protein kinase (AMPK) pathway. Silibinin, the main component of silymarin, has been proposed as a nutraceutical for the treatment of NAFLD. In this study, we aimed to identify whether silibinin may influence the NAD⁺/SIRT1 axis. To this end, C57BL/6 mice were fed a high fat diet (HFD) for 16 weeks, and were treated with silibinin or vehicle during the last 8 weeks. HepG2 cells were treated with 0.25 mM palmitate for 24 h with silibinin 25 µM or vehicle. HFD and palmitate administration led to oxidative stress, poly-(ADP-ribose)-polymerase (PARP) activation, NAD⁺ consumption, and lower SIRT1 activity. In mice fed the HFD, and in HepG2 treated with palmitate, we consistently observed lower levels of phospho-AMPK Thr172 and phospho-acetyl-CoA carboxylase Ser79 and higher levels of nuclear sterol regulatory element-binding protein 1 activity, indicating de novo lipogenesis. Treatment of mice and HepG2 with silibinin abolished oxidative stress, and inhibited PARP activation thus restoring the NAD⁺ pool. In agreement with preserved NAD⁺ levels, SIRT1 activity and AMPK phosphorylation returned to control levels in mice and HepG2. Our results further indicate silibinin as a promising molecule for the treatment of NAFLD.

  19. Lack of ClC-2 Alleviates High Fat Diet-Induced Insulin Resistance and Non-Alcoholic Fatty Liver Disease

    Dongxia Fu

    2018-03-01

    Full Text Available Background/Aims: Non-alcoholic fatty liver disease (NAFLD is the most common cause of chronic liver disease. This study aims to investigate whether chloride channel 2 (ClC-2 is involved in high fat diet (HFD-induced NAFLD and possible molecular mechanisms. Methods: ClC-2 expression was liver-specifically downregulated using adeno-associated virus in C57BL/6 mice treated with a chow diet or HFD for 12 weeks. Peripheral blood and liver tissues were collected for biochemical and pathological estimation respectively. Western blotting was applied to detect the protein expressions of lipid synthesis-related enzymes and the phosphorylated level of IRS-1, Akt and mTOR. Results: ClC-2 mRNA level was significantly increased in patients with non-alcoholic steatohepatitis, which positively correlated with the plasma levels of alanine transaminase (ALT, aspartate transaminase (AST and insulin. Knockdown of ClC-2 in liver attenuated HFD-induced weight gain, obesity, hepatocellular ballooning, and liver lipid accumulation and fibrosis, accompanied by reduced plasma free fatty acid (FFA, triglyceride (TG, total cholesterol (TC, ALT, AST, glucose and insulin levels and homeostasis model of insulin resistance (HOMA-IR value. Moreover, HFD-treated mice lacking ClC-2 showed inhibited hepatic lipid accumulation via regulating lipid metabolism through decreasing sterol regulatory element binding protein (SREBP-1c expression and its downstream targeting enzymes such as fatty acid synthase (FAS, HMG-CoA reductase (HMGCR and acetyl-Coenzyme A carboxylase (ACCα. In addition, in vivo and in vitro results demonstrated that ClC-2 downregulation in HFD-treated mice or HepG2 cells increased the sensitivity to insulin via activation of IRS-1/Akt/mTOR signaling pathway. Conclusion: Our present study reveals a critical role of ClC-2 in regulating metabolic diseases. Mice lacking ClC-2 are associated with a remarkably beneficial metabolic phenotype, suggesting that decreasing Cl

  20. Alcoholic epilepsy. A definition and a description of other convulsions related to alcoholism.

    Yamane, H; Katoh, N

    1981-01-01

    The role of alcohol intake and withdrawal in so-called alcoholic epilepsy is discussed and illustrated by case reports. A classification is made which includes definitions of withdrawal convulsions, tetany-like withdrawal convulsions and alcohol-induced epileptic fits, with or without predisposing features.

  1. Ameliorative Effect of Hydroethanolic Leaf Extract of Byrsocarpus coccineus in Alcohol- and Sucrose-Induced Hypertension in Rats

    Abidemi J. Akindele

    2014-07-01

    Full Text Available Hypertension remains a major health problem worldwide considering the prevalence of morbidity and mortality. Plants remain a reliable source of efficacious and better tolerated drugs and botanicals. This study was designed to investigate the effect of the chemo-profiled hydroethanolic leaf extract of Byrsocarpus coccineus in ethanol- and sucrose-induced hypertension. Groups of rats were treated orally (p.o. with distilled water (10 ml/kg, ethanol (35%; 3 g/kg, sucrose (5-7%, and B. coccineus (100, 200, and 400 mg/kg, and nifedipine together with ethanol and sucrose separately for 8 weeks. At the end of the treatment period, blood pressure and heart rate of rats were determined. Blood was collected for serum biochemical parameters and lipid profile assessment, and the liver, aorta, kidney, and heart were harvested for estimation of in vivo antioxidants and malondialdehyde (MDA. Results obtained in this study showed that B. coccineus at the various doses administered reduced the systolic, diastolic, and arterial blood pressure elevated by ethanol and sucrose. Also, the extract reversed the reduction in catalase (CAT, reduced glutathione (GSH, glutathione peroxidase (GPx, and superoxide dismutase (SOD induced by ethanol and sucrose. The level of MDA was reduced compared to the ethanol- and sucrose-induced hypertensive group. With respect to lipid profile, administration of B. coccineus at the various doses reduced the levels of triglycerides, low-density lipoprotein (LDL, cholesterol, and atherogenic indices, compared to the ethanol and sucrose groups. In conclusion the hydroethanolic leaf extract of B. coccineus exerted significant antihypertensive effect and this is probably related to the antioxidant property and improvement of lipid profile observed in this study.

  2. Alcoholism and alcohol drinking habits predicted from alcohol dehydrogenase genes

    Tolstrup, J.S.; Nordestgaard, Børge; Rasmussen, S.

    2008-01-01

    Alcohol is degraded primarily by alcohol dehydrogenase (ADH) wherein genetic variation that affects the rate of alcohol degradation is found in ADH1B and ADH1C. It is biologically plausible that these variations may be associated with alcohol drinking habits and alcoholism. By genotyping 9080 whi...

  3. Alcohol Intolerance

    ... ingredients commonly found in alcoholic beverages, especially in beer or wine, can cause intolerance reactions. These include: Sulfites or other preservatives Chemicals, grains or other ingredients Histamine, a byproduct of fermentation or brewing In some cases, reactions can be ...

  4. Alcohol Poisoning

    ... than eight breaths a minute) Irregular breathing (a gap of more than 10 seconds between breaths) Blue- ... about alcohol by their parents and who report close relationships with their parents are less likely to ...

  5. Alcoholic neuropathy

    ... Frequently inspecting the feet and shoes to reduce injury caused by pressure or objects in the shoes Guarding the extremities to prevent injury from pressure Alcohol must be stopped to prevent ...

  6. Potential nephrotoxic effects produced by steroidal saponins from hydro alcoholic extract of Tribulus terrestris in STZ-induced diabetic rats.

    Gandhi, Sonia; Srinivasan, B P; Akarte, Atul S

    2013-09-01

    Chronic hyperglycemia leads to the development of microvascular complications like diabetic nephropathy. The present study investigated the potential effects of the hydroalcoholic extract of Tribulus terrestris, a plant of Zygophyllaceae family, on the renal complications in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by administering STZ (90 mg/kg) to the 2-days old neonates. After 6 weeks of induction, diabetic rats were treated with 50 mg/kg hydroalcoholic extract of T. terrestris for 8 weeks. The anti-hyperglycaemic nature was confirmed by reduction in blood glucose and improvement in insulin levels. Diabetic renal injury associated with decrease in total proteins and albumin levels was observed to be improved by T. terrestris extract. Glomerular filtration rate along with inflammatory and growth factors, adiponectin and erythropoietin were also improved by the treatment, though the findings were not significant. However, the beneficial antidiabetic effects of T. terrestris extract in plasma were not observed in kidney histopathology. This was confirmed by the quantitative estimation of unhydrolyzed fraction of saponins (major component: protodioscin) in plasma and kidney samples of normal and diabetic rats. Hence, it can be concluded that 8 weeks treatment with T. terrestris extract produces potential toxic effects in kidney, which are independent of its anti-diabetic action.

  7. Chronic Alcohol Ingestion Worsens Survival and Alters Gut Epithelial Apoptosis and Cd8+ T Cell Function after Pseudomonas Aeruginosa Pneumonia-Induced Sepsis.

    Klingensmith, Nathan J; Fay, Katherine T; Lyons, John D; Chen, Ching-Wen; Otani, Shunsuke; Liang, Zhe; Chihade, Deena B; Burd, Eileen M; Ford, Mandy L; Coopersmith, Craig M

    2018-04-16

    Mortality is higher in septic patients with a history of alcohol use disorder than in septic patients without a history of chronic alcohol usage. We have previously described a model of chronic alcohol ingestion followed by sepsis from cecal ligation and puncture in which alcohol-fed septic mice have higher mortality than water-fed septic mice, associated with altered gut integrity and increased production of TNF and IFNγ by splenic CD4 T cells without alterations in CD8 T cell function. The purpose of this study was to determine whether this represents a common host response to the combination of alcohol and sepsis by creating a new model in which mice with chronic alcohol ingestion were subjected to a different model of sepsis. C57Bl/6 mice were randomized to receive either alcohol or water for 12 weeks and then subjected to Pseudomonas aeruginosa pneumonia. Mice were sacrificed either 24 hours after the onset of sepsis or followed for survival. Alcohol-fed septic mice had significantly higher 7-day mortality than water-fed septic mice (96% vs 58%). This was associated with a 5-fold increase in intestinal apoptosis in alcohol-fed septic animals, accompanied by an increase in the pro-apoptotic protein Bax. Serum IL-6 levels were higher and IL-2 levels were lower in alcohol-fed septic mice. In contrast, CD8 T cell frequency was lower in alcohol-fed mice than water-fed septic mice, associated with increased production of IFNγ and TNF in stimulated splenocytes. No significant differences were noted in CD4 T cells, lung injury or bacteremia. Mice with chronic alcohol ingestion thus have increased mortality regardless of their septic insult, associated with changes in both the gut and the immune system.

  8. Alcohol abuse and related disorders treatment of alcohol dependence

    Yu. P. Sivolap

    2014-01-01

    Full Text Available Alcohol abuse and alcoholism are the leading causes of worse health and increased mortality rates. Excessive alcohol consumption is the third leading cause of the global burden of diseases and a leading factor for lower lifespan and higher mortality. Alcohol abuse decreases working capacity and efficiency and requires the increased cost of the treatment of alcohol-induced disorders, which entails serious economic losses. The unfavorable medical and social consequences of excessive alcohol use determine the importance of effective treatment for alcoholism. The goals of rational pharmacotherapy of alcohol dependence are to enhance GABA neurotransmission, to suppress glutamate neurotransmission, to act on serotonin neurotransmission, to correct water-electrolyte balance, and to compensate for thiamine deficiency. Alcoholism treatment consists of two steps: 1 the prevention and treatment of alcohol withdrawal syndrome and its complications (withdrawal convulsions and delirium alcoholicum; 2 antirecurrent (maintenance therapy. Benzodiazepines are the drugs of choice in alleviating alcohol withdrawal and preventing its convulsive attacks and delirium alcoholicum. Diazepam and chlordiazepoxide are most commonly used for this purpose; the safer drugs oxazepam and lorazepam are given to the elderly and patients with severe liver lesions. Anticonvulsants having normothymic properties, such as carbamazepine, valproic acid, topiramate, and lamotrigine, are a definite alternative to benzodiazepines. The traditional Russian clinical practice (clearance detoxification has not a scientific base or significant impact on alcohol withdrawal-related states in addicts. Relapse prevention and maintenance therapy for alcohol dependence are performed using disulfiram, acamprosate, and naltrexone; since 2013 the European Union member countries have been using, besides these agents, nalmefene that is being registered in Russia. Memantine and a number of other

  9. The economic impact of alcohol abuse and alcoholism.

    Burke, T R

    1988-01-01

    The economic effects of alcohol abuse are as damaging to the nation as the health effects, affecting the family, the community, and persons of all ages. Underaged drinking is interfering with children's development, affecting the nation's ability to respond to economic challenge in the future. The college aged may be the most difficult to educate about alcohol abuse because of drinking patterns established at an early age and susceptibility to advertising inducements. Health care costs for families with an alcoholic member are twice those for families without one, and up to half of all emergency room admissions are alcohol related. Fetal alcohol syndrome is one of the top three known causes of birth defects, and is totally preventable. Alcohol abuse and alcoholism are estimated to have cost the nation $117 billion in 1983, while nonalcoholic drug abuse that year cost $60 billion. Costs of alcohol abuse are expected to be $136 billion a year by 1990, mostly from lost productivity and employment. Between 6 and 7 million workers are alcoholic, with an undetermined loss of productivity, profits, and competitiveness of American business. Alcohol abuse contributes to the high health care costs of the elderly beneficiaries of Federal health financing programs. Heavily affected minorities include blacks, Hispanics, and Native Americans. Society tends to treat the medical and social consequences of alcohol abuse, rather than its causes. Although our experience with the consequences of alcohol abuse is greater than that for any other drug, public concern for its prevention and treatment is less than for other major illnesses or abuse of other drugs. Alcohol abuse is a problem being given high priority within the Department in an effort to create a national agenda on the issue and to try to impart a greater sense of urgency about the problems. Ways are being explored to integrate alcoholism activities into more Departmental programs. Employee assistance programs for alcohol

  10. Chronic alcoholism in rats induces a compensatory response, preserving brain thiamine diphosphate, but the brain 2-oxo acid dehydrogenases are inactivated despite unchanged coenzyme levels.

    Parkhomenko, Yulia M; Kudryavtsev, Pavel A; Pylypchuk, Svetlana Yu; Chekhivska, Lilia I; Stepanenko, Svetlana P; Sergiichuk, Andrej A; Bunik, Victoria I

    2011-06-01

    Thiamine-dependent changes in alcoholic brain were studied using a rat model. Brain thiamine and its mono- and diphosphates were not reduced after 20 weeks of alcohol exposure. However, alcoholism increased both synaptosomal thiamine uptake and thiamine diphosphate synthesis in brain, pointing to mechanisms preserving thiamine diphosphate in the alcoholic brain. In spite of the unchanged level of the coenzyme thiamine diphosphate, activities of the mitochondrial 2-oxoglutarate and pyruvate dehydrogenase complexes decreased in alcoholic brain. The inactivation of pyruvate dehydrogenase complex was caused by its increased phosphorylation. The inactivation of 2-oxoglutarate dehydrogenase complex (OGDHC) correlated with a decrease in free thiols resulting from an elevation of reactive oxygen species. Abstinence from alcohol following exposure to alcohol reactivated OGDHC along with restoration of the free thiol content. However, restoration of enzyme activity occurred before normalization of reactive oxygen species levels. Hence, the redox status of cellular thiols mediates the action of oxidative stress on OGDHC in alcoholic brain. As a result, upon chronic alcohol consumption, physiological mechanisms to counteract the thiamine deficiency and silence pyruvate dehydrogenase are activated in rat brain, whereas OGDHC is inactivated due to impaired antioxidant ability. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

  11. Effects of hydro-alcoholic extract of Vitex agnus-castus fruit on kidney of D-galactose-induced aging model in female mice.

    Oroojan, A A; Ahangarpour, A; Khorsandi, L; Najimi, S A

    2016-01-01

    The aim of the present study was to evaluate the effect of a hydro-alcoholic extract of Vitex agnus-castus (VAC) fruit on blood urea nitrogen (BUN), creatinine (Cr) and, kidney histology of a female mouse model of D-galactose induced aging. In this experimental study, 72 NMRI mice were divided into 6 groups: control, VAC, D-galactose, D-galactose+VAC, aging, and aging+VAC. D-galactose was injected for 45 days and, VAC extract administered in the last 7 days, twice a day. Serum BUN and Cr levels were not significantly changed in the D-galactose and natural aged animals in comparison to control group. Histological changes such as nuclear pyknosis, proximal cell swelling, infiltration of inflammatory cells, tubular dilatation and, vasodilatation were observed in both D-galactose and natural aged mice. Further, glomerules diameter was decreased in them. Administration of VAC could attenuate the histological alterations. These results indicate that VAC may have beneficial effects on aging and aging related kidney disease.

  12. Ethanol-induced oxidative stress and acetaldehyde formation in rat mammary tissue: Potential factors involved in alcohol drinking promotion of breast cancer

    Castro, Gerardo D.; Rodriguez de Castro, Carmen; Maciel, Maria E.; Fanelli, Silvia L.; Cignoli de Ferreyra, Elida; Gomez, Maria I. Diaz; Castro, Jose A.

    2006-01-01

    Recent studies from our laboratory provided evidence that part of the carcinogenic effects of ethanol consumption might be related to its in situ metabolism at cytosolic and microsomal levels, to the mutagen acetaldehyde and to hydroxyl and 1-hydroxyethyl radicals. In this work, we report on our experiments where Sprague-Dawley female rats were exposed to the standard Lieber and De Carli diet for 28 days. We observed: the induction of the (xanthineoxidoreductase mediated) cytosolic and microsomal (lipoxygenase mediated) pathways of ethanol metabolism; promotion of oxidative stress as shown by increased formation of lipid hydroperoxides; delay in the t-butylhydroperoxide induced chemiluminiscence, and a significant decrease in protein sulfhydryls. In addition, the epithelial cells showed ultrastructural alterations consisting of markedly irregular nuclei, with frequent invaginations at the level of the nuclear envelope, condensation of chromatin around the inner nuclear membrane, and marked dilatation of the nuclear pores showing filamentous material exiting to the cytoplasm. In conclusion, the presence in mammary epithelial cells of cytosolic and microsomal pathways of ethanol bioactivation to carcinogenic and to tumorigenic metabolites might play a role in alcohol promotion of breast cancer

  13. Protective effects of orange (Citrus sinensis L.) peel aqueous extract and hesperidin on oxidative stress and peptic ulcer induced by alcohol in rat.

    Selmi, Slimen; Rtibi, Kais; Grami, Dhekra; Sebai, Hichem; Marzouki, Lamjed

    2017-08-14

    Massive alcohol drinking can lead to gastric ulcer. In the present study we investigated the gastroprotective effect of Citrus sinensis peel aqueous extract (CSPE) and Hesperidin (H) in ethanol (EtOH) induced oxidative stress and peptic ulcer in rats. Seventy adult male Wistar rats were divided into seven groups of 10 each: control, EtOH (4 g/kg b.w.), EtOH + various doses of CSPE (100, 200 and 400 mg/kg, b.w.), EtOH + Hesperidin (50 mg/kg, p.o.) and EtOH + Omeprazole (OM, 20 mg/kg, p.o.). Animals were perorally (p.o.) pre-treated with CSPE during 15 days and intoxicated with a single oral administration of EtOH (4 g/kg b.w.) during 2 h. Gastric ulcer was induced in rats with a single dose of ethanol (EtOH). Ulcer index, gene expression of gastric cyclooxygenase-2 (COX-2), tumor necrosis factor alpha (TNF-α), malondialdhyde (MDA), hydrogen peroxide H 2 O 2 and Thiol groups (-SH) content in stomach and antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and gluthation peroxidise (GPx) were measured. Furthermore, histopathological examinations were performed. The results showed that ethanol induced gastric damage, improving oxidative stress markers level such as MDA (121 ± 4.45 nmol/mg proteins) and H 2 O 2 (24.62 ± 1.04 μmol/mg proteins), increased pro-inflammatory cytokine (TNF-α level), as well as the expression of COX-2 in the ethanol group. However, a significant depletion of enzymatic and non-enzymatic antioxidants were observed, such as, GPx (72%), SOD (57.5%), CAT (41.6%) and -SH (50%). The lesions were associated with severe histopathological damage. The both Citrus sinensis peel aqueous extract (CSPE) and hesperidin significantly protect against all gastric damages caused by ethanol administration in rats. We propose that CSPE and hesperidin exhibit protective effects in EtOH-induced peptic ulcer in rat. This protection might be related in to part its antioxidant properties as well as its opposite effects on some studied

  14. Study of ethanol-induced Golgi disorganization reveals the potential mechanism of alcohol-impaired N-glycosylation

    Casey, Carol A.; Bhat, Ganapati; Holzapfel, Melissa S.; Petrosyan, Armen

    2016-01-01

    Background It is known that ethanol (EtOH) and its metabolites have a negative effect on protein glycosylation. The fragmentation of the Golgi apparatus induced by alteration of the structure of largest Golgi matrix protein, giantin, is the major consequence of damaging effects of EtOH-metabolism on the Golgi, however, the link between this and abnormal glycosylation remains unknown. Because previously we have shown that Golgi morphology dictates glycosylation, we examined the effect EtOH administration has on function of Golgi residential enzymes involved in N-glycosylation. Methods HepG2 cells transfected with mouse ADH1 (VA-13 cells) were treated with 35 mM ethanol for 72 h. Male Wistar rats were pair-fed Lieber-DeCarli diets for 5 to 8 weeks. Characterization of Golgi-associated mannosyl (α-1,3-)-glycoprotein beta-1,2-N-acetylglucosaminyltransferase (MGAT1), α-1,2-mannosidase (Man-I) and α-mannosidase II (Man-II) were performed in VA-13 cells and rat hepatocytes followed by 3D Structured Illumination Microscopy (SIM). Results First, we detected that EtOH administration results in the loss of sialylated N-glycans on asialoglycoprotein receptor, however the high mannose-type N-glycans are increased. Further analysis by 3D SIM microscopy revealed that EtOH treatment despite Golgi disorganization does not change cis-Golgi localization for Man-I, but does induce medial-to-cis relocation of MGAT1 and Man-II. Using different approaches, including electron microscopy, we revealed that EtOH treatment results in dysfunction of Arf1 GTPase followed by a deficiency in COPI vesicles at the Golgi. Silencing beta-COP or expression of GDP-bound mutant Arf1(T31N) mimics the EtOH effect on retaining MGAT1 and Man-II at the cis-Golgi, suggesting that (a) EtOH specifically blocks activation of Arf1, and (b) EtOH alters the proper localization of Golgi enzymes through impairment of COPI. Importantly, the level of MGAT1 was reduced, because likely MGAT1, contrary to Man-I and Man

  15. Effect of Citrullus colocynthis hydro-alcoholic extract on hormonal and folliculogenesis process in estradiol valerate-induced PCOs rats model: An experimental study

    Mohammad Hossein Barzegar

    2017-12-01

    Full Text Available Background: Citrullus colocynthis (CCT is used as the anti-diabetic and antioxidant agent. Polycystic ovarian syndrome (PCOS is a reproductive disorder which level of gonadotropins and sexual hormones are imbalanced. Objective: We evaluated the effect of CCT hydro-alcoholic extract on hormonal and folliculogenesis process in estradiol valerate-induced PCOs rats’ model. Materials and Methods: 40 female adult Wistar rats divided into five groups (n=8each: Group I (control only injected by sesame oil as estradiol valerate solvent, group II (Sham was orally received normal saline after estradiol valerate- induced polycystic ovarian syndrome (4 mg/rat estradiol valerate, intramuscularly, and three experimental groups, that after induction of PCOS within 60 days, received orally 50 mg/kg CCT extract (group III, 50mg/kg metformin (group IV, and CCT extract+ metformin (group V for 20 days. The serum concentration level of luteinizing, testosterone and follicle stimulating hormones were measured using ELISA method and the serum concentration level of glucose were measured using the oxidative method (glucose meter. Histological study of ovary tissue carried out by hematoxylin-eosin staining. Results: There was a significant reduction in luteinizing hormone and testosterone in III-V groups compared to Sham group, whereas follicle stimulating hormone in III-V groups was not significantly changed in comparison with Sham group. Histological investigations showed a significant increase in number of preantral and antral follicles and corpus luteum in the experimental groups compared to group II. Conclusion: Marked improvement in hormonal and histological symptoms of PCOS may be due to CCT effects hence, CCT can potentially be considered as an effective drug for treatment of PCOS

  16. Spleen-derived interleukin-10 downregulates the severity of high-fat diet-induced non-alcoholic fatty pancreas disease.

    Koro Gotoh

    Full Text Available Obesity is associated with systemic low-grade inflammation and is a risk factor for non-alcoholic fatty pancreas disease (NAFPD, but the molecular mechanisms of these associations are not clear. Interleukin (IL-10, a potent anti-inflammatory cytokine, is released during acute pancreatitis and is known to limit inflammatory responses by downregulating the release of proinflammatory mediators. The origin of IL-10 that suppresses pancreatitis has not been investigated. Since obesity is known to reduce expression of proinflammatory cytokines in the spleen, we examined whether spleen-derived IL-10 regulates NAFPD caused by high-fat (HF diet-induced obesity. The following investigations were performed: 1 IL-10 induction from spleen was examined in male mice fed a HF diet; 2 triglyceride content, expression of pro- and anti-inflammatory cytokines and infiltration of M1 and M2 macrophages were determined to evaluate ectopic fat accumulation and inflammatory responses in the pancreas of splenectomy (SPX-treated mice fed HF diet; 3 exogenous IL-10 was systemically administered to SPX-treated obese mice and the resulting pathogenesis caused by SPX was assessed; and 4 IL-10 knockout (IL-10KO mice were treated with SPX and ectopic fat deposition and inflammatory conditions in the pancreas were investigated. Obesity impaired the ability of the spleen to synthesize cytokines, including IL-10. SPX aggravated fat accumulation and inflammatory responses in the pancreas of HF diet-induced obese mice and these effects were inhibited by systemic administration of IL-10. Moreover, SPX had little effect on fat deposition and inflammatory responses in the pancreas of IL-10KO mice. Our findings indicate that obesity reduces IL-10 production by the spleen and that spleen-derived IL-10 may protect against the development of NAFPD.

  17. Effect of Citrullus colocynthis hydro-alcoholic extract on hormonal and folliculogenesis process in estradiol valerate-induced PCOs rats model: An experimental study.

    Barzegar, Mohammad Hossein; Khazali, Homayoun; Kalantar, Seyyed Mehdi; Khoradmehr, Arezoo

    2017-10-01

    Citrullus colocynthis (CCT) is used as the anti-diabetic and antioxidant agent. Polycystic ovarian syndrome (PCOS) is a reproductive disorder which level of gonadotropins and sexual hormones are imbalanced. We evaluated the effect of CCT hydro-alcoholic extract on hormonal and folliculogenesis process in estradiol valerate-induced PCOs rats' model. 40 female adult Wistar rats divided into five groups (n=8each: Group I (control) only injected by sesame oil as estradiol valerate solvent, group II (Sham) was orally received normal saline after estradiol valerate- induced polycystic ovarian syndrome (4 mg/rat estradiol valerate, intramuscularly), and three experimental groups, that after induction of PCOS within 60 days, received orally 50 mg/kg CCT extract (group III), 50mg/kg metformin (group IV), and CCT extract+ metformin (group V) for 20 days. The serum concentration level of luteinizing, testosterone and follicle stimulating hormones were measured using ELISA method and the serum concentration level of glucose were measured using the oxidative method (glucose meter). Histological study of ovary tissue carried out by hematoxylin-eosin staining. There was a significant reduction in luteinizing hormone and testosterone in III-V groups compared to Sham group, whereas follicle stimulating hormone in III-V groups was not significantly changed in comparison with Sham group. Histological investigations showed a significant increase in number of preantral and antral follicles and corpus luteum in the experimental groups compared to group II. Marked improvement in hormonal and histological symptoms of PCOS may be due to CCT effects hence, CCT can potentially be considered as an effective drug for treatment of PCOS.

  18. Alcohol Alert: Genetics of Alcoholism

    ... daily rhythm for various functions (e.g., body temperature or blood pressure) that is controlled by certain “ ... A special section delves more deeply into specific classes of genes and their relationship to alcoholism. The ...

  19. Alcohol consumption promotes diethylnitrosamine-induced hepatocarcinogenesis in male mice through the activation of the Wnt/Beta-catenin signaling pathway

    Although alcohol effects within the liver have been extensively studied, the complex mechanisms by which alcohol causes liver cancer are not well understood. It has been suggested that ethanol (EtOH) metabolism promotes tumor growth by increasing hepatocyte proliferation. In this study, we develop...

  20. Effect of Hydro-Alcoholic Extract of Teucrium Polium on Castor Oil-Induced Diarrhea in Male Rat

    Mohammad Allahtavakoli

    2013-06-01

    Full Text Available Background: Diarrhea is one of the world's health problems as the most common causes of death in children. In this study, the effect of Teucrium Polium (TP extract on diarrhea induced by castor oil has been studied. Materials and Methods: 30 male rats were divided into five equal groups containing extract with doses of 100, 200 and 600 mg/kg; diphenoxylate (5 mg/kg; and control group or vehicle (normal saline groups. One hour after feeding the drugs or vehicle in the volume of 10 ml/kg, 2 ml of castor oil were fed to each animal through an oral-gastric catheter. Then excrements of animals were separately observed in the cages for 4 hours and their quality, frequency and stool weight were determined. Data analysis was performed using one-way ANOVA and Tukey post-test and p<0.05 was considered as significant.Results: Diphenoxylate and 600 mg/kg dose of TP reduced the percentage of the weight loss of animals, their excretion frequency and defecation index (p< 0.001. The 600 mg/kg dose of TP decreased the fecal water content compared to the control group (p< 0.01.Conclusion: Based on our data, essential oil of TP has an effect similar to diphenoxylate on the reduction of osmotic diarrhea symptoms and also reduces the volume of excreted water

  1. Stereological study of the effect of ginger's alcoholic extract on the testis in busulfan-induced infertility in rats

    Hossein Bordbar

    2013-06-01

    Full Text Available Background: In traditional medicine zingiber officinale used to regulate female menstural cycle and treat male infertility. Recent studies have suggested the possible role of ginger extract in improving the testicular damage of busulfan. Objective: The aim of this study was to evaluate the effects of zingiber officinale on the sperm parameters, testosterone level and the volume of the testes and seminiferous tubules by stereological methods. Materials and Methods: Fifty rats were divided into four groups. All the rats were given a single intraperitoneally injection of 5mg/kg busulfan solution. The first group was kept as busulfan control, while the other groups were orally administrated ginger extract in graded doses of 50, 100 and 150mg/kg b.wt, for 48 consecutive days. At the end, all animals were anesthetized and their testes and vas deference were removed, fixed, embedded, and stained. The volume of testes and seminiferous tubules were estimated by cavalieri methods. Results: The result showed, that zingiber officinale increased the volumes of seminiferous tubule in 100mg/kg treated group compared to control group. Sperm count (706×105 and 682×105 and the level of testosterone (50.90 ng/mL and 54.10 ng/mL enhanced in 100 mg/kg and 150 mg/kg treated groups compared to control group (p=0.00. Conclusion: It seems that zingiber officinale stimulate male reproductive system in induce busulfan infertility

  2. The effects of cocaine, alcohol and cocaine/alcohol combinations in conditioned taste aversion learning.

    Busse, Gregory D; Verendeev, Andrey; Jones, Jermaine; Riley, Anthony L

    2005-09-01

    We have recently reported that alcohol attenuates cocaine place preferences. Although the basis for this effect is unknown, alcohol may attenuate cocaine reward by potentiating its aversive effects. To examine this possibility, these experiments assessed the effects of alcohol on cocaine-induced taste aversions under conditions similar to those that resulted in attenuated place preferences. Specifically, Experiments 1 and 2 assessed the effects of alcohol (0.5 g/kg) on taste aversions induced by 20, 30 and 40 mg/kg cocaine. Experiment 3 examined the role of intertrial interval in the effects of alcohol (0.5 g/kg) on cocaine (30 mg/kg) taste aversions. In Experiments 1 and 2, cocaine was effective at conditioning aversions. Alcohol produced no measurable effect. Combining cocaine and alcohol produced no greater aversion than cocaine alone (and, in fact, weakened aversions at the lowest dose of cocaine). In Experiment 3, varying the intertrial interval from 3 days (as in the case of Experiments 1 and 2) to 1 day (a procedure identical to that in which alcohol attenuated cocaine place preferences) resulted in significant alcohol- and cocaine-induced taste aversions. Nonetheless, alcohol remained ineffective in potentiating cocaine aversions. Thus, under these conditions alcohol does not potentiate cocaine's aversiveness. These results were discussed in terms of their implication for the effects of alcohol on cocaine-induced place preferences. Further, the effects of alcohol on place preferences conditioned by cocaine were discussed in relation to other assessments of the effects of alcohol on the affective properties of cocaine and the implications of these interactions for alcohol and cocaine co-use.

  3. Alcohol and Apoptosis: Friends or Foes?

    Rodriguez, Ana; Chawla, Karan; Umoh, Nsini A; Cousins, Valerie M; Ketegou, Assama; Reddy, Madhumati G; AlRubaiee, Mustafa; Haddad, Georges E; Burke, Mark W

    2015-11-19

    Alcohol abuse causes 79,000 deaths stemming from severe organ damage in the United States every year. Clinical manifestations of long-term alcohol abuse on the cardiac muscle include defective contractility with the development of dilated cardiomyopathy and low-output heart failure; which has poor prognosis with less than 25% survival for more than three years. In contrast, low alcohol consumption has been associated with reduced risk of cardiovascular disease, however the mechanism of this phenomenon remains elusive. The aim of this study was to determine the significance of apoptosis as a mediating factor in cardiac function following chronic high alcohol versus low alcohol exposure. Adult rats were provided 5 mM (low alcohol), 100 mM (high alcohol) or pair-fed non-alcohol controls for 4-5 months. The hearts were dissected, sectioned and stained with cresyl violet or immunohistochemically for caspase-3, a putative marker for apoptosis. Cardiomyocytes were isolated to determine the effects of alcohol exposure on cell contraction and relaxation. High alcohol animals displayed a marked thinning of the left ventricular wall combined with elevated caspase-3 activity and decreased contractility. In contrast, low alcohol was associated with increased contractility and decreased apoptosis suggesting an overall protective mechanism induced by low levels of alcohol exposure.

  4. Role of pentoxifylline in non-alcoholic fatty liver disease in high-fat diet-induced obesity in mice.

    Acedo, Simone Coghetto; Caria, Cintia Rabelo E Paiva; Gotardo, Érica Martins Ferreira; Pereira, José Aires; Pedrazzoli, José; Ribeiro, Marcelo Lima; Gambero, Alessandra

    2015-10-28

    To study pentoxifylline effects in liver and adipose tissue inflammation in obese mice induced by high-fat diet (HFD). Male swiss mice (6-wk old) were fed a high-fat diet (HFD; 60% kcal from fat) or AIN-93 (control diet; 15% kcal from fat) for 12 wk and received pentoxifylline intraperitoneally (100 mg/kg per day) for the last 14 d. Glucose homeostasis was evaluated by measurements of basal glucose blood levels and insulin tolerance test two days before the end of the protocol. Final body weight was assessed. Epididymal adipose tissue was collected and weighted for adiposity evaluation. Liver and adipose tissue biopsies were homogenized in solubilization buffer and cytokines were measured in supernatant by enzyme immunoassay or multiplex kit, respectively. Hepatic histopathologic analyses were performed in sections of paraformaldehyde-fixed, paraffin-embedded liver specimens stained with hematoxylin-eosin by an independent pathologist. Steatosis (macrovesicular and microvesicular), ballooning degeneration and inflammation were histopathologically determined. Triglycerides measurements were performed after lipid extraction in liver tissue. Pentoxifylline treatment reduced microsteatosis and tumor necrosis factor (TNF)-α in liver (156.3 ± 17.2 and 62.6 ± 7.6 pg/mL of TNF-α for non-treated and treated obese mice, respectively; P < 0.05). Serum aspartate aminotransferase levels were also reduced (23.2 ± 6.9 and 12.1 ± 1.6 U/L for non-treated and treated obese mice, respectively; P < 0.05) but had no effect on glucose homeostasis. In obese adipose tissue, pentoxifylline reduced TNF-α (106.1 ± 17.6 and 51.1 ± 9.6 pg/mL for non-treated and treated obese mice, respectively; P < 0.05) and interleukin-6 (340.8 ± 51.3 and 166.6 ± 22.5 pg/mL for non-treated and treated obese mice, respectively; P < 0.05) levels; however, leptin (8.1 ± 0.7 and 23.1 ± 2.9 ng/mL for non-treated and treated lean mice, respectively; P < 0.05) and plasminogen activator inhibitor-1 (600

  5. Metformin-Induced Changes of the Coding Transcriptome and Non-Coding RNAs in the Livers of Non-Alcoholic Fatty Liver Disease Mice.

    Guo, Jun; Zhou, Yuan; Cheng, Yafen; Fang, Weiwei; Hu, Gang; Wei, Jie; Lin, Yajun; Man, Yong; Guo, Lixin; Sun, Mingxiao; Cui, Qinghua; Li, Jian

    2018-01-01

    Recent studies have suggested that changes in non-coding mRNA play a key role in the progression of non-alcoholic fatty liver disease (NAFLD). Metformin is now recommended and effective for the treatment of NAFLD. We hope the current analyses of the non-coding mRNA transcriptome will provide a better presentation of the potential roles of mRNAs and long non-coding RNAs (lncRNAs) that underlie NAFLD and metformin intervention. The present study mainly analysed changes in the coding transcriptome and non-coding RNAs after the application of a five-week metformin intervention. Liver samples from three groups of mice were harvested for transcriptome profiling, which covered mRNA, lncRNA, microRNA (miRNA) and circular RNA (circRNA), using a microarray technique. A systematic alleviation of high-fat diet (HFD)-induced transcriptome alterations by metformin was observed. The metformin treatment largely reversed the correlations with diabetes-related pathways. Our analysis also suggested interaction networks between differentially expressed lncRNAs and known hepatic disease genes and interactions between circRNA and their disease-related miRNA partners. Eight HFD-responsive lncRNAs and three metformin-responsive lncRNAs were noted due to their widespread associations with disease genes. Moreover, seven miRNAs that interacted with multiple differentially expressed circRNAs were highlighted because they were likely to be associated with metabolic or liver diseases. The present study identified novel changes in the coding transcriptome and non-coding RNAs in the livers of NAFLD mice after metformin treatment that might shed light on the underlying mechanism by which metformin impedes the progression of NAFLD. © 2018 The Author(s). Published by S. Karger AG, Basel.

  6. Esculetin ameliorates hepatic fibrosis in high fat diet induced non-alcoholic fatty liver disease by regulation of FoxO1 mediated pathway.

    Pandey, Anuradha; Raj, Priyank; Goru, Santosh Kumar; Kadakol, Almesh; Malek, Vajir; Sharma, Nisha; Gaikwad, Anil Bhanudas

    2017-08-01

    Non-alcoholic fatty liver disease (NAFLD), a chronic metabolic disorder is associated with oxidative stress, inflammation and fibrotic cascades. In this study, we aimed to examine the effects of Esculetin, a well-known anti-oxidant on TGF-β1 mediated liver fibrosis and FoxO1 activity. A non-genetic murine model for NAFLD was developed by chronic high fat diet (HFD) (58% calories from fats) feeding in Wistar rats. The plasma biochemical parameters, liver function tests, oxidative stress, and histopathological alterations were assessed. The alterations in extracellular matrix (ECM) deposition and FoxO1 activity were assessed by immunohistochemistry. The aberrations in plasma parameters, liver functioning, morphometric and microscopic changes in liver structure of HFD fed rats were significantly improved by treatment with Esculetin. Liver fibrosis, identified in the form of collagen deposition and expression of fibrotic proteins like TGF-β1 and fibronectin was also markedly controlled by Esculetin. The expression of phospho-FoxO1 was found to be reduced in HFD fed rats' liver, showing an increase in activation of FoxO1 under insulin resistant and hyperglycemic states. Esculetin treatment could improve phospho-FoxO1 expression, thus showing its ability to act on Akt/PI3K/FoxO1 pathway. As per the previous studies, a potential therapy for NAFLD may be the one with multi-faceted actions on insulin resistance, oxidative stress, inflammation and fibrosis. This study demonstrates the efficiency of Esculetin in improving liver fibrosis in HFD induced NAFLD. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  7. Inhalation exposure to white spirit causes region-dependent alterations in the levels of glial fibrillary acidic protein

    Lam, Henrik Rye; Ladefoged, Ole; østergaard, G.

    2000-01-01

    Enhanced expression of glial fibrillary acidic protein (GFAP) is known to be associated with toxicant-induced gliosis, a homotypic response of the central nervous system to neural injury. A variety of neurochemical and neurophysiological effects have been observed in experimental animals exposed ...

  8. Alcohol, microbiome, life style influence alcohol and non-alcoholic organ damage.

    Neuman, Manuela G; French, Samuel W; Zakhari, Samir; Malnick, Stephen; Seitz, Helmut K; Cohen, Lawrence B; Salaspuro, Mikko; Voinea-Griffin, Andreea; Barasch, Andrei; Kirpich, Irina A; Thomes, Paul G; Schrum, Laura W; Donohue, Terrence M; Kharbanda, Kusum K; Cruz, Marcus; Opris, Mihai

    2017-02-01

    This paper is based upon the "8th Charles Lieber's Satellite Symposium" organized by Manuela G. Neuman at the Research Society on Alcoholism Annual Meeting, on June 25, 2016 at New Orleans, Louisiana, USA. The integrative symposium investigated different aspects of alcohol-induced liver disease (ALD) as well as non-alcohol-induced liver disease (NAFLD) and possible repair. We revealed the basic aspects of alcohol metabolism that may be responsible for the development of liver disease as well as the factors that determine the amount, frequency and which type of alcohol misuse leads to liver and gastrointestinal diseases. We aimed to (1) describe the immuno-pathology of ALD, (2) examine the role of genetics in the development of alcoholic hepatitis (ASH) and NAFLD, (3) propose diagnostic markers of ASH and non-alcoholic steatohepatitis (NASH), (4) examine age and ethnic differences as well as analyze the validity of some models, (5) develop common research tools and biomarkers to study alcohol-induced effects, 6) examine the role of alcohol in oral health and colon and gastrointestinal cancer and (7) focus on factors that aggravate the severity of organ-damage. The present review includes pre-clinical, translational and clinical research that characterizes ALD and NAFLD. Strong clinical and experimental evidence lead to recognition of the key toxic role of alcohol in the pathogenesis of ALD with simple fatty infiltrations and chronic alcoholic hepatitis with hepatic fibrosis or cirrhosis. These latter stages may also be associated with a number of cellular and histological changes, including the presence of Mallory's hyaline, megamitochondria, or perivenular and perisinusoidal fibrosis. Genetic polymorphisms of ethanol metabolizing enzymes and cytochrome p450 (CYP) 2E1 activation may change the severity of ASH and NASH. Other risk factors such as its co-morbidities with chronic viral hepatitis in the presence or absence of human deficiency virus were discussed

  9. Overview of Alcohol Consumption

    ... of Alcohol Consumption Alcohol's Effects on the Body Alcohol Use Disorder Fetal Alcohol Exposure Support & Treatment Alcohol Policy Special ... experience alcohol’s longer-term effects, which can include: Alcohol use disorder Health problems Increased risk for certain cancers In ...

  10. [Alcohol intake--a two-edged sword. Part 1: metabolism and pathogenic effects of alcohol].

    Ströhle, Alexander; Wolters, Maike; Hahn, Andreas

    2012-08-01

    From the biomedical point of view alcohol is a Janus-faced dietary component with a dose-dependent effect varying from cardiovascular protection to cytotoxicity. Alcohol is absorbed in the upper gastrointestinal tract by passive diffusion, is quickly distributed throughout body water and is mostly eliminated through oxidation. The enzymatically-catalyzed oxidative degradation to acetaldehyde and further to acetate is primarily localized in the liver. In case of a low blood alcohol concentration (0.5 per thousand) are increasingly oxidized by the microsomal ethanoloxidizing system (MEOS). Alcohol consumption induces several metabolic reactions as well as acute effects on the central nervous system. Chronic alcohol consumption to some extent irreparably damages nearly every organ with the liver being particularly concerned. There are three stages of alcohol-induced liver disease (fatty liver, alcohol hepatitis, liver cirrhosis) and the liver damages mainly result from reaction products of alcohol degradation (acetaldehyde, NADH and reactive oxygen species). An especially dreaded clinical complication of the alcohol-induced liver disease is the hepatic encephalopathy. Its pathogenesis is a multifactorial and self-perpetuating process with the swelling of astrocytes being a crucial point. Swollen astrocytes induce several reactions such as oxidative/nitrosative stress, impaired signal transduction, protein modifications and a modified gene expression profile. The swelling of astrocytes and the change in neuronal activity are attributed to several neurotoxins, especially ammonia and aromatic amino acids. In alcohol addicted subjects multiple micronutrient deficiencies are common. The status of folic acid, thiamine, pyridoxine and zinc is especially critical.

  11. Phospholipids as Biomarkers for Excessive Alcohol Use

    2017-03-01

    17. Zhou P, Ross RA, Pywell CM, Liangpunsakul S, Duffield GE. Disturbances in the murine hepatic circadian clock in alcohol-induced hepatic steatosis ...liver disease, alcoholic hepatitis , and alcoholic pancreatitis) among returning veterans at the younger age (~31 years old), compared to previously...Fibrosis in Chronic Hepatitis C Patients: A Systemic Review and Meta- Analysis. J Clin Gastroenterol 2016;50:80-84. 7. Gough G, Heathers L, Puckett D

  12. The methyl donor S-adenosylmethionine prevents liver hypoxia and dysregulation of mitochondrial bioenergetic function in a rat model of alcohol-induced fatty liver disease

    Adrienne L. King

    2016-10-01

    Conclusion: Collectively, these findings indicate that the hepato-protective effects of SAM against alcohol toxicity are mediated, in part, through a mitochondrial mechanism involving preservation of key mitochondrial bioenergetic parameters and the attenuation of hypoxic stress.

  13. Neurobiological Basis of Alcohol Addiction

    Milagros Lisset León Regal

    2014-02-01

    Full Text Available Alcoholism is a serious social problem due to its impact on individual and collective health. In order to provide an update on the latest findings that explain the development and symptoms of alcohol addiction, the short and long term changes that this disorder causes in the central nervous system are shown in this paper. A total of 52 information sources were consulted, including 43 journal articles, 4 books and statistical reports. The main network managers were used. The interaction of ethanol with various structures of the neuronal membrane affects the cytoarchitecture and brain function associated with the reward system, motor processing, learning and memory, resulting in the development of alcohol dependence. In addition, ethanol-induced changes in excitation/inhibition explain the phenomena of alcohol tolerance and withdrawal.

  14. Alcohol-induced decrease in muscle protein synthesis associated with increased binding of mTOR and raptor: Comparable effects in young and mature rats

    Vary Thomas C

    2009-01-01

    Full Text Available Abstract Background Acute alcohol (EtOH intoxication decreases muscle protein synthesis via inhibition of mTOR-dependent translation initiation. However, these studies have been performed in relatively young rapidly growing rats in which muscle protein accretion is more sensitive to growth factor and nutrient stimulation. Furthermore, some in vivo-produced effects of EtOH vary in an age-dependent manner. The hypothesis tested in the present study was that young rats will show a more pronounced decrement in muscle protein synthesis than older mature rats in response to acute EtOH intoxication. Methods Male F344 rats were studied at approximately 3 (young or 12 (mature months of age. Young rats were injected intraperitoneally with 75 mmol/kg of EtOH, and mature rats injected with either 75 or 90 mmol/kg EtOH. Time-matched saline-injected control rats were included for both age groups. Gastrocnemius protein synthesis and the activity of the mTOR pathway were assessed 2.5 h after EtOH using [3H]-labeled phenylalanine and the phosphorylation of various protein factors known to regulate peptide-chain initiation. Results Blood alcohol levels (BALs were lower in mature rats compared to young rats after administration of 75 mmol/kg EtOH (154 ± 23 vs 265 ± 24 mg/dL. However, injection of 90 mmol/kg EtOH in mature rats produced BALs comparable to that of young rats (281 ± 33 mg/dL. EtOH decreased muscle protein synthesis similarly in both young and high-dose EtOH-treated mature rats. The EtOH-induced changes in both groups were associated with a concomitant reduction in 4E-BP1 phosphorylation, and redistribution of eIF4E between the active eIF4E·eIF4G and inactive eIF4E·4EBP1 complex. Moreover, EtOH increased the binding of mTOR with raptor in a manner which appeared to be AMPK- and TSC-independent. In contrast, although muscle protein synthesis was unchanged in mature rats given low-dose EtOH, compared to control values, the phosphorylation of rpS6

  15. Stimulant and motivational effects of alcohol: lessons from rodent and primate models.

    Brabant, Christian; Guarnieri, Douglas J; Quertemont, Etienne

    2014-07-01

    In several animal species including humans, the acute administration of low doses of alcohol increases motor activity. Different theories have postulated that alcohol-induced hyperactivity is causally related to alcoholism. Moreover, a common biological mechanism in the mesolimbic dopamine system has been proposed to mediate the stimulant and motivational effects of alcohol. Numerous studies have examined whether alcohol-induced hyperactivity is related to alcoholism using a great variety of animal models and several animal species. However, there is no review that has summarized this extensive literature. In this article, we present the various experimental models that have been used to study the relationship between the stimulant and motivational effects of alcohol in rodents and primates. Furthermore, we discuss whether the theories hypothesizing a causal link between alcohol-induced hyperactivity and alcoholism are supported by published results. The reviewed findings indicate that animal species that are stimulated by alcohol also exhibit alcohol preference. Additionally, the role of dopamine in alcohol-induced hyperactivity is well established since blocking dopaminergic activity suppresses the stimulant effects of alcohol. However, dopamine transmission plays a much more complex function in the motivational properties of alcohol and the neuronal mechanisms involved in alcohol stimulation and reward are distinct. Overall, the current review provides mixed support for theories suggesting that the stimulant effects of alcohol are related to alcoholism and highlights the importance of animal models as a way to gain insight into alcoholism. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Monascus-fermented red mold dioscorea protects mice against alcohol-induced liver injury, whereas its metabolites ankaflavin and monascin regulate ethanol-induced peroxisome proliferator-activated receptor-γ and sterol regulatory element-binding transcription factor-1 expression in HepG2 cells.

    Cheng, Chih-Fu; Pan, Tzu-Ming

    2018-03-01

    Alcoholic hepatitis is a necroinflammatory process that is associated with fibrosis and leads to cirrhosis in 40% of cases. The hepatoprotective effects of red mold dioscorea (RMD) from Monascus purpureus NTU 568 were evaluated in vivo using a mouse model of chronic alcohol-induced liver disease (ALD). ALD mice were orally administered vehicle (ALD group) or vehicle plus 307.5, 615.0 or 1537.5 mg kg -1 (1 ×, 2 × and 5 ×) RMD for 5 weeks. RMD lowered serum leptin, hepatic total cholesterol, free fatty acid and hepatic triglyceride levels and increased serum adiponectin, hepatic alcohol dehydrogenase and antioxidant enzyme levels. Furthermore, ankaflavin (AK) and monascin (MS), metabolites of RMD fermented with M. purpureus 568, induced peroxisome proliferator-activated receptor-γ expression and the concomitant suppression of ethanol-induced elevation of sterol regulatory element-binding transcription factor-1 and TG in HepG2 cells. These results indicate the hepatoprotective effect of Monascus-fermented RMD. Moreover, AK and MS were identified as the active constituents of RMD for the first time and were shown to protect against ethanol-induced liver damage. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  17. Effect of Chronic Alcohol Consumption on Phosphatidylcholine ...

    2Department of Livestock Products Technology, Rajiv Gandhi Institute of Veterinary Education and Research, ... by alcohol-induced oxidative stress and ..... This work was supported by Konkuk University in. 2013. ... American Family Physician.

  18. Oral Metformin-Ascorbic Acid Co-Administration Ameliorates Alcohol ...

    Oral Metformin-Ascorbic Acid Co-Administration Ameliorates Alcohol-Induced Hepatotoxicity In Rats. ... Nigerian Quarterly Journal of Hospital Medicine ... the present in vivo animal study was to determine whether metformin-ascorbic acid co-administration also prevents alcoholic hepatotoxicity in chronic alcohol exposure.

  19. Alcohol consumption increases locomotion in an open field and induces Fos-immunoreactivity in reward and approach/withdrawal-related neurocircuitries.

    Wscieklica, Tatiana; de Barros Viana, Milena; Le Sueur Maluf, Luciana; Pouza, Kathlein Cristiny Peres; Spadari, Regina Célia; Céspedes, Isabel Cristina

    2016-02-01

    Drug addiction is a chronically relapsing disorder characterized by compulsion to seek and take the drug, loss of control in limiting intake and, eventually, the emergence of a negative emotional state when access to the drug is prevented. Both dopamine and corticotropin-releasing factor (CRF)-mediated systems seem to play important roles in the modulation of alcohol abuse and dependence. The present study investigated the effects of alcohol consumption on anxiety and locomotor parameters and on the activation of dopamine and CRF-innervated brain regions. Male Wistar rats were given a choice of two bottles for 31 days, one containing water and the other a solution of saccharin + alcohol. Control animals only received water and a solution of 0.2% saccharin. On the 31st day, animals were tested in the elevated plus-maze and open field, and euthanized immediately after the behavioral tests. An independent group of animals was treated with ethanol and used to measure blood ethanol concentration. Results showed that alcohol intake did not alter behavioral measurements in the plus-maze, but increased the number of crossings in the open field, an index of locomotor activity. Additionally, alcohol intake increased Fos-immunoreactivity (Fos-ir) in the prefrontal cortex, in the shell region of the nucleus accumbens, in the medial and central amygdala, in the bed nucleus of the stria terminalis, in the septal region, and in the paraventricular and dorsomedial hypothalamus, structures that have been linked to reward and to approach/withdrawal behavior. These observations might be relevant to a better understanding of the behavioral and physiological alterations that follow alcohol consumption. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Ion beam-induced topographical and chemical modification on the poly(styrene-co-allyl alcohol) and its effect on the molecular interaction between the modified surface and liquid crystals

    Jeong, Hae-Chang; Park, Hong-Gyu; Lee, Ju Hwan; Jang, Sang Bok; Oh, Byeong-Yun; Seo, Dae-Shik

    2016-01-01

    We demonstrated uniform liquid crystal (LC) alignment on ion beam (IB)-irradiated poly(styrene-co-allyl alcohol) by modifying the chemical bonding on the surface. An IB-irradiated copolymer was used for the alignment layer. We used physico-chemical analysis to determine the IB-irradiated surface modification and LC alignment mechanism on the surface. During IB treatment on poly(styrene-co-allyl alcohol), IB irradiation induces breaking of chemical bonds on the surface to give rise to new bonds with oxygen atoms. This causes a strong Van der Waals interaction between LCs and the modified surface, thereby resulting in uniform LC alignment. The results of contact angle (CA) studies of the copolymer support the chemical bonding changes that were investigated by XPS. We achieved uniform homogeneous LC alignment and obtained stable electro-optical performance by controlling the IB energy. Therefore, the LC cells with IB-irradiated poly(styrene-co-allyl alcohol) exhibited a good potential for alternative alignment of layers in LC applications.

  1. Ion beam-induced topographical and chemical modification on the poly(styrene-co-allyl alcohol) and its effect on the molecular interaction between the modified surface and liquid crystals

    Jeong, Hae-Chang [Information Display Device Laboratory, Department of Electrical and Electronic Engineering, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-749 (Korea, Republic of); Park, Hong-Gyu [School of Electrical, Electronic & Control Engineering, Changwon National University, 20 Changwondaehak-ro, Uichang-gu, Changwon-si, Gyeongsangnam-do, 51140 (Korea, Republic of); Lee, Ju Hwan; Jang, Sang Bok [Information Display Device Laboratory, Department of Electrical and Electronic Engineering, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-749 (Korea, Republic of); Oh, Byeong-Yun [ZeSHTech Co., Ltd., Business Incubator, Gwangju Institute of Science and Technology, 123, Cheomdangwagi-ro, Buk-gu, Gwangju, 500-712 (Korea, Republic of); Seo, Dae-Shik, E-mail: dsseo@yonsei.ac.kr [Information Display Device Laboratory, Department of Electrical and Electronic Engineering, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-749 (Korea, Republic of)

    2016-10-01

    We demonstrated uniform liquid crystal (LC) alignment on ion beam (IB)-irradiated poly(styrene-co-allyl alcohol) by modifying the chemical bonding on the surface. An IB-irradiated copolymer was used for the alignment layer. We used physico-chemical analysis to determine the IB-irradiated surface modification and LC alignment mechanism on the surface. During IB treatment on poly(styrene-co-allyl alcohol), IB irradiation induces breaking of chemical bonds on the surface to give rise to new bonds with oxygen atoms. This causes a strong Van der Waals interaction between LCs and the modified surface, thereby resulting in uniform LC alignment. The results of contact angle (CA) studies of the copolymer support the chemical bonding changes that were investigated by XPS. We achieved uniform homogeneous LC alignment and obtained stable electro-optical performance by controlling the IB energy. Therefore, the LC cells with IB-irradiated poly(styrene-co-allyl alcohol) exhibited a good potential for alternative alignment of layers in LC applications.

  2. [The catalase inhibitor aminotriazole alleviates acute alcoholic liver injury].

    Ai, Qing; Ge, Pu; Dai, Jie; Liang, Tian-Cai; Yang, Qing; Lin, Ling; Zhang, Li

    2015-02-25

    In this study, the effects of catalase (CAT) inhibitor aminotriazole (ATZ) on alcohol-induced acute liver injury were investigated to explore the potential roles of CAT in alcoholic liver injury. Acute liver injury was induced by intraperitoneal injection of alcohol in Sprague Dawley (SD) rats, and various doses of ATZ (100-400 mg/kg) or vehicle were administered intraperitoneally at 30 min before alcohol exposure. After 24 h of alcohol exposure, the levels of aspartate transaminase (AST), alanine transaminase (ALT) and lactate dehydrogenase (LDH) in plasma were determined. The degree of hepatic histopathological abnormality was observed by HE staining. The activity of hepatic CAT, hydrogen peroxide (H₂O₂) level and malondialdehyde (MDA) content in liver tissue were measured by corresponding kits. The levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in plasma were determined by ELISA method. The results showed that treatment with ATZ dose-dependently suppressed the elevation of ALT, AST and LDH levels induced by alcohol exposure, and that ATZ alleviated alcohol-induced histopathological alterations. Furthermore, ATZ inhibited the activity of CAT, reduced hepatic levels of H₂O₂and MDA in alcohol exposed rats. ATZ also decreased the levels of plasma TNF-α and IL-6 in rats with alcohol exposure. These results indicated that ATZ attenuated alcohol-induced acute liver injury in rats, suggesting that CAT might play important pathological roles in the pathogenesis of alcoholic liver injury.

  3. Alcoholism and Suicide.

    Roy, Alec; Linnoila, Markku

    1986-01-01

    Reviews knowledge about suicide in alcoholism: how commonly suicide among alcoholics occurs; which alcoholics commit suicide and why; suicide among alcoholic women and alcoholic physicians; possible predisposing biological factors; possible linkages with depression, adverse life events, and personality disorder; and future research and directions.…

  4. Alcohol's actions on neuronal nicotinic acetylcholine receptors.

    Davis, Tiffany J; de Fiebre, Christopher M

    2006-01-01

    Although it has been known for many years that alcoholism and tobacco addiction often co-occur, relatively little information is available on the biological factors that regulate the co-use and abuse of nicotine and alcohol. In the brain, nicotine acts at several different types of receptors collectively known as nicotinic acetylcholine receptors (nAChRs). Alcohol also acts on at least some of these receptors, enhancing the function of some nAChR subtypes and inhibiting the activity of others. Chronic alcohol and nicotine administration also lead to changes in the numbers of nAChRs. Natural variations (i.e., polymorphisms) in the genes encoding different nAChR subunits may be associated with individual differences in the sensitivity to some of alcohol's and nicotine's effects. Finally, at least one subtype of nAChR may help protect cells against alcohol-induced neurotoxicity.

  5. Motor performance during and following acute alcohol intoxication in healthy non-alcoholic subjects

    Poulsen, Mette Buch; Jakobsen, Johannes Klitgaard; Andersen, Henning

    2007-01-01

    Chronic alcohol abuse has adverse effects on skeletal muscle, and reduced muscle strength is frequently seen in chronic alcoholics. In this study the acute effects of moderate alcohol intoxication on motor performance was evaluated in 19 non-alcoholic healthy subjects (10 women, 9 men......). A randomised double-blinded placebo controlled design was applied to subjects receiving alcohol in juice and pure juice at two separate test periods. Isokinetic and isometric muscle strength and endurance were determined before, during, 24 and 48 h after the ingestion of alcohol in juice and juice (placebo......). To detect a reduced activation of the central motor pathways superimposed external electrical stimulations during voluntary contractions were applied. Creatine kinase (CK) was measured to detect any alcohol-induced changes in sarcolemmal integrity. No change was seen in isokinetic as well as in isometric...

  6. Current hypotheses on the mechanisms of alcoholism.

    Vetreno, R P; Crews, F T

    2014-01-01

    Chronic use of alcohol results in progressive changes to brain and behavior that often lead to the development of alcohol dependence and alcoholism. Although the mechanisms underlying the development of alcoholism remain to be fully elucidated, diminished executive functioning due to hypoactive prefrontal cortex executive control and hyperactive limbic system anxiety and negative emotion might contribute mechanistically to the shift from experimental use to alcoholism and dependence. In the chapter that follows, behavioral deficits associated with cortical dysfunction and neurodegeneration will be related to the behavioral characteristics of alcoholism (e.g., diminished executive function, impulsivity, altered limbic modulation). We will provide evidence that alterations in cyclic AMP-responsive element binding protein (CREB: neurotrophic) and NF-κB (neuroimmune) signaling contribute to the development and persistence of alcoholism. In addition, genetic predispositions and an earlier age of drinking onset will be discussed as contributing factors to the development of alcohol dependence and alcoholism. Overall chronic ethanol-induced neuroimmune gene induction is proposed to alter limbic and frontal neuronal networks contributing to the development and persistence of alcoholism. © 2014 Elsevier B.V. All rights reserved.

  7. The GABA[subscript A] Receptor Agonist Muscimol Induces an Age- and Region-Dependent Form of Long-Term Depression in the Mouse Striatum

    Zhang, Xiaoqun; Yao, Ning; Chergui, Karima

    2016-01-01

    Several forms of long-term depression (LTD) of glutamatergic synaptic transmission have been identified in the dorsal striatum and in the nucleus accumbens (NAc). Such experience-dependent synaptic plasticity might play important roles in reward-related learning. The GABA[subscript A] receptor agonist muscimol was recently found to trigger a…

  8. Effects of mineral water from spring 3 in Băile Tuşnad on experimentally induced alcoholic liver disease

    Gabriela Dogaru

    2017-05-01

    Full Text Available Chronic alcohol consumption leads to the development of specific disorders, particularly of the liver. In this study, we aimed to investigate by optical microscopy the hepatic changes occurring after administration of ethyl alcohol for 70 days to Wistar rats, as well as the curative effect of mineral water from spring 3 in Băile Tuşnad administered for 50 days after completion of ethyl alcohol administration. Liver fragments were harvested and histologically processed by paraffin embedding and stained with Goldner’s trichrome method. After the first 70 days of the experiment, in the liver parenchyma, fat loading of hepatocytes and mild perivascular fibrosis were identified. After another 50 days, during which some of the rats drank tap water, the pathological evolution did not seem to stop, but on the contrary, a slight aggravation could be observed, while in rats drinking Tuşnad mineral water there was an arrest of evolution and a slight regression of the described aspects. This study evidences the curative effect of mineral water from spring 3 in Băile Tuşnad on alcoholic liver disease.

  9. Chronic alcohol intake promotes tumor growth in a diethylnitrosamine-induced hepatocarcinogenesis mouse model through increased Wnt/Beta-catenin signaling

    Ethanol (EtOH) metabolism is involved in both initiating and promoting mechanisms in hepatocellular carcinoma progression in chronic alcoholics. In this study, we developed a mouse model to test the hypothesis that chronic EtOH consumption promotes tumor growth irrespective of EtOH-related initiati...

  10. Benzyl alcohol induces a reversible fragmentation of the Golgi apparatus and inhibits membrane trafficking between endosomes and the trans-Golgi network

    Simm, Roger; Kvalvaag, Audun Sverre; van Deurs, Bo

    2017-01-01

    Benzyl alcohol (BnOH) is widely used as a component of foods, cosmetics, household products and medical products. It is generally considered to be safe for human use, however, it has been connected to a number of adverse effects, including hypersensitivity reactions and neonatal deaths. Bn...

  11. Tobacco carcinogen (NNK) induces both lung cancer and non-alcoholic steatohepatitis and hepatocellular carcinomas in ferrets which can be attenuated by lycopene supplementation

    Early epidemiologic studies have reported that tobacco smoking, which is causally associated with liver cancer, is an independent risk factor for non-alcoholic fatty liver diseases (NAFLD). Lycopene from tomatoes has been shown to be a potential preventive agent against NAFLD and hepatocellular carc...

  12. Alcoholic Liver Disease

    ... may be increased in women because their digestive system may be less able to process alcohol, thus increasing the amount of alcohol reaching the liver. Genetic makeup Genetic makeup is thought to be involved because alcoholic liver disease often ...

  13. Alcohol Use Screening

    ... Depression Screening Substance Abuse Screening Alcohol Use Screening Alcohol Use Screening (AUDIT-C) - Instructions The following questions ... this tool, there is also text-only version . Alcohol Use Screening (AUDIT-C) - Manual Instructions The following ...

  14. Alcohol Use Disorders

    ... alcohol use disorder” or AUD. AUD is a chronic relapsing brain disease characterized by compulsive alcohol use, loss of control over alcohol intake, and a negative emotional state when not using. ...

  15. Fetal Alcohol Spectrum Disorders (FASDs): Alcohol Use Quiz

    ... Links to Other Websites About Us More CDC Alcohol Topics CDC Alcohol Portal Excessive Alcohol Use Binge ... of alcohol screening and counseling for all women Alcohol Use Quiz Recommend on Facebook Tweet Share Compartir ...

  16. Reversal of alcohol dependence-induced deficits in cue-guided behavior via mGluR2/3 signaling in mice.

    Barker, Jacqueline M; Lench, Daniel H; Chandler, L Judson

    2016-01-01

    Alcohol use disorders are associated with deficits in adaptive behavior. While some behavioral impairments that are associated with alcohol use disorders may predate exposure to drugs of abuse, others may result directly from exposure to drugs of abuse, including alcohol. Identifying a causal role for how alcohol exposure leads to these impairments will enable further investigation of the neurobiological mechanisms by which it acts to dysregulate adaptive behavior. In the present study, we examined the effects of chronic intermittent ethanol exposure (CIE) on the use of reward-paired cues to guide consummatory behaviors in a mouse model, and further, how manipulations of mGluR2/3 signaling-known to be dysregulated after chronic alcohol exposure-may alter the expression of this behavior. Adult male C57B/6J mice were trained to self-administer 10 % ethanol and exposed to CIE via vapor inhalation. After CIE exposure, mice were trained in a Pavlovian task wherein a cue (tone) was paired with the delivery of a 10 % sucrose unconditioned stimulus. The use of the reward-paired cue to guide licking behavior was determined across training. The effect of systemic mGluR2/3 manipulation on discrimination between cue-on and cue-off intervals was assessed by administration of the mGluR2/3 agonist LY379268 or the antagonist LY341495 prior to a testing session. Exposure to CIE resulted in reductions in discrimination between cue-on and cue-off intervals, with CIE-exposed mice exhibiting significantly lower consummatory behavior during reward-paired cues than air controls. In addition, systemic administration of an mGluR2/3 agonist restored the use of reward-paired cues in CIE-exposed animals without impacting behavior in air controls. Conversely, administration of an mGluR2/3 antagonist mimicked the effects of CIE on cue-guided licking behavior, indicating that mGluR2/3 signaling can bidirectionally regulate the ability to use reward-paired cues to guide behavior. Together

  17. Inaccessibility of alcohol-induced cirrhosis of the liver to radiopharmaceutical methods of investigation. Fehlende Leberdarstellung im Szintigramm bei alkoholischer Leberzirrhose

    Roh, T G

    1983-12-08

    Three cases of chronic alcohol abuse are described where the scintigrams recorded completely failed to visualise the hepatic structures. The female patients included in the study abused alcohol over a period of several years and the quantities consumed were far above the dose generally believed to cause cirrhosis in women. All of them displayed signs of advanced cirrhosis of the liver like portal hypertension, icterus, coagulation disorders, hepatic encephalopathy, etc. and the disease eventually led to the death of the patients. Hepatic scintiscanning was performed using Au198, Hg197, Tc99m sulfur colloid, Tc99m antimonial colloid as well as rose bengal iodine 131 tagged isotope; one patient was additionally subjected to radionuclide examination of the abdominal cavity. The causes of the described phenomenon still remain obscure. Damage to the reticuloendothelial system appears to be one of the predominant factors in the etiology of the disease. (TRV).

  18. Treatment of Anxiety Disorders and Comorbid Alcohol Abuse with Buspirone in a Patient with Antidepressant-Induced Platelet Dysfunction: A Case Report

    Mir Mazhar

    2013-01-01

    Full Text Available The risk of abnormal bleeding with serotonin reuptake inhibitors has been known, but there is insufficient evidence base to guide pharmacological treatment of anxiety in patients with underlying haematological conditions. The following case report is about a 50-year-old female with generalized anxiety disorder, social phobia, obsessive compulsive disorder, and alcohol abuse where pharmacological treatment of anxiety symptoms has been difficult as it would lead to bruising due to the patient’s underlying qualitative platelet dysfunction. Treatment with venlafaxine, citalopram, escitalopram, and clomipramine resulted in improvement and anxiety symptoms, as well as reduction in alcohol use, but pharmacological treatment has to be discontinued because of bruising and hematomas. In view of an active substance use disorder, benzodiazepines were avoided as a treatment option. The patient’s anxiety symptoms and comorbid alcohol abuse responded well to pharmacological treatment with buspirone which gradually titrated up to a dose of 30 mg BID. Patient was followed for around a six-month period while she was on buspirone before being discharged to family doctor’s care. Buspirone is unlikely to have a significant effect on platelet serotonin transponder and could be an effective alternative for pharmacological treatment of anxiety in patients with a bleeding diathesis.

  19. Preventive effects of indole-3-carbinol against alcohol-induced liver injury in mice via antioxidant, anti-inflammatory, and anti-apoptotic mechanisms: Role of gut-liver-adipose tissue axis.

    Choi, Youngshim; Abdelmegeed, Mohamed A; Song, Byoung-Joon

    2018-05-01

    Indole-3-carbinol (I3C), found in Brassica family vegetables, exhibits antioxidant, anti-inflammatory, and anti-cancerous properties. Here, we aimed to evaluate the preventive effects of I3C against ethanol (EtOH)-induced liver injury and study the protective mechanism(s) by using the well-established chronic-plus-binge alcohol exposure model. The preventive effects of I3C were evaluated by conducting various histological, biochemical, and real-time PCR analyses in mouse liver, adipose tissue, and colon, since functional alterations of adipose tissue and intestine can also participate in promoting EtOH-induced liver damage. Daily treatment with I3C alleviated EtOH-induced liver injury and hepatocyte apoptosis, but not steatosis, by attenuating elevated oxidative stress, as evidenced by the decreased levels of hepatic lipid peroxidation, hydrogen peroxide, CYP2E1, NADPH-oxidase, and protein acetylation with maintenance of mitochondrial complex I, II, and III protein levels and activities. I3C also restored the hepatic antioxidant capacity by preventing EtOH-induced suppression of glutathione contents and mitochondrial aldehyde dehydrogenase-2 activity. I3C preventive effects were also achieved by attenuating the increased levels of hepatic proinflammatory cytokines, including IL1β, and neutrophil infiltration. I3C also attenuated EtOH-induced gut leakiness with decreased serum endotoxin levels through preventing EtOH-induced oxidative stress, apoptosis of enterocytes, and alteration of tight junction protein claudin-1. Furthermore, I3C alleviated adipose tissue inflammation and decreased free fatty acid release. Collectively, I3C prevented EtOH-induced liver injury via attenuating the damaging effect of ethanol on the gut-liver-adipose tissue axis. Therefore, I3C may also have a high potential for translational research in treating or preventing other types of hepatic injury associated with oxidative stress and inflammation. Copyright © 2017 Elsevier Inc. All

  20. Fetal alcohol syndrome

    ... a baby when a mother drinks alcohol during pregnancy. Causes Using alcohol during pregnancy can cause the same risks as using alcohol in general. But it poses extra risks to the unborn baby. When a pregnant woman drinks ... use during pregnancy. Larger amounts of alcohol appear to increase the ...

  1. Turning to alcohol?

    Reiboro, S.K.

    1998-01-01

    Brazil is examining whether turning to alcohol could solve its problems. The fuel alcohol producers are lobbying hard for the government to increase the use of alcohol to fuel the country's cars. Not only does using alcohol reduce CO 2 , runs the argument, but the Kyoto agreement might just attract international financing for the project. (author)

  2. Clearinghouse: alcohol and poppers.

    1999-03-01

    Ten articles from magazines and journals are referenced on the subjects of alcohol and poppers. Topics include alcohol consumption and HIV/AIDS-related risky sexual behavior, alcohol and drug abuse, and self-esteem, gender, and alcohol use. Contact information is provided.

  3. Children of Alcoholics.

    Krois, Deborah Helen

    Although alcoholism has long been considered a serious problem, the impact of parental alcoholism on children has only recently begun to receive attention from researchers and clinicians. A review of the empirical literature on children of alcoholics was conducted and it was concluded that children raised in an alcoholic family are at increased…

  4. Fetal Alcohol Exposure

    ... categories: 4 » Fetal Alcohol Syndrome (FAS) » Partial FAS (pFAS) » Alcohol-Related Neurodevelopmental Disorder (ARND) » Alcohol-Related Birth ... either prenatally, after birth, or both Partial FAS (pFAS) Partial FAS (pFAS) involves prenatal alcohol exposure, and ...

  5. Internet Alcohol Marketing and Underage Alcohol Use.

    McClure, Auden C; Tanski, Susanne E; Li, Zhigang; Jackson, Kristina; Morgenstern, Matthis; Li, Zhongze; Sargent, James D

    2016-02-01

    Internet alcohol marketing is not well studied despite its prevalence and potential accessibility and attractiveness to youth. The objective was to examine longitudinal associations between self-reported engagement with Internet alcohol marketing and alcohol use transitions in youth. A US sample of 2012 youths aged 15 to 20 was surveyed in 2011. An Internet alcohol marketing receptivity score was developed, based on number of positive responses to seeing alcohol advertising on the Internet, visiting alcohol brand Web sites, being an online alcohol brand fan, and cued recall of alcohol brand home page images. We assessed the association between baseline marketing receptivity and both ever drinking and binge drinking (≥6 drinks per occasion) at 1-year follow-up with multiple logistic regression, controlling for baseline drinking status, Internet use, sociodemographics, personality characteristics, and peer or parent drinking. At baseline, ever-drinking and binge-drinking prevalence was 55% and 27%, respectively. Many (59%) reported seeing Internet alcohol advertising, but few reported going to an alcohol Web site (6%) or being an online fan (3%). Higher Internet use, sensation seeking, having family or peers who drank, and past alcohol use were associated with Internet alcohol marketing receptivity, and a score of 1 or 2 was independently associated with greater adjusted odds of initiating binge drinking (odds ratio 1.77; 95% confidence interval, 1.13-2.78 and odds ratio 2.15; 95% confidence interval, 1.06-4.37 respectively) but not with initiation of ever drinking. Although high levels of engagement with Internet alcohol marketing were uncommon, most underage youths reported seeing it, and we found a prospective association between receptivity to this type of alcohol marketing and future problem drinking, making additional research and ongoing surveillance important. Copyright © 2016 by the American Academy of Pediatrics.

  6. Internet Alcohol Marketing and Underage Alcohol Use

    McClure, Auden C.; Tanski, Susanne E.; Li, Zhigang; Jackson, Kristina; Morgenstern, Matthis; Li, Zhongze; Sargent, James D.

    2016-01-01

    BACKGROUND AND OBJECTIVE Internet alcohol marketing is not well studied despite its prevalence and potential accessibility and attractiveness to youth. The objective was to examine longitudinal associations between self-reported engagement with Internet alcohol marketing and alcohol use transitions in youth. METHODS A US sample of 2012 youths aged 15 to 20 was surveyed in 2011. An Internet alcohol marketing receptivity score was developed, based on number of positive responses to seeing alcohol advertising on the Internet, visiting alcohol brand Web sites, being an online alcohol brand fan, and cued recall of alcohol brand home page images. We assessed the association between baseline marketing receptivity and both ever drinking and binge drinking (≥6 drinks per occasion) at 1-year follow-up with multiple logistic regression, controlling for baseline drinking status, Internet use, sociodemographics, personality characteristics, and peer or parent drinking. RESULTS At baseline, ever-drinking and binge-drinking prevalence was 55% and 27%, respectively. Many (59%) reported seeing Internet alcohol advertising, but few reported going to an alcohol Web site (6%) or being an online fan (3%). Higher Internet use, sensation seeking, having family or peers who drank, and past alcohol use were associated with Internet alcohol marketing receptivity, and a score of 1 or 2 was independently associated with greater adjusted odds of initiating binge drinking (odds ratio 1.77; 95% confidence interval, 1.13–2.78 and odds ratio 2.15; 95% confidence interval, 1.06–4.37 respectively) but not with initiation of ever drinking. CONCLUSIONS Although high levels of engagement with Internet alcohol marketing were uncommon, most underage youths reported seeing it, and we found a prospective association between receptivity to this type of alcohol marketing and future problem drinking, making additional research and ongoing surveillance important. PMID:26738886

  7. Alcohol and Breastfeeding

    Haastrup, Maija Bruun; Pottegård, Anton; Damkier, Per

    2014-01-01

    While the harmful effects of alcohol during pregnancy are well-established, the consequences of alcohol intake during lactation have been far less examined. We reviewed available data on the prevalence of alcohol intake during lactation, the influence of alcohol on breastfeeding......, the pharmacokinetics of alcohol in lactating women and nursing infants and the effects of alcohol intake on nursing infants. A systematic search was performed in PubMed from origin to May 2013, and 41 publications were included in the review. Approximately half of all lactating women in Western countries consume...... alcohol while breastfeeding. Alcohol intake inhibits the milk ejection reflex, causing a temporary decrease in milk yield. The alcohol concentrations in breast milk closely resemble those in maternal blood. The amount of alcohol presented to nursing infants through breast milk is approximately 5...

  8. Cerebrospinal fluid monocyte chemoattractant protein-1 in alcoholics: support for a neuroinflammatory model of chronic alcoholism.

    Umhau, John C; Schwandt, Melanie; Solomon, Matthew G; Yuan, Peixiong; Nugent, Allison; Zarate, Carlos A; Drevets, Wayne C; Hall, Samuel D; George, David T; Heilig, Markus

    2014-05-01

    Liver inflammation in alcoholism has been hypothesized to influence the development of a neuroinflammatory process in the brain characterized by neurodegeneration and altered cognitive function. Monocyte chemoattractant protein-1/chemokine (C-C motif) ligand 2 (MCP-1/CCL2) elevations have been noted in the alcoholic brain at autopsy and may have a role in this process. We studied cerebrospinal fluid (CSF) levels of MCP-1 as well as interleukin-1β and tumor necrosis factor-α in 13 healthy volunteers and 28 alcoholics during weeks 1 and 4 following detoxification. Serum liver enzymes were obtained as markers of alcohol-related liver inflammation. Compared to healthy volunteers, MCP-1 levels were significantly higher in alcoholics both on day 4 and day 25 (p alcohol-induced liver inflammation, as defined by peripheral concentrations of GGT and AST/GOT. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

  9. Ethanol-induced impairment of polyamine homeostasis – A potential cause of neural tube defect and intrauterine growth restriction in fetal alcohol syndrome

    Haghighi Poodeh, Saeid; Alhonen, Leena; Salonurmi, Tuire; Savolainen, Markku J.

    2014-01-01

    Highlights: • Polyamine pools in embryonic and extraembryonic tissues are developmentally regulated. • Alcohol administration perturbs polyamine levels in the tissues with various patterns. • Total absence of polyamines in the embryo head at 9.5 dpc is critical for development. • The deficiency is associated with reduction in endothelial cell sprouting in the head. • Retarded migration of neural crest cells may cause development of neural tube defect. - Abstract: Introduction: Polyamines play a fundamental role during embryogenesis by regulating cell growth and proliferation and by interacting with RNA, DNA and protein. The polyamine pools are regulated by metabolism and uptake from exogenous sources. The use of certain inhibitors of polyamine synthesis causes similar defects to those seen in alcohol exposure e.g. retarded embryo growth and endothelial cell sprouting. Methods: CD-1 mice received two intraperitoneal injections of 3 g/kg ethanol at 4 h intervals 8.75 days post coitum (dpc). The fetal head, trunk, yolk sac and placenta were collected at 9.5 and 12.5 dpc and polyamine concentrations were determined. Results: No measurable quantity of polyamines could be detected in the embryo head at 9.5 dpc, 12 h after ethanol exposure. Putrescine was not detectable in the trunk of the embryo at that time, whereas polyamines in yolk sac and placenta were at control level. Polyamine deficiency was associated with slow cell growth, reduction in endothelial cell sprouting, an altered pattern of blood vessel network formation and consequently retarded migration of neural crest cells and growth restriction. Discussion: Our results indicate that the polyamine pools in embryonic and extraembryonic tissues are developmentally regulated. Alcohol administration, at the critical stage, perturbs polyamine levels with various patterns, depending on the tissue and its developmental stage. The total absence of polyamines in the embryo head at 9.5 dpc may explain why this

  10. Ethanol-induced impairment of polyamine homeostasis – A potential cause of neural tube defect and intrauterine growth restriction in fetal alcohol syndrome

    Haghighi Poodeh, Saeid, E-mail: saeid.haghighi@oulu.fi [Institute of Clinical Medicine, Department of Internal Medicine, and Biocenter Oulu, University of Oulu, Oulu (Finland); Medical Research Center, Oulu University Hospital, Oulu (Finland); Alhonen, Leena [Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, Kuopio (Finland); School of Pharmacy, Biocenter Kuopio, University of Eastern Finland, Kuopio (Finland); Salonurmi, Tuire; Savolainen, Markku J. [Institute of Clinical Medicine, Department of Internal Medicine, and Biocenter Oulu, University of Oulu, Oulu (Finland); Medical Research Center, Oulu University Hospital, Oulu (Finland)

    2014-03-28

    Highlights: • Polyamine pools in embryonic and extraembryonic tissues are developmentally regulated. • Alcohol administration perturbs polyamine levels in the tissues with various patterns. • Total absence of polyamines in the embryo head at 9.5 dpc is critical for development. • The deficiency is associated with reduction in endothelial cell sprouting in the head. • Retarded migration of neural crest cells may cause development of neural tube defect. - Abstract: Introduction: Polyamines play a fundamental role during embryogenesis by regulating cell growth and proliferation and by interacting with RNA, DNA and protein. The polyamine pools are regulated by metabolism and uptake from exogenous sources. The use of certain inhibitors of polyamine synthesis causes similar defects to those seen in alcohol exposure e.g. retarded embryo growth and endothelial cell sprouting. Methods: CD-1 mice received two intraperitoneal injections of 3 g/kg ethanol at 4 h intervals 8.75 days post coitum (dpc). The fetal head, trunk, yolk sac and placenta were collected at 9.5 and 12.5 dpc and polyamine concentrations were determined. Results: No measurable quantity of polyamines could be detected in the embryo head at 9.5 dpc, 12 h after ethanol exposure. Putrescine was not detectable in the trunk of the embryo at that time, whereas polyamines in yolk sac and placenta were at control level. Polyamine deficiency was associated with slow cell growth, reduction in endothelial cell sprouting, an altered pattern of blood vessel network formation and consequently retarded migration of neural crest cells and growth restriction. Discussion: Our results indicate that the polyamine pools in embryonic and extraembryonic tissues are developmentally regulated. Alcohol administration, at the critical stage, perturbs polyamine levels with various patterns, depending on the tissue and its developmental stage. The total absence of polyamines in the embryo head at 9.5 dpc may explain why this

  11. Mechanisms of neuroimmune gene induction in alcoholism.

    Crews, Fulton T; Vetreno, Ryan P

    2016-05-01

    Alcoholism is a primary, chronic relapsing disease of brain reward, motivation, memory, and related circuitry. It is characterized by an individual's continued drinking despite negative consequences related to alcohol use, which is exemplified by alcohol use leading to clinically significant impairment or distress. Chronic alcohol consumption increases the expression of innate immune signaling molecules (ISMs) in the brain that alter cognitive processes and promote alcohol drinking. Unraveling the mechanisms of alcohol-induced neuroimmune gene induction is complicated by positive loops of multiple cytokines and other signaling molecules that converge on nuclear factor kappa-light-chain-enhancer of activated B cells and activator protein-1 leading to induction of additional neuroimmune signaling molecules that amplify and expand the expression of ISMs. Studies from our laboratory employing reverse transcription polymerase chain reaction (RT-PCR) to assess mRNA, immunohistochemistry and Western blot analysis to assess protein expression, and others suggest that ethanol increases brain neuroimmune gene and protein expression through two distinct mechanisms involving (1) systemic induction of innate immune molecules that are transported from blood to the brain and (2) the direct release of high-mobility group box 1 (HMGB1) from neurons in the brain. Released HMGB1 signals through multiple receptors, particularly Toll-like receptor (TLR) 4, that potentiate cytokine receptor responses leading to a hyperexcitable state that disrupts neuronal networks and increases excitotoxic neuronal death. Innate immune gene activation in brain is persistent, consistent with the chronic relapsing disease that is alcoholism. Expression of HMGB1, TLRs, and other ISMs is increased several-fold in the human orbital frontal cortex, and expression of these molecules is highly correlated with each other as well as lifetime alcohol consumption and age of drinking onset. The persistent and

  12. Multiple spontaneous bone infarcts secondary to alcohol abuse

    Wadhwa, S.S.; Mansberg, R.

    1999-01-01

    Alcohol induced spontaneous osteonecrosis is part of the differential diagnosis in patients with history of alcohol abuse and diffuse bone pain. Usually patients have a longer than 10 year history of alcohol abuse prior to the development of osteonecrosis. The femoral head is the commonest site involved, however, involvement of the long bones is also seen. Facial involvement is rarely seen. Fat embolism secondary to coexisting hyperlipidemia has been postulated as a possible cause of osteonecrosis in alcoholics. A case of multifocal spontaneous bone infarction with facial bone involvement in a 34 year old female alcoholic is described. Copyright (1999) The Australian and New Zealand Society of Nuclear Medicine Inc

  13. First-Row-Transition Ion Metals(II-EDTA Functionalized Magnetic Nanoparticles as Catalysts for Solvent-Free Microwave-Induced Oxidation of Alcohols

    Nuno M. R. Martins

    2017-11-01

    Full Text Available A series of first-row transition-metals combined with ethylenediamine tetraacetic acid (EDTA, as metal-based N,O-chelating ligands, at the surface of ferrite magnetic nanoparticles (MNPs was prepared by a co-precipitation method. Those EDTA functionalized MNPs with general formula Fe3O4@EDTA-M2+ [M = Mn2+ (1, Fe2+ (2, Co2+ (3, Ni2+ (4, Cu2+ (5 or Zn2+ (6] were characterized by FTIR (Fourier Transform Infrared spectroscopy, powder XRD (X-ray Diffraction, SEM (Scanning Electron Microscope, EDS (Energy Dispersive Spectrometer, VSM (Vibrating Sample Magnetometer and TGA (Thermal Gravity Analysis. The application of the magnetic NPs towards the microwave-assisted oxidation of several alcohol substrates in a solvent-free medium was evaluated. The influence of reaction parameters such as temperature, time, type of oxidant, and presence of organic radicals was investigated. This study demonstrates that these MNPs can act as efficient catalysts for the conversion of alcohols to the corresponding ketones or aldehydes with high selectivity and yields up to 99% after 2 h of reaction at 110 °C using t-BuOOH as oxidant. Moreover, they have the advantage of being magnetically recoverable catalysts that can be easily recycled in following runs.

  14. The cinnamyl alcohol dehydrogenase (CAD gene family in flax (Linum usitatissimum L.: Insight from expression profiling of cads induced by elicitors in cultured flax cells

    Eom Hee Seung

    2016-01-01

    Full Text Available Cinnamyl alcohol dehydrogenase (CAD is a key enzyme in the biosynthesis of lignin and lignans as it catalyzes the final step of monolignol biosynthesis, using NADPH as a cofactor. In higher plants, CAD is encoded by a multigene family consisting of three major classes. Based on the recently released flax (Linum usitatissimum L. whole-genome sequences, in this study we identified six CAD family genes that contain an ADH_N domain and an ADH_zinc_N domain, which suggests that the putative flax CADs (LuCADs are zinc-dependent alcohol dehydrogenases and members of the plant CAD family. In addition, expression analysis using quantitative real-time PCR revealed spatial variations in the expression of LuCADs in different organs. Comparative analysis between LuCAD enzymatic activity and LuCAD transcripts indicates that the variation of LuCAD enzymatic activities by elicitors is reflected by transcription of LuCADs in flax suspension-cultured cells. Taken together, our genome-wide analysis of CAD genes and the expression profiling of these genes provide valuable information for understanding the function of CADs, and will assist future studies on the physiological role of monolignols associated with plant defense.

  15. Effects of alcohol on the endocrine system.

    Rachdaoui, Nadia; Sarkar, Dipak K

    2013-09-01

    Chronic consumption of a large amount of alcohol disrupts the communication between nervous, endocrine, and immune system and causes hormonal disturbances that lead to profound and serious consequences at physiologic and behavioral levels. These alcohol-induced hormonal dysregulations affect the entire body and can result in various disorders such as stress abnormalities, reproductive deficits, body growth defect, thyroid problems, immune dysfunction, cancers, bone disease, and psychological and behavioral disorders. This review summarizes the findings from human and animal studies that provide consistent evidence on the various effects of alcohol abuse on the endocrine system. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Mixing an energy drink with an alcoholic beverage increases motivation for more alcohol in college students.

    Marczinski, Cecile A; Fillmore, Mark T; Henges, Amy L; Ramsey, Meagan A; Young, Chelsea R

    2013-02-01

    There has been a dramatic rise in the consumption of alcohol mixed with energy drinks (AmEDs) in social drinkers. It has been suggested that AmED beverages might lead individuals to drink greater quantities of alcohol. This experiment was designed to investigate whether the consumption of AmEDs would alter alcohol priming (i.e., increasing ratings of wanting another drink) compared with alcohol alone. Participants (n = 80) of equal gender attended 1 session where they were randomly assigned to receive 1 of 4 doses (0.91 ml/kg vodka, 1.82 ml/kg energy drink, 0.91 ml/kg vodka mixed with 1.82 ml/kg energy drink [AmED], or a placebo beverage). Alcohol-induced priming of the motivation to drink was assessed by self-reported ratings on the Desire for Drug questionnaire. The priming dose of alcohol increased the subjective ratings of "desire" for more alcohol, consistent with previous research that small doses of alcohol can increase the motivation to drink. Furthermore, higher desire ratings over time were observed with AmEDs compared with alcohol alone. Finally, ratings of liking the drink were similar for the alcohol and AmED conditions. An energy drink may elicit increased alcohol priming. This study provides laboratory evidence that AmED beverages may lead to greater motivation to drink versus the same amount of alcohol consumed alone. Copyright © 2012 by the Research Society on Alcoholism.

  17. Sigma-1 Receptor Mediates Acquisition of Alcohol Drinking and Seeking behavior in Alcohol-Preferring Rats

    Blasio, Angelo; Valenza, Marta; Iyer, Malliga R.; Rice, Kenner C.; Steardo, Luca; Hayashi, T.; Cottone, Pietro; Sabino, Valentina

    2015-01-01

    Sigma-1 receptor (Sig-1R) has been proposed as a novel therapeutic target for drug and alcohol addiction. We have shown previously that Sig-1R agonists facilitate the reinforcing effects of ethanol and induce binge-like drinking, while Sig-1R antagonists block excessive drinking in both genetic and environmental models of alcoholism, without affecting intake in outbred non-dependent rats. Even though significant progress has been made in understanding the function of Sig-1Rs in alcohol reinforcement, its role in the early and late stage of alcohol addiction remains unclear. Administration of the selective Sig-1R antagonist BD-1063 dramatically reduced the acquisition of alcohol drinking behavior as well as the preference for alcohol in genetically selected TSRI Sardinian alcohol preferring (Scr:sP) rats; the treatment had no effect on total fluid intake, food intake or body weight gain, proving selectivity of action. Furthermore, BD-1063 dose-dependently decreased alcohol-seeking behavior in rats trained under a second-order schedule of reinforcement, in which responding is maintained by contingent presentation of a conditioned reinforcer. Finally, an innate elevation in Sig-1R protein levels was found in the nucleus accumbens of alcohol-preferring Scr:sP rats, compared to outbred Wistar rats, alteration which was normalized by chronic, voluntary alcohol drinking. Taken together these findings demonstrate that Sig-1R blockade reduces the propensity to both acquire alcohol drinking and to seek alcohol, and point to the nucleus accumbens as a potential key region for the effects observed. Our data suggest that Sig-1R antagonists may have therapeutic potential in multiple stages of alcohol addiction. PMID:25848705

  18. Acute Alcohol Effects on Narrative Recall and Contextual Memory: An Examination of Fragmentary Blackouts

    Wetherill, Reagan R.; Fromme, Kim

    2011-01-01

    The present study examined the effects of alcohol consumption on narrative recall and contextual memory among individuals with and without a history of fragmentary blackouts in an attempt to better understand why some individuals experience alcohol-induced memory impairments whereas others do not, even at comparable blood alcohol concentrations (BACs). Standardized beverage (alcohol, no alcohol) administration procedures and neuropsychological assessments measured narrative recall and context...

  19. Decreased prefrontal cortical dopamine transmission in alcoholism.

    Narendran, Rajesh; Mason, Neale Scott; Paris, Jennifer; Himes, Michael L; Douaihy, Antoine B; Frankle, W Gordon

    2014-08-01

    Basic studies have demonstrated that optimal levels of prefrontal cortical dopamine are critical to various executive functions such as working memory, attention, inhibitory control, and risk/reward decisions, all of which are impaired in addictive disorders such as alcoholism. Based on this and imaging studies of alcoholism that have demonstrated less dopamine in the striatum, the authors hypothesized decreased dopamine transmission in the prefrontal cortex in persons with alcohol dependence. To test this hypothesis, amphetamine and [11C]FLB 457 positron emission tomography were used to measure cortical dopamine transmission in 21 recently abstinent persons with alcohol dependence and 21 matched healthy comparison subjects. [11C]FLB 457 binding potential, specific compared to nondisplaceable uptake (BPND), was measured in subjects with kinetic analysis using the arterial input function both before and after 0.5 mg kg-1 of d-amphetamine. Amphetamine-induced displacement of [11C]FLB 457 binding potential (ΔBPND) was significantly smaller in the cortical regions in the alcohol-dependent group compared with the healthy comparison group. Cortical regions that demonstrated lower dopamine transmission in the alcohol-dependent group included the dorsolateral prefrontal cortex, medial prefrontal cortex, orbital frontal cortex, temporal cortex, and medial temporal lobe. The results of this study, for the first time, unambiguously demonstrate decreased dopamine transmission in the cortex in alcoholism. Further research is necessary to understand the clinical relevance of decreased cortical dopamine as to whether it is related to impaired executive function, relapse, and outcome in alcoholism.

  20. Global alcohol policy and the alcohol industry.

    Anderson, Peter

    2009-05-01

    The WHO is preparing its global strategy on alcohol, and, in so doing, has been asked to consult with the alcohol industry on ways it could contribute in reducing the harm done by alcohol. This review asks which is more effective in reducing harm: the regulatory approaches that the industry does not favour; or the educational approaches that it does favour. The current literature overwhelmingly finds that regulatory approaches (including those that manage the price, availability, and marketing of alcohol) reduce the risk of and the experience of alcohol-related harm, whereas educational approaches (including school-based education and public education campaigns) do not, with industry-funded education actually increasing the risk of harm. The alcohol industry should not be involved in making alcohol policy. Its involvement in implementing policy should be restricted to its role as a producer, distributor, and marketer of alcohol. In particular, the alcohol industry should not be involved in educational programmes, as such involvement could actually lead to an increase in harm.

  1. Consumo de alcohol alcoholismo

    Rodríguez Páez, Pablo E.; Fundación Valle de Lili

    1999-01-01

    ¿Qué es el alcohol?/¿Cómo actual el alcohol en el organismo?/¿Qué efectos causa?/Efectos por el consumo crónico/¿El consumo de alcohol durante el embarazo afecta el embrión?/¿Qué otras consecuencias tiene el consumo de alcohol?/¿Cuándo se considera que una persona tiene problemas con su consumo de alcohol?/¿Cuándo se debe sospechar que alguien tiene problemas con el consumo de alcohol?/Características del saber beber adecuadamente?/¿Cuales son las alternativas de tratamiento para este problem...

  2. Alcoholic hepatitis.

    Damgaard Sandahl, Thomas

    2014-10-01

    Alcoholic hepatitis (AH) is an acute inflammatory syndrome causing significant morbidity and mortality. The prognosis is strongly dependent on disease severity, as assessed by clinical scoring systems. Reliable epidemiological data as well as knowledge of the clinical course of AH are essential for planning and resource allocation within the health care system. Likewise, individual evaluation of risk is desirable in the clinical handling of patients with AH as it can guide treatment, improve patient information, and serve as strata in clinical trials. The present PhD thesis is based on three studies using a cohort of nearly 2000 patients diagnosed with AH in Denmark from 1999 to 2008 as a cohort, in a population-based study design. The aims of this thesis were as follows. (1) To describe the incidence and short- and long-term mortality, of AH in Denmark (Study I). (2) To validate and compare the ability of the currently available prognostic scores to predict mortality in AH (Study II). (3) To investigate the short- and long-term causes of death of patients with AH (Study III). During the study decade, the annual incidence rate in the Danish population rose from 37 to 46 per 106 for men and from 24 to 34 per 106 for women. Both short- and long-term mortality rose for men and women, and the increase in short-term mortality was attributable to increasing patient age and prevalence of cirrhosis. Our evaluation of the most commonly used prognostic scores for predicting the mortality of patients with AH showed that all scores performed similarly, with Area under the Receiver Operator Characteristics curves giving values between 0.74 and 0.78 for 28-day mortality assessed on admission. Our study on causes of death showed that in the short-term (thesis provides novel warranted epidemiological information about AH that shows increasing incidence and mortality rates. Consequently, it reiterates the fact that AH is a life-threatening disease and suggests that AH is an

  3. Failure of carnitine in improving hepatic nitrogen content in alcoholic and non-alcoholic malnourished rats

    Luciana P. Rodrigues

    2010-01-01

    Full Text Available AIMS: To investigate the effect of carnitine supplementation on alcoholic malnourished rats' hepatic nitrogen content. METHODS: Malnourished rats, on 50% protein-calorie restriction with free access to water (malnutrition group and malnourished rats under the same conditions with free access to a 20% alcohol/water solution (alcohol group were studied. After the undernourishment period (4 weeks with or without alcohol, both groups were randomly divided into two subgroups, one of them nutritionally recovered for 28 days with free access to a normal diet and water (recovery groups and the other re-fed with free access to diet and water plus carnitine (0.1 g/g body weight/day by gavage (carnitine groups. No alcohol intake was allowed during the recovery period. RESULTS: The results showed: i no difference between the alcohol/no alcohol groups, with or without carnitine, regarding body weight gain, diet consumption, urinary nitrogen excretion, plasma free fatty acids, lysine, methionine, and glycine. ii Liver nitrogen content was highest in the carnitine recovery non-alcoholic group (from 1.7 to 3.3 g/100 g, P.05 was highest in the alcoholic animals. CONCLUSION: Carnitine supplementation did not induce better nutritional recovery.

  4. Women and Alcohol

    ... turn JavaScript on. Feature: Rethinking Drinking Women and Alcohol Past Issues / Spring 2014 Table of Contents Women react differently than men to alcohol and face higher risks from it. Pound for ...

  5. Alcohol and Cancer Risk

    ... or more than 14 drinks per week for men. What is the evidence that alcohol drinking is a cause of cancer? Based on extensive reviews of research studies , there is a strong scientific consensus of an association between alcohol drinking ...

  6. Genetics of Alcoholism.

    Zhu, Ena C; Soundy, Timothy J; Hu, Yueshan

    2017-05-01

    Consuming excessive amounts of alcohol has the potential to modify an individual's brain and lead to alcohol dependence. Alcohol use leads to 88,000 deaths every year in the U.S. alone and can lead to other health issues including cancers, such as colorectal cancer, and mental health problems. While drinking behavior varies due to environmental factors, genetic factors also contribute to the risk of alcoholism. Certain genes affecting alcohol metabolism and neurotransmitters have been found to contribute to or inhibit the risk. Geneenvironment interactions may also play a role in the susceptibility of alcoholism. With a better understanding of the different components that can contribute to alcoholism, more personalized treatment could cater to the individual. This review discusses the major genetic factors and some small variants in other genes that contribute to alcoholism, as well as considers the gene-environmental interactions. Copyright© South Dakota State Medical Association.

  7. Children of alcoholics

    Robert Oravecz

    2002-09-01

    Full Text Available The author briefly interprets the research – results, referring to the phenomenon of children of alcoholics, especially the psychological and psychopathological characteristics of children of alcoholics in adolescence and young adulthood. The author presents a screening study of adolescents. The sample contains 200 high school students at age 18. The aim of the survey was to discover the relationship between alcohol consumption of parents, PTSD - related psychopathological symptoms and reported life quality of their children. The study confirmed the hypothesis about a substantial correlation between high alcohol consumption of parents, higher psychopathological symptom - expression and lower reported life quality score of their children. Higher PTSD-related symptomatology in children of alcoholics is probably resulted by home violence, which is very often present in family of alcoholics. The article also evaluated the results regarding suicide ideation of children of alcoholics, which is definitely more frequent and more intense than in their peers living in non alcohol – dependent families.

  8. an Unrecorded Alcohol Beverage

    NICO

    Chemical analysis of volatile compounds fromkhadi, an unrecorded alcoholic beverage from Botswana, was ... quality, some of them may be contaminated and toxic, thereby ... home-brewed alcoholic beverages exist in Botswana and are.

  9. Fetal Alcohol Spectrum Disorders

    Alcohol can harm your baby at any stage during a pregnancy. That includes the earliest stages, before ... can cause a group of conditions called fetal alcohol spectrum disorders (FASDs). Children who are born with ...

  10. Benzyl Alcohol Topical

    Benzyl alcohol lotion is used to treat head lice (small insects that attach themselves to the skin) in adults ... children less than 6 months of age. Benzyl alcohol is in a class of medications called pediculicides. ...

  11. What We Fund - Alcohol

    NCDP

    Analysis of the regulatory environment (national ... Predicting and evaluating policy impact. PA. N ... constrain the use of a holistic approach engaging ... alcohol, and ultra-processed food and drink industries, ... Alcohol and Other Drugs, 2003.

  12. Alcohol Facts and Statistics

    ... Standard Drink? Drinking Levels Defined Alcohol Facts and Statistics Print version Alcohol Use in the United States: ... 1238–1245, 2004. PMID: 15010446 National Center for Statistics and Analysis. 2014 Crash Data Key Findings (Traffic ...

  13. Alcohol use disorder

    ... have problems with alcohol if you: Are a young adult under peer pressure Have depression, bipolar disorder , anxiety disorders , or schizophrenia Can easily obtain alcohol Have low self-esteem Have problems with relationships Live a stressful lifestyle ...

  14. Alcoholism: a systemic proinflammatory condition.

    González-Reimers, Emilio; Santolaria-Fernández, Francisco; Martín-González, María Candelaria; Fernández-Rodríguez, Camino María; Quintero-Platt, Geraldine

    2014-10-28

    Excessive ethanol consumption affects virtually any organ, both by indirect and direct mechanisms. Considerable research in the last two decades has widened the knowledge about the paramount importance of proinflammatory cytokines and oxidative damage in the pathogenesis of many of the systemic manifestations of alcoholism. These cytokines derive primarily from activated Kupffer cells exposed to Gram-negative intestinal bacteria, which reach the liver in supra-physiological amounts due to ethanol-mediated increased gut permeability. Reactive oxygen species (ROS) that enhance the inflammatory response are generated both by activation of Kupffer cells and by the direct metabolic effects of ethanol. The effects of this increased cytokine secretion and ROS generation lie far beyond liver damage. In addition to the classic consequences of endotoxemia associated with liver cirrhosis that were described several decades ago, important research in the last ten years has shown that cytokines may also induce damage in remote organs such as brain, bone, muscle, heart, lung, gonads, peripheral nerve, and pancreas. These effects are even seen in alcoholics without significant liver disease. Therefore, alcoholism can be viewed as an inflammatory condition, a concept which opens the possibility of using new therapeutic weapons to treat some of the complications of this devastating and frequent disease. In this review we examine some of the most outstanding consequences of the altered cytokine regulation that occurs in alcoholics in organs other than the liver.

  15. Isoflavonoid compounds extracted from Pueraria lobata suppress alcohol preference in a pharmacogenetic rat model of alcoholism.

    Lin, R C; Guthrie, S; Xie, C Y; Mai, K; Lee, D Y; Lumeng, L; Li, T K

    1996-06-01

    The extract from an edible vine, Pueraria lobata, has long been used in China to lessen alcohol intoxication. We have previously shown that daidzin, one of the major components from this plant extract, is efficacious in lowering blood alcohol levels and shortens sleep time induced by alcohol ingestion. This study was conducted to test the antidipsotropic effect of daidzin and two other major isoflavonoids, daidzein and puerarin, from Pueraria lobata administered by the oral route. An alcohol-preferring rat model, the selectively-bred P line of rats, was used for the study. All three isoflavonoid compounds were effective in suppressing voluntary alcohol consumption by the P rats. When given orally to P rats at a dose of 100 mg/kg/day, daidzein, daidzin, and puerarin decreased ethanol intake by 75%, 50%, and 40%, respectively. The decrease in alcohol consumption was accompanied by an increase in water intake, so that the total fluid volume consumed daily remained unchanged. The effects of these isoflavonoid compounds on alcohol and water intake were reversible. Suppression of alcohol consumption was evident after 1 day of administration and became maximal after 2 days. Similarly, alcohol preference returned to baseline levels 2 days after discontinuation of the isoflavonoids. Rats receiving the herbal extracts ate the same amounts of food as control animals, and they gained weight normally during the experiments. When administered orally, none of these compounds affected the activities of liver alcohol dehydrogenase and aldehyde dehydrogenase. Therefore, the reversal of alcohol preference produced by these compounds may be mediated via the CNS. Data demonstrate that isoflavonoid compounds extracted from Pueraria lobata is effective in suppressing the appetite for alcohol when taken orally, raising the possibility that other constituents of edible plants may exert similar and more potent actions.

  16. Effects of alcohol on platelet functions.

    Renaud, S C; Ruf, J C

    1996-03-15

    Recent epidemiologic studies have consistently shown that moderate intake of alcoholic beverages protect against morbidity and mortality from coronary heart disease and ischemic stroke. By contrast, alcohol drinking may also predispose to cerebral hemorrhage. These observations suggest an effect of alcohol similar to that of aspirin. Several studies in humans and animals have shown that the immediate effect of alcohol, either added in vitro to platelets or 10 to 20 min after ingestion, is to decrease platelet aggregation in response to most agonists (thrombin, ADP, epinephrine, collagen). Several hours later, as, in free-living populations deprived of drinking since the previous day it is mostly secondary aggregation to ADP and epinephrine and aggregation to collagen that are still inhibited in alcohol drinkers. By contrast, in binge drinkers or in alcoholics after alcohol withdrawal, response to aggregation, especially that induced by thrombin, is markedly increased. This rebound phenomenon, easily reproduced in rats, may explain ischemic strokes or sudden death known to occur after episodes of drunkenness. The platelet rebound effect of alcohol drinking was not observed with moderate red wine consumption in man. The protection afforded by wine has been recently duplicated in rats by grape tannins added to alcohol. This protection was associated with a decrease in the level of conjugated dienes, the first step in lipid peroxidation. In other words, wine drinking does not seem to be associated with the increased peroxidation usually observed with spirit drinking. Although further studies are required, the platelet rebound effect of alcohol drinking could be associated with an excess of lipid peroxides known to increase platelet reactivity, especially to thrombin.

  17. Alcoholism and Lesbians

    Gedro, Julie

    2014-01-01

    This chapter explores the issues involved in the relationship between lesbianism and alcoholism. It examines the constellation of health and related problems created by alcoholism, and it critically interrogates the societal factors that contribute to the disproportionately high rates of alcoholism among lesbians by exploring the antecedents and…

  18. Fuel Class Higher Alcohols

    Sarathy, Mani

    2016-01-01

    This chapter focuses on the production and combustion of alcohol fuels with four or more carbon atoms, which we classify as higher alcohols. It assesses the feasibility of utilizing various C4-C8 alcohols as fuels for internal combustion engines

  19. Alterações no metabolismo da homocisteína induzidas por aguardente de cana-de-açúcar em alcoólatras Homocystein metabolism alterations induced by sugar-cane liquor in alcoholics

    Rogério Nogueira Prioste

    2003-09-01

    , alanine aminotransferase and gamma-glutamyl transpeptidase. There were not alterations in red blood cell count, total protein and hemoglobin corpuscular media concentration. The levels of HCY before treatment are correlated to the FOL (r ² = 0.333. These results suggested that chronic alcoholism is followed by disturbs of sulphur aminoacid metabolism and that the hyperhomocysteinaemia ethanol-induced by sugar-cane liquor may be accompanied by low serum FOL levels that aggrieves the nutritional status of these patients.

  20. Effects of Hydro-alcoholic Extract from Arctium lappa L. (Burdock) Root on Gonadotropins, Testosterone, and Sperm Count and Viability in Male Mice with Nicotinamide/ Streptozotocin-Induced Type 2 Diabetes.

    Ahangarpour, Akram; Oroojan, Ali Akbar; Heidari, Hamid; Ghaedi, Ehsan; Taherkhani, Reza

    2015-01-01

    Reproductive dysfunction is a complication of diabetes. Arctium lappa (burdock) root has hypoglycemic and antioxidative properties, which are traditionally used for treatment of impotence and sterility. Therefore, the aim of this study is to investigate the effects of its hydro alcoholic extract on gonadotropin, testosterone, and sperm parameters in nicotinamide/ streptozotocin-induced diabetic mice. In this experimental study, 56 adult male Naval Medical Research Institute (NMRI) mice (30-35 g) were randomly divided into seven groups: control, diabetes, diabetes + glibenclamide (0.25 mg/kg), diabetes + extract (200 or 300 mg/kg), and extract (200 or 300 mg/kg). Diabetes was induced with intraperitoneal injection of nicotinamide (NA) and streptozotocin (STZ). Twenty-four hours after the last extract and drug administration, serum samples, testes, and cauda epididymis were removed immediately for experimental assessment. Body weight, serum luteinizing hormone (LH), follicle stimulating hormone (FSH), and testosterone levels, and sperm count (P lappa plant has an effect on the health of the reproductive system in order to improve diabetic conditions.

  1. The principal phenolic and alcoholic components of wine protect human lymphocytes against hydrogen peroxide- and ionising radiation-induced DNA damage in vitro

    Fenech, M.; Greenrod, W.

    2003-01-01

    We have tested the hypothesis that the alcoholic and phenolic components of wine are protective against the DNA damaging and cytotoxic effects of hydrogen peroxide and gamma radiation in vitro. The components of wine tested were ethanol, glycerol, a mixture of the phenolic compounds catechin and caffeic acid, and tartaric acid, all at concentrations that were 2.5% or 10.0% of the concentration in a typical Australian white wine Riesling. These components were tested individually or combined as a mixture and compared to a white wine stripped of polyphenols as well as a Hanks balanced salt solution control which was the diluent for the wine components. The effect of the components was tested in lymphocytes, using the cytokinesis-block micronucleus assay, after 30 minutes incubation in plasma or whole blood for the hydrogen peroxide or gamma-radiation challenge respectively. The results obtained showed that ethanol, glycerol, the catechin-caffeic acid mixture, the mixture of all components, and the stripped white wine significantly reduced the DNA damaging effects of hydrogen peroxide and gamma radiation (ANOVA P = 0.043 - 0.001). The strongest protective effect against DNA damage by gamma irradiation was observed for the catechin-caffeic acid mixture and mixture of all components (30% and 32% reduction respectively). These two treatments as well as ethanol produced the strongest protective effects against DNA damage by hydrogen peroxide (24%, 25% and 18% respectively) . The protection provided by the mixture did not account for the expected additive protective effects of the individual components suggesting that the components may be exerting their effects through similar mechanisms which are saturated at the concentrations tested. Ethanol was the only component that significantly increased base-line DNA damage rate, however, this effect was negated in the mixture. In conclusion our results suggest that the main phenolic and alcoholic components of wine can reduce

  2. Reduced alcohol consumption in mice lacking preprodynorphin.

    Blednov, Yuri A; Walker, Danielle; Martinez, Marni; Harris, R Adron

    2006-10-01

    Many studies suggest a role for endogenous opioid peptides and their receptors in regulation of ethanol intake. It is commonly accepted that the kappa-opioid receptors and their endogenous ligands, dynorphins, produce a dysphoric state and therefore may be responsible for avoidance of alcohol. We used mutant mice lacking preprodynorphin in a variety of behavioral tests of alcohol actions. Null mutant female, but not male, mice showed significantly lower preference for alcohol and consumed lower amounts of alcohol in a two-bottle choice test as compared with wild-type littermates. In the same test, knockout mice of both sexes showed a strong reduction of preference for saccharin compared to control mice. In contrast, under conditions of limited (4 h) access (light phase of the light/dark cycle), null mutant mice did not show any differences in consumption of saccharin, but they showed significantly reduced intake of sucrose. To determine the possible cause for reduction of ethanol preference and intake, we studied other ethanol-related behaviors in mice lacking the preprodynorphin gene. There were no differences between null mutant and wild-type mice in ethanol-induced loss of righting reflex, acute ethanol withdrawal, ethanol-induced conditioned place preference, or conditioned taste aversion to ethanol. These results indicate that deletion of preprodynorphin leads to substantial reduction of alcohol intake in female mice, and suggest that this is caused by decreased orosensory reward of alcohol (sweet taste and/or palatability).

  3. Epigenetics—Beyond the Genome in Alcoholism

    Starkman, Bela G.; Sakharkar, Amul J.; Pandey, Subhash C.

    2012-01-01

    Genetic and environmental factors play a role in the development of alcoholism. Whole-genome expression profiling has highlighted the importance of several genes that may contribute to alcohol abuse disorders. In addition, more recent findings have added yet another layer of complexity to the overall molecular mechanisms involved in a predisposition to alcoholism and addiction by demonstrating that processes related to genetic factors that do not manifest as DNA sequence changes (i.e., epigenetic processes) play a role. Both acute and chronic ethanol exposure can alter gene expression levels in specific neuronal circuits that govern the behavioral consequences related to tolerance and dependence. The unremitting cycle of alcohol consumption often includes satiation and self-medication with alcohol, followed by excruciating withdrawal symptoms and the resultant relapse, which reflects both the positive and negative affective states of alcohol addiction. Recent studies have indicated that behavioral changes induced by acute and chronic ethanol exposure may involve chromatin remodeling resulting from covalent histone modifications and DNA methylation in the neuronal circuits involving a brain region called the amygdala. These findings have helped identify enzymes involved in epigenetic mechanisms, such as the histone deacetylase, histone acetyltransferase, and DNA methyltransferase enzymes, as novel therapeutic targets for the development of future pharmacotherapies for the treatment of alcoholism. PMID:23134045

  4. Effect of aqueous and alcoholic extract of Sesbania sesban (Linn Merr. root on glycemic control in streptozotocin-induced diabetic mice

    Manjusha Choudhary

    2014-01-01

    Full Text Available Aim: The present study was carried out to investigate the hypoglycemic effects of the aqueous and ethanolic extracts of Sesbania sesban (SS (Merr. roots, which is widely used in inflammation, fever, ulcers, leucoderma and diabetes in various parts of India. Materials and Methods: SS extracts were administered orally at doses (500 and 1000 mg/kg to normal and streptozotocin (STZ induced Type-2 diabetic mice. The fasting blood glucose (FBG, biochemical parameters in serum viz., blood glucose, serum insulin, cholesterol, triglyceride (TG, high-density lipoprotein (HDL cholesterol, urea, creatinine and total protein, change in body weight, internal organs weight, food intake, water intake and glycogen level in liver were performed for the evaluation of hypoglycemic effects. Results: Both doses of aqueous and ethanolic SS extracts caused a marked decrease of FBG in STZ induced Type-2 diabetic mice. Both extracts decreased the cholesterol, TG, urea, creatinine level and increased the insulin, HDL cholesterol and total protein level. Decrease in body weight and glycogen level induced by STZ was restored. Increase in water and food intake induced by STZ was decreased. Conclusions: The results suggest that aqueous and ethanolic extracts of SS may have hypoglycemic potential for the Type-2 diabetes and support the traditional use of the roots of plant as a hypoglycemic agent.

  5. Genetics and alcoholism.

    Edenberg, Howard J; Foroud, Tatiana

    2013-08-01

    Alcohol is widely consumed; however, excessive use creates serious physical, psychological and social problems and contributes to the pathogenesis of many diseases. Alcohol use disorders (that is, alcohol dependence and alcohol abuse) are maladaptive patterns of excessive drinking that lead to serious problems. Abundant evidence indicates that alcohol dependence (alcoholism) is a complex genetic disease, with variations in a large number of genes affecting a person's risk of alcoholism. Some of these genes have been identified, including two genes involved in the metabolism of alcohol (ADH1B and ALDH2) that have the strongest known affects on the risk of alcoholism. Studies continue to reveal other genes in which variants affect the risk of alcoholism or related traits, including GABRA2, CHRM2, KCNJ6 and AUTS2. As more variants are analysed and studies are combined for meta-analysis to achieve increased sample sizes, an improved picture of the many genes and pathways that affect the risk of alcoholism will be possible.

  6. On molybdenum (6) alcoholates

    Turova, N.Ya.; Kessler, V.G.

    1990-01-01

    Synthesis techniques for molybdenum (6) alcoholates of MoO(OR) 4 (1) and MoO 2 (OR) 2 (2) series by means of exchange interaction of corresponding oxychloride with MOR (M=Li, Na) are obtained. These techniques have allowed to prepare 1(R=Me, Et, i-Pr) and 2(R=Me, Et) with 70-98 % yield. Methylates are also prepared at ether interchange of ethylates by methyl alcohol. Metal anode oxidation in corresponding alcohol may be used for 1 synthesis. Physicochemical properties of both series alcoholates, solubility in alcohols in particular, depend on their formation conditions coordination polymerism. Alcoholates of 1 are rather unstable and tend to decomposition up to 2 and ether. It is suggested to introduce NaOR microquantities to stabilize those alcoholates

  7. Alcohol and atherosclerosis

    Tolstrup, Janne; Grønbaek, Morten

    2007-01-01

    Light to moderate alcohol intake is known to have cardioprotective properties; however, the magnitude of protection depends on other factors and may be confined to some subsets of the population. This review focuses on factors that modify the relationship between alcohol and coronary heart disease...... (CHD). The cardioprotective effect of alcohol seems to be larger among middle-aged and elderly adults than among young adults, who do not have a net beneficial effect of a light to moderate alcohol intake in terms of reduced all-cause mortality. The levels of alcohol at which the risk of CHD is lowest...... and the levels of alcohol at which the risk of CHD exceeds the risk among abstainers are lower for women than for men. The pattern of drinking seems important for the apparent cardioprotective effect of alcohol, and the risk of CHD is generally lower for steady versus binge drinking. Finally, there is some...

  8. Alcohol disinhibition of behaviors in C. elegans.

    Stephen M Topper

    Full Text Available Alcohol has a wide variety of effects on physiology and behavior. One of the most well-recognized behavioral effects is disinhibition, where behaviors that are normally suppressed are displayed following intoxication. A large body of evidence has shown that alcohol-induced disinhibition in humans affects attention, verbal, sexual, and locomotor behaviors. Similar behavioral disinhibition is also seen in many animal models of ethanol response, from invertebrates to mammals and primates. Here we describe several examples of disinhibition in the nematode C. elegans. The nematode displays distinct behavioral states associated with locomotion (crawling on land and swimming in water that are mediated by dopamine. On land, animals crawl and feed freely, but these behaviors are inhibited in water. We found that additional behaviors, including a variety of escape responses are also inhibited in water. Whereas alcohol non-specifically impaired locomotion, feeding, and escape responses in worms on land, alcohol specifically disinhibited these behaviors in worms immersed in water. Loss of dopamine signaling relieved disinhibition of feeding behavior, while loss of the D1-like dopamine receptor DOP-4 impaired the ethanol-induced disinhibition of crawling. The powerful genetics and simple nervous system of C. elegans may help uncover conserved molecular mechanisms that underlie alcohol-induced disinhibition of behaviors in higher animals.

  9. The effects of carbonated alcoholic herbal beverage on selected ...

    Aim: Carbonated Alcoholic herbal beverages (CAHB) are a menace in our society as the drink is grossly abused; this study is therefore aimed at investigating the Histomorphological, selected hepatorenal function indices and some hematological parameters effects induced by a Carbonated Alcoholic Herbal Beverage that ...

  10. Models of alcoholic liver disease in rodents: a critical evaluation

    de la M. Hall, P.; Lieber, C.S.; De Carli, L.M.

    2001-01-01

    ) Lieber-DeCarli liquid diet for alcohol-induced liver injury in rats, by C. S. Lieber and L. M. DeCarli; (3) Tsukamoto-French model of alcoholic liver injury, by S. W. French; (4) Animal models to study endotoxin-ethanol interactions, by K. O. Lindros and H. Järveläinen; and (5) Jejunoileal bypass...

  11. Alcohol drinking, mean corpuscular volume of erythrocytes, and alcohol metabolic genotypes in drunk drivers.

    Pavanello, Sofia; Snenghi, Rossella; Nalesso, Alessandro; Sartore, Daniela; Ferrara, Santo Davide; Montisci, Massimo

    2012-02-01

    Regular and irregular abuse of alcohol are global health priorities associated with diseases at multiple sites, including cancer. Mechanisms of diseases induced by alcohol are closely related to its metabolism. Among conventional markers of alcohol abuse, the mean corpuscular volume (MCV) of erythrocytes is prognostic of alcohol-related cancer and its predictivity increases when combined with functional polymorphisms of alcohol dehydrogenase (ADH1B [rs1229984] and ADH1C [rs698]) and the mitochondrial aldehyde dehydrogenase (ALDH2 [rs671]). Whether these genetic variants can influence abuse in alcohol drinking and MCV has never been examined in drunk-driving traffic offenders. We examined 149 drunk drivers, diagnosed as alcohol abusers according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth edition Text Revision (DSM-IV-TR) and enrolled in a probation program, and 257 social drinkers (controls), all Caucasian males. Alcohol intake was assessed according to self-reported drink-units/d and MCV unadjusted and adjusted for age, smoking, and body mass index. Multivariable models were used to compute MCV adjusted means. Genotype analyses were performed by PCR on DNA from blood. The adjusted MCV mean was higher in drunk-driving abusers than in controls (92 vs. 91fL; Pdrunk-driving abusers (P=.008), reported higher drink-units/d (P=.0126), and had larger MCV (P=.035). The rs698 ADH1C and rs671 ALDH2 polymorphisms were not associated with MCV. ADH1B*1/*1 polymorphism is significantly associated with being a drunk-driving abuser, higher alcohol drinking, and MCV enlargement. This suggests that drunk drivers with augmented MCV modulated by the alcohol metabolic ADH1B*1/*1 genotype may be at higher risk of driving incapability and of alcohol-related cancer. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. Age- and brain region-dependent α-synuclein oligomerization is attributed to alterations in intrinsic enzymes regulating α-synuclein phosphorylation in aging monkey brains.

    Chen, Min; Yang, Weiwei; Li, Xin; Li, Xuran; Wang, Peng; Yue, Feng; Yang, Hui; Chan, Piu; Yu, Shun

    2016-02-23

    We previously reported that the levels of α-syn oligomers, which play pivotal pathogenic roles in age-related Parkinson's disease (PD) and dementia with Lewy bodies, increase heterogeneously in the aging brain. Here, we show that exogenous α-syn incubated with brain extracts from older cynomolgus monkeys and in Lewy body pathology (LBP)-susceptible brain regions (striatum and hippocampus) forms higher amounts of phosphorylated and oligomeric α-syn than that in extracts from younger monkeys and LBP-insusceptible brain regions (cerebellum and occipital cortex). The increased α-syn phosphorylation and oligomerization in the brain extracts from older monkeys and in LBP-susceptible brain regions were associated with higher levels of polo-like kinase 2 (PLK2), an enzyme promoting α-syn phosphorylation, and lower activity of protein phosphatase 2A (PP2A), an enzyme inhibiting α-syn phosphorylation, in these brain extracts. Further, the extent of the age- and brain-dependent increase in α-syn phosphorylation and oligomerization was reduced by inhibition of PLK2 and activation of PP2A. Inversely, phosphorylated α-syn oligomers reduced the activity of PP2A and showed potent cytotoxicity. In addition, the activity of GCase and the levels of ceramide, a product of GCase shown to activate PP2A, were lower in brain extracts from older monkeys and in LBP-susceptible brain regions. Our results suggest a role for altered intrinsic metabolic enzymes in age- and brain region-dependent α-syn oligomerization in aging brains.

  13. Interdependence of coenzyme-induced conformational work and binding potential in yeast alcohol and porcine heart lactate dehydrogenases: a hydrogen-deuterium exchange study

    De Weck, Z.; Pande, J.; Kaegi, J.H.R.

    1987-01-01

    Binding of NAD coenzymes to yeast alcohol dehydrogenase (YADH) and porcine heart lactate dehydrogenase (PHLDH) was studied by hydrogen-deuterium exchange with the infrared technique. Conformational changes in the enzymes specific to the coenzymes and their fragments were observed, and the pH dependence of the exchange reaction shows that it conforms to the EX-2 scheme. In both YADH and PHLDH the magnitude of the conformational change as measured by exchange retardation is considerably larger for the NAD + than for NADH. Studies with coenzyme fragments like ADP-ribose, ADP, and AMP also highlight the lack of rigorous correlation between structural features such as charge and size and their influence on exchange behavior. Ternary complexes such as YADH-NAD + -pyrazole, PHLDH-NAD + -oxalate, and PHLDH-NADH-oxamate, which mimic the transition state, have a significantly more pronounced effect on exchange rates than the corresponding binary complexes. The outstanding feature of this study is the demonstration that in the binary enzyme-coenzyme complexes the more loosely bound NAD + is more effective in retarding exchange than the more firmly bound NADH. These differences are attributed to the unequal structural constraints exerted by the two coenzymes upon the enzymes, which translate to unequal expenditure of transconformational work in the formation of the two complexes. The opposing variation in the free energy of binding and the transconformational work expended can be viewed as an unequal partitioning of the net free energy gain resulting from the protein-ligand interaction into a binding term and that required for conformational change

  14. Ethanol modulation of mammalian BK channels in excitable tissues: molecular targets and their possible contribution to alcohol-induced altered behavior

    Alex M. Dopico

    2014-12-01

    Full Text Available In most tissues, the function of calcium- and voltage-gated potassium (BK channels is modified in response to ethanol concentrations reached in human blood during alcohol intoxication. In general, modification of BK current from ethanol-naïve preparations in response to brief ethanol exposure results from changes in channel open probability without modification of unitary conductance or change in BK protein levels in the membrane. Protracted and/or repeated ethanol exposure, however, may evoke changes in BK expression. The final ethanol effect on BK open probability leading to either BK current potentiation or BK current reduction is determined by an orchestration of molecular factors, including levels of activating ligand (cytosolic calcium, BK subunit composition and posttranslational modifications, and the channel’s lipid microenvironment. These factors seem to allosterically regulate a direct interaction between ethanol and a recognition pocket of discrete dimensions recently mapped to the channel-forming (slo1 subunit. Type of ethanol exposure also plays a role in the final BK response to the drug: in several central nervous system regions (e.g., striatum, primary sensory neurons, and supraoptic nucleus, acute exposure to ethanol reduces neuronal excitability by enhancing BK activity. In contrast, protracted or repetitive ethanol administration may alter BK subunit composition and membrane expression, rendering the BK complex insensitive to further ethanol exposure. In neurohypophysial axon terminals, ethanol potentiation of BK channel activity leads to a reduction in neuropeptide release. In vascular smooth muscle, however, ethanol inhibition of BK current leads to cell contraction and vascular constriction.

  15. Estimation from PET data of transient changes in dopamine concentration induced by alcohol: support for a non-parametric signal estimation method

    Constantinescu, C C; Yoder, K K; Normandin, M D; Morris, E D [Department of Radiology, Indiana University School of Medicine, Indianapolis, IN (United States); Kareken, D A [Department of Neurology, Indiana University School of Medicine, Indianapolis, IN (United States); Bouman, C A [Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN (United States); O' Connor, S J [Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN (United States)], E-mail: emorris@iupui.edu

    2008-03-07

    We previously developed a model-independent technique (non-parametric ntPET) for extracting the transient changes in neurotransmitter concentration from paired (rest and activation) PET studies with a receptor ligand. To provide support for our method, we introduced three hypotheses of validation based on work by Endres and Carson (1998 J. Cereb. Blood Flow Metab. 18 1196-210) and Yoder et al (2004 J. Nucl. Med. 45 903-11), and tested them on experimental data. All three hypotheses describe relationships between the estimated free (synaptic) dopamine curves (F{sup DA}(t)) and the change in binding potential ({delta}BP). The veracity of the F{sup DA}(t) curves recovered by nonparametric ntPET is supported when the data adhere to the following hypothesized behaviors: (1) {delta}BP should decline with increasing DA peak time, (2) {delta}BP should increase as the strength of the temporal correlation between F{sup DA}(t) and the free raclopride (F{sup RAC}(t)) curve increases, (3) {delta}BP should decline linearly with the effective weighted availability of the receptor sites. We analyzed regional brain data from 8 healthy subjects who received two [{sup 11}C]raclopride scans: one at rest, and one during which unanticipated IV alcohol was administered to stimulate dopamine release. For several striatal regions, nonparametric ntPET was applied to recover F{sup DA}(t), and binding potential values were determined. Kendall rank-correlation analysis confirmed that the F{sup DA}(t) data followed the expected trends for all three validation hypotheses. Our findings lend credence to our model-independent estimates of F{sup DA}(t). Application of nonparametric ntPET may yield important insights into how alterations in timing of dopaminergic neurotransmission are involved in the pathologies of addiction and other psychiatric disorders.

  16. Low-ω3 Fatty Acid and Soy Protein Attenuate Alcohol-Induced Fatty Liver and Injury by Regulating the Opposing Lipid Oxidation and Lipogenic Signaling Pathways

    Karina Reyes-Gordillo

    2016-01-01

    Full Text Available Chronic ethanol-induced downregulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α and upregulation of peroxisome proliferator-activated receptor gamma coactivator 1-beta (PGC1β affect hepatic lipid oxidation and lipogenesis, respectively, leading to fatty liver injury. Low-ω3 fatty acid (Low-ω3FA that primarily regulates PGC1α and soy protein (SP that seems to have its major regulatory effect on PGC1β were evaluated for their protective effects against ethanol-induced hepatosteatosis in rats fed with Lieber-deCarli control or ethanol liquid diets with high or low ω3FA fish oil and soy protein. Low-ω3FA and SP opposed the actions of chronic ethanol by reducing serum and liver lipids with concomitant decreased fatty liver. They also prevented the downregulation of hepatic Sirtuin 1 (SIRT1 and PGC1α and their target fatty acid oxidation pathway genes and attenuated the upregulation of hepatic PGC1β and sterol regulatory element-binding protein 1c (SREBP1c and their target lipogenic pathway genes via the phosphorylation of 5′ adenosine monophosphate-activated protein kinase (AMPK. Thus, these two novel modulators attenuate ethanol-induced hepatosteatosis and consequent liver injury potentially by regulating the two opposing lipid oxidation and lipogenic pathways.

  17. A study of the prebiotic-like effects of tomato juice consumption in rats with diet-induced non-alcoholic fatty liver disease (NAFLD).

    García-Alonso, F J; González-Barrio, R; Martín-Pozuelo, G; Hidalgo, N; Navarro-González, I; Masuero, D; Soini, E; Vrhovsek, U; Periago, M J

    2017-10-18

    Gut microbiota may play a role in the pathogenesis of NAFLD. We investigated whether tomato juice consumption for 5 weeks could ameliorate high-fat diet-induced alterations in certain intestinal bacterial groups and products arising from their metabolism (short-chain fatty acids and microbial phenolic catabolites). For this, we used a rat model with NAFLD induced by a high-fat diet, involving four experimental groups: NA (standard diet and water), NL (standard diet and tomato juice), HA (high-fat diet and water) and HL (high-fat diet and tomato juice). The onset of NAFLD impacted the gut microbiota profile, reducing the abundance of Bifidobacterium and Lactobacillus and increasing that of Enterobacteriaceae. Also, reduced concentrations of propionate, butyrate and phenolic catabolites and an increased acetate to propionate (Ac : Pr) ratio were observed. Tomato juice intake partially ameliorated high-fat diet-induced disturbances, particularly by increasing Lactobacillus abundance and diminishing the Ac : Pr ratio, suggesting a potential improvement of the metabolic pattern of NAFLD.

  18. Alcohol Alert: Link Between Stress and Alcohol

    ... patients to better address how stress affects their motivation to drink. Early screening also is vital. For ... C.; Hong, K.A.; et al Enhanced negative emotion and alcohol craving, and altered physiological responses following ...

  19. Alcoholism and Alcohol Abuse - Multiple Languages

    ... PDF Strong Family Relationships Can Prevent Alcohol and Drug Use Among Teens - دری (Dari) MP3 Karen Chemical Dependency Taskforce of Minnesota What Is Addiction? - English PDF What Is Addiction? - دری (Dari) PDF ...

  20. Kefir peptides prevent high-fructose corn syrup-induced non-alcoholic fatty liver disease in a murine model by modulation of inflammation and the JAK2 signaling pathway

    Chen, H L; Tsai, T C; Tsai, Y C; Liao, J W; Yen, C C; Chen, C M

    2016-01-01

    Objective: In recent years, people have changed their eating habits, and high-fructose-containing bubble tea has become very popular. High-fructose intake has been suggested to be a key factor that induces non-alcoholic fatty liver disease (NAFLD). Kefir, a fermented milk product composed of microbial symbionts, has demonstrated numerous biological activities, including antibacterial, antioxidant and immunostimulating effects. The present study aims to evaluate the effects of kefir peptides on high-fructose-induced hepatic steatosis and the possible molecular mechanism. Results: An animal model of 30% high-fructose-induced NAFLD in C57BL/6J mice was established. The experiment is divided into the following six groups: (1) normal: H2O drinking water; (2) mock: H2O+30% fructose; (3) KL: low-dose kefir peptides (50 mg kg−1)+30% fructose; (4) KM: medium-dose kefir peptides (100 mg kg−1)+30% fructose; (5) KH: high-dose kefir peptides (150 mg kg−1)+30% fructose; and (6) CFM: commercial fermented milk (100 mg kg−1)+30% fructose. The results show that kefir peptides improve fatty liver syndrome by decreasing body weight, serum alanine aminotransferase, triglycerides, insulin and hepatic triglycerides, cholesterol, and free fatty acids as well as the inflammatory cytokines (TNF-α, IL-6 and IL-1β) that had been elevated in fructose-induced NAFLD mice. In addition, kefir peptides markedly increased phosphorylation of AMPK to downregulate its targeted enzymes, ACC (acetyl-CoA carboxylase) and SREBP-1c (sterol regulatory element-binding protein 1), and inhibited de novo lipogenesis. Furthermore, kefir peptides activated JAK2 to stimulate STAT3 phosphorylation, which can translocate to the nucleus, and upregulated several genes, including the CPT1 (carnitine palmitoyltransferase-1) involved in fatty acid oxidation. Conclusion: Our data have demonstrated that kefir peptides can improve the symptoms of NAFLD, including body weight, energy intake

  1. Kefir peptides prevent high-fructose corn syrup-induced non-alcoholic fatty liver disease in a murine model by modulation of inflammation and the JAK2 signaling pathway.

    Chen, H L; Tsai, T C; Tsai, Y C; Liao, J W; Yen, C C; Chen, C M

    2016-12-12

    In recent years, people have changed their eating habits, and high-fructose-containing bubble tea has become very popular. High-fructose intake has been suggested to be a key factor that induces non-alcoholic fatty liver disease (NAFLD). Kefir, a fermented milk product composed of microbial symbionts, has demonstrated numerous biological activities, including antibacterial, antioxidant and immunostimulating effects. The present study aims to evaluate the effects of kefir peptides on high-fructose-induced hepatic steatosis and the possible molecular mechanism. An animal model of 30% high-fructose-induced NAFLD in C57BL/6J mice was established. The experiment is divided into the following six groups: (1) normal: H 2 O drinking water; (2) mock: H 2 O+30% fructose; (3) KL: low-dose kefir peptides (50 mg kg -1 )+30% fructose; (4) KM: medium-dose kefir peptides (100 mg kg -1 )+30% fructose; (5) KH: high-dose kefir peptides (150 mg kg -1 )+30% fructose; and (6) CFM: commercial fermented milk (100 mg kg -1 )+30% fructose. The results show that kefir peptides improve fatty liver syndrome by decreasing body weight, serum alanine aminotransferase, triglycerides, insulin and hepatic triglycerides, cholesterol, and free fatty acids as well as the inflammatory cytokines (TNF-α, IL-6 and IL-1β) that had been elevated in fructose-induced NAFLD mice. In addition, kefir peptides markedly increased phosphorylation of AMPK to downregulate its targeted enzymes, ACC (acetyl-CoA carboxylase) and SREBP-1c (sterol regulatory element-binding protein 1), and inhibited de novo lipogenesis. Furthermore, kefir peptides activated JAK2 to stimulate STAT3 phosphorylation, which can translocate to the nucleus, and upregulated several genes, including the CPT1 (carnitine palmitoyltransferase-1) involved in fatty acid oxidation. Our data have demonstrated that kefir peptides can improve the symptoms of NAFLD, including body weight, energy intake, inflammatory reaction and the

  2. Alcohol Advertising and Alcohol Consumption by Adolescents

    Henry Saffer; Dhaval Dave

    2003-01-01

    The purpose of this paper is to empirically estimate the effects of alcohol advertising on adolescent alcohol consumption. The theory of brand capital is used to explain the effects of advertising on consumption. The industry response function and the evidence from prior studies indicate that the empirical strategy should maximize the variance in the advertising data. The approach in this paper to maximizing the variance in advertising data is to employ cross sectional data. The Monitoring th...

  3. Alcohol and pregnancy

    Anna Maria Paoletti

    2013-06-01

    Full Text Available Alcohol exerts teratogenic effects in all the gestation times, with peculiar features in relationship to the trimester of pregnancy in which alcohol is assumed. Alcohol itself and its metabolites modify DNA synthesis, cellular division, cellular migration and the fetal development. The characteristic facies of feto-alcoholic syndrome (FAS-affected baby depends on the alcohol impact on skull facial development during the first trimester of pregnancy. In association there are cerebral damages with a strong defect of brain development up to the life incompatibility. Serious consequences on fetal health also depends on dangerous effects of alcohol exposure in the organogenesis of the heart, the bone, the kidney, sensorial organs, et al. It has been demonstrated that maternal binge drinking is a high factor risk of mental retardation and of delinquent behaviour. Unfortunately, a lower alcohol intake also exerts deleterious effects on fetal health. In several countries of the world there is a high alcohol use, and this habit is increased in the women. Therefore, correct information has to be given to avoid alcohol use by women in the preconceptional time and during the pregnancy. Preliminary results of a study performed by the authors show that over 80% of pregnant and puerperal women are not unaware that more than 2 glasses of alcohol/week ingested during pregnancy can create neurological abnormalities in the fetus. However, after the information provided on alcoholic fetopathy, all women are conscious of the damage caused by the use of alcohol to the fetus during pregnancy. This study confirms the need to provide detailed information on the negative effects of alcohol on fetal health. Proceedings of the 9th International Workshop on Neonatology · Cagliari (Italy · October 23rd-26th, 2013 · Learned lessons, changing practice and cutting-edge research

  4. Osteoprotegerin polymorphisms are associated with alcohol ...

    YIZHOU LI

    4The College of Life Sciences, Northwest University, Xi'an, 710069, People's Republic of China ... SNP rs11573856 was considered as a protective effect to the occurrence of alcohol-induced ... the risk of ONFH occurrence, and balanced on osteoclasts– ..... may indirectly bring down the function of negatively regulating.

  5. Osteoprotegerin polymorphisms are associated with alcohol ...

    2016-12-02

    Dec 2, 2016 ... 4The College of Life Sciences, Northwest University, Xi'an, 710069, People's ... study is focussed on OPG gene polymorphisms associated with alcohol-induced ONFH. ... the risk of ONFH occurrence, and balanced on osteoclasts– ..... This work was supported by the National Natural Science Founda-.

  6. Effect of Chronic Alcohol Consumption on Phosphatidylcholine ...

    Purpose: To investigate the correlation between alcohol-induced oxidative stress and tissue phosphatidylcholine hydroperoxide (PC-OOH) content of rat liver and brain. Methods: Ten Wistar rats were divided into two groups: one group was given 20 % ethanol (5 g/kg) and the other the same volume of normal saline, orally ...

  7. Alcohol and atherosclerosis

    Murilo Foppa

    2001-02-01

    Full Text Available Observational studies have attributed a protective effect to alcohol consumption on the development of atherosclerosis and cardiovascular morbidity and mortality. Alcohol intake in the amount of one to two drinks per day results in an estimated 20-40% reduction in cardiovascular events. An additional protective effect, according to major cohort studies, has been attributed to wine, probably due to antioxidant effects and platelet antiaggregation agents. On the other hand, the influence of different patterns of alcohol consumption and environmental factors may explain a great part of the additional effect of wine. Protection may be mediated by modulation of other risk factors, because alcohol increases HDL-C, produces a biphasic response on blood pressure, and modulates the endothelial function, while it neither increases body weight nor impairs glucose-insulin homeostasis. Alcohol may also have a direct effect on atherogenesis. Despite these favorable effects, the current evidence is not enough to justify prescribing alcohol to prevent cardiovascular disease.

  8. Alcohol, aggression, and violence

    Darja Škrila

    2005-09-01

    Full Text Available Background: The association between alcohol and aggression has long been recognized, but the systematic research to understand the causal basis for this relationship and the processes that underlie it has only been undertaken in the past 25 years. In the article the most important mechanisms, by which alcohol affects behavior, are explained. Aggression in persons with alcohol dependence and the connection between antisocial (dissocial personality disorder, alcohol and aggression are described. In addition different forms of aggression or violence, that have been committed under the influence of alcohol, such as inter-partner violence, sexual assault, child abuse, crime and traffic accidents are described.Conclusions: The research findings can be used in the prevention and treatment of alcohol-related aggression.

  9. Alcohol in moderation

    Mueller, Simone; Lockshin, Larry; Louviere, Jordan J.

    2011-01-01

    products identified, which are jointly purchased with low alcohol wines. The effect of a tax increase on substitution patterns between alcoholic beverages is examined. Methodology: In a discrete choice experiment, based on their last purchase, consumers select one or several different alcoholic beverages......Purpose: The study examines the market potential for low and very low alcohol wine products under two different tax regimes. The penetration and market share of low alcohol wine are estimated under both tax conditions. Consumers’ alcoholic beverage purchase portfolios are analysed and those...... into a purchase basket. An experimental design controlled the beverages’ price variation. Applying an intra-individual research design, respondents’ purchases were simulated under current and increased taxes. Findings: A market potential for low and very low wine products of up to ten percent of the wine market...

  10. Antidiabetic, hypolipidemic and hepatoprotective effects of Arctium lappa root’s hydro-alcoholic extract on nicotinamide-streptozotocin induced type 2 model of diabetes in male mice

    Ahangarpour, Akram; Heidari, Hamid; Oroojan, Ali Akbar; Mirzavandi, Farhang; Nasr Esfehani, Khalil; Dehghan Mohammadi, Zeinab

    2017-01-01

    Objective: Arctium lappa (burdock), (A. lappa) root has hypoglycemic and antioxidative effects, and has been used for treatment of diabetes in tradition medicine. This study was conducted to evaluate the antidiabetic and hypolipidemic properties of A. lappa root extract on nicotinamide-streptozotocin (NA-STZ)-induced type2 diabetes in mice. Materials and Methods: In this investigation, 70 adult male NMRI mice (30-35g) randomly divided into 7 groups (n=10) as follow: 1-control, 2-type 2 diabetic mice, 3-diabetic mice that received glibenclamide (0.25 mg/kg) as an anti-diabetic drug, 4, 5, 6 and 7- diabetic and normal animals that were pre-treated with 200 and 300 mg/kg A. lappa root extract, respectively, for 28 days. Diabetes has been induced by intraperitoneal injection of NA and STZ. Finally, the blood sample was taken and insulin, glucose, SGOT, SGPT, alkaline phosphatase, leptin and lipid levels was evaluated. Results: Induction of diabetes decreased the level of insulin, leptin and high density lipoprotein (HDL) and increased the level of other lipids, glucose, and hepatic enzymes significantly (plappa root extract, at specific doses, has an anti-diabetic effect through its hypolipidemic and insulinotropic properties. Hence, this plant extract may be beneficial in the treatment of diabetes. PMID:28348972

  11. Antidiabetic, hypolipidemic and hepatoprotective effects of Arctium lappa root's hydro-alcoholic extract on nicotinamide-streptozotocin induced type 2 model of diabetes in male mice.

    Ahangarpour, Akram; Heidari, Hamid; Oroojan, Ali Akbar; Mirzavandi, Farhang; Nasr Esfehani, Khalil; Dehghan Mohammadi, Zeinab

    2017-01-01

    Arctium lappa (burdock), (A. lappa) root has hypoglycemic and antioxidative effects, and has been used for treatment of diabetes in tradition medicine. This study was conducted to evaluate the antidiabetic and hypolipidemic properties of A. lappa root extract on nicotinamide-streptozotocin (NA-STZ)-induced type2 diabetes in mice. In this investigation, 70 adult male NMRI mice (30-35g) randomly divided into 7 groups (n=10) as follow: 1-control, 2-type 2 diabetic mice, 3-diabetic mice that received glibenclamide (0.25 mg/kg) as an anti-diabetic drug, 4, 5, 6 and 7- diabetic and normal animals that were pre-treated with 200 and 300 mg/kg A. lappa root extract, respectively, for 28 days. Diabetes has been induced by intraperitoneal injection of NA and STZ. Finally, the blood sample was taken and insulin, glucose, SGOT, SGPT, alkaline phosphatase, leptin and lipid levels was evaluated. Induction of diabetes decreased the level of insulin, leptin and high density lipoprotein (HDL) and increased the level of other lipids, glucose, and hepatic enzymes significantly (plappa root extract, at specific doses, has an anti-diabetic effect through its hypolipidemic and insulinotropic properties. Hence, this plant extract may be beneficial in the treatment of diabetes.

  12. Antidiabetic, hypolipidemic and hepatoprotective effects of Arctium lappa root’s hydro-alcoholic extract on nicotinamide-streptozotocin induced type 2 model of diabetes in male mice

    Akram Ahangarpour

    2017-02-01

    Full Text Available Objective: Arctium lappa (burdock, (A. lappa root has hypoglycemic and antioxidative effects, and has been used for treatment of diabetes in tradition medicine. This study was conducted to evaluate the antidiabetic and hypolipidemic properties of A. lappa root extract on nicotinamide-streptozotocin (NA-STZ-induced type2 diabetes in mice.Materials and Methods: In this investigation, 70 adult male NMRI mice (30-35g randomly divided into 7 groups (n=10 as follow: 1-control, 2-type 2 diabetic mice, 3-diabetic mice that received glibenclamide (0.25 mg/kg as an anti-diabetic drug, 4, 5, 6 and 7- diabetic and normal animals that were pre-treated with 200 and 300 mg/kg A. lappa root extract, respectively, for 28 days. Diabetes has been induced by intraperitoneal injection of NA and STZ. Finally, the blood sample was taken and insulin, glucose, SGOT, SGPT, alkaline phosphatase, leptin and lipid levels was evaluated.Results: Induction of diabetes decreased the level of insulin, leptin and high density lipoprotein (HDL and increased the level of other lipids, glucose, and hepatic enzymes significantly (p

  13. Alcohol Consumption in Students

    Tran, Cathy

    2010-01-01

    Drinking behaviour among university students is a serious public health concern. Reasons for drinking are complex and many factors contribute to this behaviour. Previous research has established links between personality factors and alcohol consumption and also between metacognitions and alcohol consumption. Few studies have looked into how personality traits and metacognitions interact. This study investigated the relationships between personality, metacognitions and alcohol consumption in a...

  14. Fetal Alcohol Syndrome "Chemical Genocide."

    Asetoyer, Charon

    In the Northern Plains of the United States, 100% of Indian reservations are affected by alcohol related problems. Approximately 90% of Native American adults are currently alcohol users or abusers or are recovering from alcohol abuse. Alcohol consumption has a devastating effect on the unborn. Fetal Alcohol Syndrome (FAS) is an irreversible birth…

  15. The effect of prior alcohol consumption on the ataxic response to alcohol in high-alcohol preferring mice.

    Fritz, Brandon M; Boehm, Stephen L

    2014-12-01

    We have previously shown that ethanol-naïve high-alcohol preferring (HAP) mice, genetically predisposed to consume large quantities of alcohol, exhibited heightened sensitivity and more rapid acute functional tolerance (AFT) to alcohol-induced ataxia compared to low-alcohol preferring mice. The goal of the present study was to evaluate the effect of prior alcohol self-administration on these responses in HAP mice. Naïve male and female adult HAP mice from the second replicate of selection (HAP2) underwent 18 days of 24-h, 2-bottle choice drinking for 10% ethanol vs. water, or water only. After 18 days of fluid access, mice were tested for ataxic sensitivity and rapid AFT following a 1.75 g/kg injection of ethanol on a static dowel apparatus in Experiment 1. In Experiment 2, a separate group of mice was tested for more protracted AFT development using a dual-injection approach where a second, larger (2.0 g/kg) injection of ethanol was given following the initial recovery of performance on the task. HAP2 mice that had prior access to alcohol exhibited a blunted ataxic response to the acute alcohol challenge, but this pre-exposure did not alter rapid within-session AFT capacity in Experiment 1 or more protracted AFT capacity in Experiment 2. These findings suggest that the typically observed increase in alcohol consumption in these mice may be influenced by ataxic functional tolerance development, but is not mediated by a greater capacity for ethanol exposure to positively influence within-session ataxic tolerance. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Fetal alcohol spectrum disorders: experimental treatments and strategies for intervention.

    Idrus, Nirelia M; Thomas, Jennifer D

    2011-01-01

    Despite the known damaging effects of prenatal alcohol exposure, women continue to drink during pregnancy, creating a need for effective interventions and treatments for fetal alcohol spectrum disorders (FASD). Experimental models can be useful in identifying potential treatments, and this article describes the spectrum of experimental therapeutics that currently are being investigated, including pharmacological, nutritional, and environmental/behavioral interventions. Some treatments target the underlying mechanisms that contribute to alcohol-induced damage, protecting against alcohol's teratogenic effects, whereas other treatments may enhance central nervous system plasticity either during alcohol exposure or long after alcohol exposure has ceased. The insights gained to date from experimental models offer several candidates for attenuating the deficits associated with FASD.

  17. New Insights on Neurobiological Mechanisms underlying Alcohol Addiction

    Cui, Changhai; Noronha, Antonio; Morikawa, Hitoshi; Alvarez, Veronica A.; Stuber, Garret D.; Szumlinski, Karen K.; Kash, Thomas L.; Roberto, Marisa; Wilcox, Mark V.

    2012-01-01

    Alcohol dependence/addiction is mediated by complex neural mechanisms that involve multiple brain circuits and neuroadaptive changes in a variety of neurotransmitter and neuropeptide systems. Although recent studies have provided substantial information on the neurobiological mechanisms that drive alcohol drinking behavior, significant challenges remain in understanding how alcohol-induced neuroadaptations occur and how different neurocircuits and pathways cross-talk. This review article highlights recent progress in understanding neural mechanisms of alcohol addiction from the perspectives of the development and maintenance of alcohol dependence. It provides insights on cross talks of different mechanisms and reviews the latest studies on metaplasticity, structural plasticity, interface of reward and stress pathways, and cross-talk of different neural signaling systems involved in binge-like drinking and alcohol dependence. PMID:23159531

  18. The Effect of Alcohol on Postprandial and Fasting Triglycerides

    Albert Van de Wiel

    2012-01-01

    Full Text Available Alcohol has a significant additive effect on the postprandial triglyceride peak when it accompanies a meal containing fat, especially saturated fat. This results from a decrease in the breakdown of chylomicrons and VLDL remnants due to an acute inhibitory effect of alcohol on lipoprotein lipase activity. Furthermore, alcohol increases the synthesis of large VLDL particles in the liver, which is the main source of triglycerides in the hypertriglyceridemia associated with chronic excessive alcohol intake. In case of chronic consumption, lipoprotein lipase activity seems to adapt itself. The effect of alcohol on adipose tissues is less clear. Sometimes, a severe hypertriglyceridemia induced by alcohol (SHIBA can be observed, especially in patients with type 2 diabetes mellitus and/or obesity increasing the risk of pancreatitis.

  19. Alcohol-related interpretation bias in alcohol-dependent patients

    Woud, M.L.; Pawelczack, S.; Rinck, M.; Lindenmeyer, J.; Souren, P.M.; Wiers, R.W.H.J.; Becker, E.S.

    2014-01-01

    Background Models of addictive behaviors postulate that implicit alcohol-related memory associations and biased interpretation processes contribute to the development and maintenance of alcohol misuse and abuse. The present study examined whether alcohol-dependent patients (AP) show an

  20. Aliphatic alcohols in spirits inhibit phagocytosis by human monocytes.

    Pál, László; Árnyas, Ervin M; Bujdosó, Orsolya; Baranyi, Gergő; Rácz, Gábor; Ádány, Róza; McKee, Martin; Szűcs, Sándor

    2015-04-01

    A large volume of alcoholic beverages containing aliphatic alcohols is consumed worldwide. Previous studies have confirmed the presence of ethanol-induced immunosuppression in heavy drinkers, thereby increasing susceptibility to infectious diseases. However, the aliphatic alcohols contained in alcoholic beverages might also impair immune cell function, thereby contributing to a further decrease in microbicidal activity. Previous research has shown that aliphatic alcohols inhibit phagocytosis by granulocytes but their effect on human monocytes has not been studied. This is important as they play a crucial role in engulfment and killing of pathogenic microorganisms and a decrease in their phagocytic activity could lead to impaired antimicrobial defence in heavy drinkers. The aim of this study was to measure monocyte phagocytosis following their treatment with those aliphatic alcohols detected in alcoholic beverages. Monocytes were separated from human peripheral blood and phagocytosis of opsonized zymosan particles by monocytes treated with ethanol and aliphatic alcohols individually and in combination was determined. It was shown that these alcohols could suppress the phagocytic activity of monocytes in a concentration-dependent manner and when combined with ethanol, they caused a further decrease in phagocytosis. Due to their additive effects, it is possible that they may inhibit phagocytosis in a clinically meaningful way in alcoholics and episodic heavy drinkers thereby contribute to their increased susceptibility to infectious diseases. However, further research is needed to address this question.

  1. Cytological changes in oral epithelium due to Sudanese homemade alcoholic beverages

    Awdah M. Al-hazimi; Shima Bushra Bakhet; Hussain Gadelkarim Ahmed

    2013-01-01

    Introduction and Objective: The aim of this study was to assess the cytological changes in oral epithelium that might be induced by Sudanese homemade alcoholic beverages. Material and methods: Oral Exfoliative Cytology (OEFC) was applied to a case control study to assess the presence and severity of oral epithelial atypia (ET) in 300 subjects (150 alcohol abuse individuals (cases); 150 non-alcohol abuse individuals (controls)). All cases were using homemade alcoholic drinks, locally known as,...

  2. Alcohol advertising and youth.

    Saffer, Henry

    2002-03-01

    The question addressed in this review is whether aggregate alcohol advertising increases alcohol consumption among college students. Both the level of alcohol-related problems on college campuses and the level of alcohol advertising are high. Some researchers have concluded that the cultural myths and symbols used in alcohol advertisements have powerful meanings for college students and affect intentions to drink. There is, however, very little empirical evidence that alcohol advertising has any effect on actual alcohol consumption. The methods used in this review include a theoretical framework for evaluating the effects of advertising. This theory suggests that the marginal effect of advertising diminishes at high levels of advertising. Many prior empirical studies measured the effect of advertising at high levels of advertising and found no effect. Those studies that measure advertising at lower, more disaggregated levels have found an effect on consumption. The results of this review suggest that advertising does increase consumption. However, advertising cannot be reduced with limited bans, which are likely to result in substitution to other available media. Comprehensive bans on all forms of advertising and promotion can eliminate options for substitution and be potentially more effective in reducing consumption. In addition, there is an increasing body of literature that suggests that alcohol counteradvertising is effective in reducing the alcohol consumption of teenagers and young adults. These findings indicate that increased counteradvertising, rather than new advertising bans, appears to be the better choice for public policy. It is doubtful that the comprehensive advertising bans required to reduce advertising would ever receive much public support. New limited bans on alcohol advertising might also result in less alcohol counteradvertising. An important topic for future research is to identify the counteradvertising themes that are most effective with

  3. Alcohol and older drivers' crashes.

    2014-09-01

    Researchers have examined the effects of alcohol consumption : on older adults functioning, and some have : addressed alcohols effects on older drivers crash risk. : Generally, the findings have shown that alcohol is less : likely to be a fa...

  4. Alcohol's Effects on the Body

    ... Effects on the Body Alcohol's Effects on the Body Drinking too much – on a single occasion or ... your health. Here’s how alcohol can affect your body: Brain: Alcohol interferes with the brain’s communication pathways, ...

  5. Protective effect of Calamintha officinalis Moench leaves against alcohol-induced gastric mucosa injury in rats. Macroscopic, histologic and phytochemical analysis.

    Monforte, M T; Lanuzza, F; Pergolizzi, S; Mondello, F; Tzakou, O; Galati, E M

    2012-06-01

    Calamintha officinalis Moench (Lamiaceae) is an aromatic plant used since ancient times for its preservative and medicinal properties. The plant, known as 'Mentuccia' in Central Italy, is used in cooking as an aromatizant and to impart aroma and flavour to food. The methanol extract of the leaves was subjected to phytochemical and biological investigations. The extract contains polyphenols, catechic tannins and terpenes and shows radical scavenger activity. By means of HPLC analysis, eriocitrin, eriodyctiol, acacetin, linarin, benzoic acid and some phenolic acids, such as caffeic, chlorogenic, p-coumaric, were determined. The gastroprotective activity of the extract was investigated using ethanol-induced ulcer in rats, with sucralfate as a reference drug. Samples of gastric mucosa, stained by PAS and haematoxylin/eosin, were observed by light microscopy. The efficacy of the extract was comparable to that of the reference drug. Probably the gastroprotective effect depends on a synergistic action of all the compounds occurring in C. officinalis leaves, even if the antioxidant potential of the leaves plays an important role by removing damaging agents from the gastric mucosa. Copyright © 2011 John Wiley & Sons, Ltd.

  6. Alcohol Use and Hepatitis C

    Peters, Marion G.; Terrault, Norah A.

    2002-01-01

    Excess alcohol consumption can worsen the course and outcome of chronic hepatitis C. It is important to distinguish between alcohol abuse, which must be treated on its own merits, and the effect of alcohol use on progression, severity, and treatment of hepatitis C. Most studies on the effects of alcohol on hepatitis C have focused on patients, with high levels of daily alcohol intake. Indeed, the adverse effects of light and moderate amounts of alcohol intake on hepatitis C virus (HCV) infect...

  7. Drugs and Alcohol

    Scott, Victor F.

    1978-01-01

    Millions of people in this country take medications, and millions drink alcohol. Both are drugs and have effects on the organs and systems with which they or their metabolites come in contact. This short article discusses some of the combined effects of prescribed drugs and alcohol on some systems, with special emphasis on the liver. PMID:712865

  8. Fetal Alcohol Syndrome.

    Zerrer, Peggy

    The paper reviews Fetal Alcohol Syndrome (FAS), a series of effects seen in children whose mothers drink alcohol to excess during pregnancy. The identification of FAS and its recognition as a major health problem in need of prevention are traced. Characteristics of children with FAS are described and resultant growth retardation, abnormal physical…

  9. Alcoholism and Diabetes Mellitus

    Soo-Jeong Kim

    2012-04-01

    Full Text Available Chronic use of alcohol is considered to be a potential risk factor for the incidence of type 2 diabetes mellitus (T2DM, which causes insulin resistance and pancreatic β-cell dysfunction that is a prerequisite for the development of diabetes. However, alcohol consumption in diabetes has been controversial and more detailed information on the diabetogenic impact of alcohol seems warranted. Diabetes, especially T2DM, causes dysregulation of various metabolic processes, which includes a defect in the insulin-mediated glucose function of adipocytes, and an impaired insulin action in the liver. In addition, neurobiological profiles of alcoholism are linked to the effects of a disruption of glucose homeostasis and of insulin resistance, which are affected by altered appetite that regulates the peptides and neurotrophic factors. Since conditions, which precede the onset of diabetes that are associated with alcoholism is one of the crucial public problems, researches in efforts to prevent and treat diabetes with alcohol dependence, receives special clinical interest. Therefore, the purpose of this mini-review is to provide the recent progress and current theories in the interplay between alcoholism and diabetes. Further, the purpose of this study also includes summarizing the pathophysiological mechanisms in the neurobiology of alcoholism.

  10. Alcohol and Choice.

    Kraushaar, Kevin W.

    Increased constraints on access to alcohol resulted from the closure of the sole hotels in two "experimental" towns. This afforded a natural experiment to study the effects of the change in availability of alcohol on consumption. Dependent measures were derived from public records of liquor sales by all licensed premises, and from…

  11. Neurological complications of alcoholism

    I. I. Nikiforov

    2017-01-01

    Full Text Available Nervous system lesions associated with chronic alcohol intoxication are common in clinical practice. They lead to aggravated alcoholic disease, its more frequent recurrences, and intensified pathological craving for alcohol. Neurological pathology in turn occurs with frequent exacerbations. The interaction of diseases, age, and medical  pathomorphism modifies the clinical presentation and course of the  major pathology, as well as comorbidity, the nature and severity of  complications, worsens quality of life in a patient, and makes the  diagnostic and treatment process difficult. The paper discusses the  classification, clinical variants, biochemical and molecular biological  aspects of various complications of alcoholic disease. It considers its  most common form, in particular alcoholic polyneuropathy, as well as its rarer variants, such as hemorrhagic encephalopathy with a subacute course (Gayet–Wernicke encephalopathy.

  12. Pentoxifylline for alcoholic hepatitis

    Whitfield, Kate; Rambaldi, Andrea; Wetterslev, Jørn

    2009-01-01

    BACKGROUND: Alcoholic hepatitis is a life-threatening disease, with an average mortality of approximately 40%. There is no widely accepted, effective treatment for alcoholic hepatitis. Pentoxifylline is used to treat alcoholic hepatitis, but there has been no systematic review to assess its effects....... OBJECTIVES: To assess the benefits and harms of pentoxifylline in alcoholic hepatitis. SEARCH STRATEGY: The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, LILACS......, clinicaltrials.gov, and full text searches were conducted until August 2009. Manufacturers and authors were contacted. SELECTION CRITERIA: All randomised clinical trials of pentoxifylline in participants with alcoholic hepatitis compared to control were selected for inclusion. DATA COLLECTION AND ANALYSIS: Two...

  13. Final report of the safety assessment of Alcohol Denat., including SD Alcohol 3-A, SD Alcohol 30, SD Alcohol 39, SD Alcohol 39-B, SD Alcohol 39-C, SD Alcohol 40, SD Alcohol 40-B, and SD Alcohol 40-C, and the denaturants, Quassin, Brucine Sulfate/Brucine, and Denatonium Benzoate.

    2008-01-01

    produced minimal effects. A spray formula containing 12% SD Alcohol 40-B was found to be nonirritating when evaluated for vaginal mucosal irritation in New Zealand white rabbits. Cosmetic formulations containing SD Alcohol 40-B (denatured with Denatonium Benzoate) were not sensitizers in repeated insult patch tests. A gel formula containing 29% SD Alcohol 40-B and a spray liquid containing 12% SD Alcohol 40-B did not induce photoallergy, dermal sensitization, or phototoxic response in human subjects. Although the absorption of ethanol (aka Alcohol for purposes of cosmetic ingredient labeling) occurs through skin, ethanol does not appear to affect the integrity of the skin barrier nor reach a very high systemic concentration following dermal exposure. Ethanol may be found in the bloodstream as a result of inhalation exposure and ingestion. Topically applied, ethanol can act as a penetration enhancer. Most of the systemic toxicity of ethanol appears to be associated with chronic abuse of alcohol. Although ethanol is denatured to make it unfit for consumption, there have been reports of intentional and unintentional consumption of products containing denatured alcohol. Ethanol is a reproductive and developmental toxicant. Ethanol is genotoxic in some test systems and it has been proposed that the genotoxic effects of ethanol are mediated via its metabolite, acetaldehyde. A brief summary is provided of the effects of chronic ingestion of alcohol including intoxication, liver damage, brain damage, and possible carcinogenicity. The CIR Expert Panel recognizes that certain ingredients in this group are reportedly used in a given product category, but the concentration of use is not available. Because dermal application or inhalation of cosmetic products containing these ingredients will not produce significant systemic exposure to ethanol, the CIR Expert Panel concluded that safety of the ingredients should be predicated on the safety of the denaturants used. The Panel considered

  14. Alcohol, Aldehydes, Adducts and Airways

    Muna Sapkota

    2015-11-01

    Full Text Available Drinking alcohol and smoking cigarettes results in the formation of reactive aldehydes in the lung, which are capable of forming adducts with several proteins and DNA. Acetaldehyde and malondialdehyde are the major aldehydes generated in high levels in the lung of subjects with alcohol use disorder who smoke cigarettes. In addition to the above aldehydes, several other aldehydes like 4-hydroxynonenal, formaldehyde and acrolein are also detected in the lung due to exposure to toxic gases, vapors and chemicals. These aldehydes react with nucleophilic targets in cells such as DNA, lipids and proteins to form both stable and unstable adducts. This adduction may disturb cellular functions as well as damage proteins, nucleic acids and lipids. Among several adducts formed in the lung, malondialdehyde DNA (MDA-DNA adduct and hybrid malondialdehyde-acetaldehyde (MAA protein adducts have been shown to initiate several pathological conditions in the lung. MDA-DNA adducts are pre-mutagenic in mammalian cells and induce frame shift and base-pair substitution mutations, whereas MAA protein adducts have been shown to induce inflammation and inhibit wound healing. This review provides an insight into different reactive aldehyde adducts and their role in the pathogenesis of lung disease.

  15. Alcoholics' selective attention to alcohol stimuli: automated processing?

    Stormark, K M; Laberg, J C; Nordby, H; Hugdahl, K

    2000-01-01

    This study investigated alcoholics' selective attention to alcohol words in a version of the Stroop color-naming task. Alcoholic subjects (n = 23) and nonalcoholic control subjects (n = 23) identified the color of Stroop versions of alcohol, emotional, neutral and color words. Manual reaction times (RTs), skin conductance responses (SCRs) and heart rate (HR) were recorded. Alcoholics showed overall longer RTs than controls while both groups were slower in responding to the incongruent color words than to the other words. Alcoholics showed longer RTs to both alcohol (1522.7 milliseconds [ms]) and emotional words (1523.7 ms) than to neutral words (1450.8 ms) which suggests that the content of these words interfered with the ability to attend to the color of the words. There was also a negative correlation (r = -.41) between RT and response accuracy to alcohol words for the alcoholics, reflecting that the longer time the alcoholics used to respond to the color of the alcohol words, the more incorrect their responses were. The alcoholics also showed significantly greater SCRs to alcohol words (0.16 microSiemens) than to any of the other words (ranging from 0.04-0.08 microSiemens), probably reflecting the emotional significance of the alcohol words. Finally, the alcoholics evidenced smaller HR acceleration to alcohol (1.9 delta bpm) compared to neutral (2.8 delta bpm), which could be related to difficulties alcoholics experience in terminating their attention to the alcohol words. These findings indicate that it is difficult for alcoholics to regulate their attention to alcohol stimuli, suggesting that alcoholics' processing of alcohol information is automated.

  16. Validation of ethnopharmacology of ayurvedic sarasvata ghrita and comparative evaluation of its neuroprotective effect with modern alcoholic and lipid based extracts in β-amyloid induced memory impairment.

    Shelar, Madhuri; Nanaware, Sadhana; Arulmozhi, S; Lohidasan, Sathiyanarayanan; Mahadik, Kakasaheb

    2018-06-12

    Sarasvata ghrita (SG), a polyherbal formulation from ayurveda, an ancient medicinal system of India, has been used to improve intelligence and memory, treat speech delay, speaking difficulties and low digestion power in children. Study aimed to validate the ethno use of SG in memory enhancement through systematic scientific protocol. The effect of SG and modern extracts of ingredients of SG was compared on cognitive function and neuroprotection in amyloid-β peptide 25-35(Aβ25-35) induced memory impairment in wistar rats. Further the underlying mechanism for neuroprotective activity was investigated. SG was prepared as per traditional method, ethanolic extract (EE) was prepared by conventional method and lipid based extract was prepared by modern extraction method. All extracts were standardised by newly developed HPLC method with respect to marker compounds. SG, EE and LE were administered orally to male Wistar rats at doses of 100,200 and 400 mg/kg Body Weight by feeding needle for a period of 21 days after the intracerebroventricular administration of Aβ25-35 bilaterally. Spatial memory of rats was tested using Morris water maze (MWM) and Radial arm maze (RAM) test. The possible underlying mechanisms for the cognitive improvement exhibited by SG, EE and LE was investigated through ex-vivo brain antioxidant effect, monoamine level estimation, acetylcholine esterase (AchE) inhibitory effect and Brain-derived neurotropic factor (BDNF) levels estimation. SG, EE and LE were analyzed by HPLC method, results showed that EE extract has high percent of selected phytoconstituents as compared with SG and LE. SG and LE decrease escape latency and searching distance in a dose dependant manner during MWM test. In case of RAM significant decrease in number of errors and increase in number of correct choices indicate an elevation in retention and recall aspects of learning and memory after administration of SG an LE. SG and LE extract can efficiently prevent accumulation of

  17. CDC Vital Signs: Alcohol Poisoning Deaths

    ... million people, while Alabama has the least. Alcohol dependence (alcoholism) was identified as a factor in 30% ... alcohol content or mixing alcohol with energy drinks. Caffeine can mask alcohol's effects and cause people to ...

  18. Family Based Prevention of Alcohol and Risky Sex for Older Teens

    2018-05-08

    Alcohol Drinking; Alcohol Intoxication; Alcohol Poison; Alcohol-Related Disorders; Alcohol Impairment; Alcohol Withdrawal; Alcohol Abstinence; Alcohol; Harmful Use; Sex Behavior; Sexual Aggression; Sexual Harassment; Relation, Interpersonal

  19. Radiology of the foot in alcoholism

    Scutellari, P.N.; Orzincolo, C.; Lombardo, F.

    1988-01-01

    The authors have reviewed the radiographic patterns of the foot in 28 patients affected by neuropathic joint disease complicating alcoholism, out of a series of 82 chronic ethylic patients. Sixteen of them were also affected by diabetes mellitus. On the basis of X-ray findings, lesion were divided into tree groups, reflecting the evolution of the disease: 1) early changes, especially affecting the soft tissue and joints;2) definite lesions, consisting of fractures, osteolysis, bone destruction and amputation, periarticulardebris; 3)''healing'' signs, simulating degenerative joint disease, which cause severe and weakening deformities. Tabe dorsalis and diabetic osteoarthropathy must be differentiated from alcohol-induced syndrome. Even though a correct differential diagnosis is often difficult to reach, it must be kept in mind that focal/diffuse osteopenia is the most characteristic manifestation of alcoholic osteopathy, whereas different radiographic findings simulate chronic degenerative arthropathies

  20. [Genetic variations in alcohol dehydrogenase, drinking habits and alcoholism

    Tolstrup, J.S.; Rasmussen, S.; Tybjaerg-Hansen, A.

    2008-01-01

    Alcohol is degraded primarily by alcohol dehydrogenase (ADH), and genetic variation that affects the rate of alcohol degradation is found in ADH1B and ADH1C. By genotyping 9,080 white men and women from the general population, we found that men and women with ADH1B slow versus fast alcohol degrad...