A sunlight-induced method for rapid biosynthesis of silver nanoparticles using an Andrachnea chordifolia ethanol extract

Energy Technology Data Exchange (ETDEWEB)

Karimi Zarchi, A.A.; Faridi Majidi, R. [Tehran University of Medical Sciences, Department of Nanomedicine, School of Advanced Medical Technologies, Tehran (Iran, Islamic Republic of); Mokhtari, N.; Shahverdi, A.R. [Tehran University of Medical Sciences, Department of Pharmaceutical Biotechnology and Medicinal Plants Research Center, Faculty of Pharmacy, Tehran (Iran, Islamic Republic of); Arfan, M.; Rehman, T.; Ali, M. [University of Peshawar, Institute of Chemical Sciences, Peshawar, Khyber Pakhtoonkhwa (Pakistan); Amini, M. [Tehran University of Medical Sciences, Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran (Iran, Islamic Republic of)

2011-05-15

In this study a sunlight-induced method for rapid synthesis of silver nanoparticles using an ethanol extract of Andrachnea chordifolia is described. The silver nitrate solutions (1 mM) containing the ethanol extract of Andrachnea chordifolia were irradiated by both sunlight radiation and by sunlight radiation passed through different colored filters (red, yellow or green). The smallest size of silver nanoparticles was obtained when a silver ion solution was irradiated for 5 minutes by direct sunlight radiation. Further examination of the shape and size and of the surface chemistry of these biogenic silver nanoparticles, which were prepared under sunlight radiation, was carried out using transmission electron microscopy and infrared spectroscopy, respectively. Transmission electron microscopy images show spherical particles with an average size of 3.4 nm. Hydroxyl residues were also detected on the surface of these biogenic silver nanoparticles fabricated using plant extract of Andrachnea chordifolia under sunlight radiation. Our study on the reduction of silver ions by this plant extract in darkness shows that the synthesis process can take place under dark conditions at much longer incubations (48 hours). Larger silver polydispersed nanoparticles ranging in size from 3 to 30 nm were obtained when the silver ions were treated with the ethanol extract of Andrachnea chordifolia under dark conditions for 48 hours. (orig.)

Protective effect of tetrahydrocoptisine against ethanol-induced gastric ulcer in mice

International Nuclear Information System (INIS)

Li, Weifeng; Huang, Huimin; Niu, Xiaofeng; Fan, Ting; Mu, Qingli; Li, Huani

2013-01-01

Excessive alcohol consumption can lead to gastric ulcer and the present work was aimed to examine the protective effect of tetrahydrocoptisine (THC) in the model of ethanol-induced gastric ulcer in mice. Fasted mice treated with ethanol 75% (0.5 ml/100 g) were pre-treated with THC (10 or 20 mg/kg, ip), cimetidine (100 mg/kg, ip) or saline in different experimental sets for a period of 3 days, and animals were euthanized 4 h after ethanol ingestion. Gross and microscopic lesions, immunological and biochemical parameters were taken into consideration. The results showed that ethanol induced gastric damage, improving nitric oxide (NO) level, increased pro-inflammatory cytokine (TNF-α and IL-6) levels and myeloperoxidase (MPO) activity, as well as the expression of nuclear factor-κB (NF-κB) in the ethanol group. Pretreatment of THC at doses of 10 and 20 mg/kg bodyweight significantly attenuated the gastric lesions as compared to the ethanol group. These results suggest that the gastroprotective activity of THC is attributed to reducing NO production and adjusting the pro-inflammatory cytokine, inhibited neutrophil accumulation and NF-κB expression. - Highlights: • THC decreased ethanol-induced pro-inflammatory cytokine release. • THC inhibited the production of NO in serum and gastric tissue. • THC reduced NF-κB expression and MPO accumulation in ethanol-induced gastric tissue

Protective effect of tetrahydrocoptisine against ethanol-induced gastric ulcer in mice

Energy Technology Data Exchange (ETDEWEB)

Li, Weifeng, E-mail: liwf@mail.xjtu.edu.cn; Huang, Huimin; Niu, Xiaofeng, E-mail: niuxf@mail.xjtu.edu.cn; Fan, Ting; Mu, Qingli; Li, Huani

2013-10-01

Excessive alcohol consumption can lead to gastric ulcer and the present work was aimed to examine the protective effect of tetrahydrocoptisine (THC) in the model of ethanol-induced gastric ulcer in mice. Fasted mice treated with ethanol 75% (0.5 ml/100 g) were pre-treated with THC (10 or 20 mg/kg, ip), cimetidine (100 mg/kg, ip) or saline in different experimental sets for a period of 3 days, and animals were euthanized 4 h after ethanol ingestion. Gross and microscopic lesions, immunological and biochemical parameters were taken into consideration. The results showed that ethanol induced gastric damage, improving nitric oxide (NO) level, increased pro-inflammatory cytokine (TNF-α and IL-6) levels and myeloperoxidase (MPO) activity, as well as the expression of nuclear factor-κB (NF-κB) in the ethanol group. Pretreatment of THC at doses of 10 and 20 mg/kg bodyweight significantly attenuated the gastric lesions as compared to the ethanol group. These results suggest that the gastroprotective activity of THC is attributed to reducing NO production and adjusting the pro-inflammatory cytokine, inhibited neutrophil accumulation and NF-κB expression. - Highlights: • THC decreased ethanol-induced pro-inflammatory cytokine release. • THC inhibited the production of NO in serum and gastric tissue. • THC reduced NF-κB expression and MPO accumulation in ethanol-induced gastric tissue.

Vitamin-C protect ethanol induced apoptotic neuro degeneration in postnatal rat brain

International Nuclear Information System (INIS)

Naseer, M.I.; Najeebullah; Ikramullah; Zubair, H.; Hassan, M.; Yang, B.C.

2010-01-01

Objective: To evaluate ethanol effects to induced activation of caspsae-3, and to observe the protective effects of Vitamin C (vit-C) on ethanol-induced apoptotic neuro degeneration in rat cortical area of brain. Methodology: Administration of a single dose of ethanol in 7-d postnatal (P7) rats triggers activation of caspase-3 and widespread apoptotic neuronal death. Western blot analysis, cells counting and Nissl staining were used to elucidate possible protective effect of vit-C against ethanol-induced apoptotic neuro degeneration in brain. Results: The results showed that ethanol significantly increased caspase-3 expression and neuronal apoptosis. Furthermore, the co-treatment of vit-C along with ethanol showed significantly decreased expression of caspase-3 as compare to control group. Conclusion: Our findings indicate that vit-C can prevent some of the deleterious effect of ethanol on developing rat brain when given after ethanol exposure and can be used as an effective protective agent for Fetal Alcohol Syndrome (FAS). (author)

Ethanol-induced increase in portal blood glow: Role of adenosine

International Nuclear Information System (INIS)

Orrego, H.; Carmichael, F.J.; Saldivia, V.; Giles, H.G.; Sandrin, S.; Israel, Y.

1988-01-01

The mechanism by which ethanol induces an increase in portal vein blood flow was studied in rats using radiolabeled microspheres. Ethanol by gavage resulted in an increase of 50-70% in portal vein blood flow. The ethanol-induced increase in portal blood flow was suppressed by the adenosine receptor blocker 8-phenyltheophylline. By itself, 8-phenyltheophylline was without effect on cardiac output or portal blood flow. Adenosine infusion resulted in a dose-dependent increase in portal blood flow. This adenosine-induced increase in portal blood flow was inhibited by 8-phenyltheophylline in a dose-dependent manner. Both alcohol and adenosine significantly reduced preportal vascular resistance by 40% and 60%, respectively. These effects were fully suppressed by 8-phenyltheophylline. It is concluded that adenosine is a likely candidate to mediate the ethanol-induced increase in portal vein blood flow. It is suggested that an increase in circulating acetate and liver hypoxia may mediate the effects of alcohol by increasing tissue and interstitial adenosine levels

Mitochondrial permeability transition pore inhibitors prevent ethanol-induced neuronal death in mice.

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Lamarche, Frederic; Carcenac, Carole; Gonthier, Brigitte; Cottet-Rousselle, Cecile; Chauvin, Christiane; Barret, Luc; Leverve, Xavier; Savasta, Marc; Fontaine, Eric

2013-01-18

Ethanol induces brain injury by a mechanism that remains partly unknown. Mitochondria play a key role in cell death processes, notably through the opening of the permeability transition pore (PTP). Here, we tested the effect of ethanol and PTP inhibitors on mitochondrial physiology and cell viability both in vitro and in vivo. Direct addition of ethanol up to 100 mM on isolated mouse brain mitochondria slightly decreased oxygen consumption but did not affect PTP regulation. In comparison, when isolated from ethanol-treated (two doses of 2 g/kg, 2 h apart) 7-day-old mouse pups, brain mitochondria displayed a transient decrease in oxygen consumption but no change in PTP regulation or H2O2 production. Conversely, exposure of primary cultured astrocytes and neurons to 20 mM ethanol for 3 days led to a transient PTP opening in astrocytes without affecting cell viability and to a permanent PTP opening in 10 to 20% neurons with the same percentage of cell death. Ethanol-treated mouse pups displayed a widespread caspase-3 activation in neurons but not in astrocytes and dramatic behavioral alterations. Interestingly, two different PTP inhibitors (namely, cyclosporin A and nortriptyline) prevented both ethanol-induced neuronal death in vivo and ethanol-induced behavioral modifications. We conclude that PTP opening is involved in ethanol-induced neurotoxicity in the mouse.

Sodium selenite/selenium nanoparticles (SeNPs) protect cardiomyoblasts and zebrafish embryos against ethanol induced oxidative stress.

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Kalishwaralal, Kalimuthu; Jeyabharathi, Subhaschandrabose; Sundar, Krishnan; Muthukumaran, Azhaguchamy

2015-10-01

Alcoholic cardiomyopathy is the damage caused to the heart muscles due to high level of alcohol consumption resulting in enlargement and inflammation of the heart. Selenium is an important trace element that is beneficial to human health. Selenium protects the cells by preventing the formation of free radicals in the body. In the present study, protein mediated synthesis of SeNPs was investigated. Two different sizes of SeNPs were synthesized using BSA and keratin. The synthesized SeNPs were characterized by scanning electron microscopy (SEM) with elemental composition analysis Energy Dispersive X-ray spectroscopy(EDX) and X-ray diffraction (XRD). This study demonstrates the in vitro and in vivo antioxidative effects of sodium selenite and SeNPs. Further selenium and SeNPs were evaluated for their ability to protect against 1% ethanol induced oxidative stress in H9C2 cell line. The selenium and SeNPs were found to reduce the 1% ethanol-induced oxidative damage through scavenging intracellular reactive oxygen species. The selenium and SeNPs could also prevent pericardial edema induced ethanol treatment and reduced apoptosis and cell death in zebrafish embryos. The results indicate that selenium and SeNPs could potentially be used as an additive in alcoholic beverage industry to control the cardiomyopathy. Copyright © 2015 Elsevier GmbH. All rights reserved.

Alpha 7 nicotinic acetylcholine receptor-mediated protection against ethanol-induced neurotoxicity.

Science.gov (United States)

de Fiebre, NancyEllen C; de Fiebre, Christopher M

2003-11-01

The alpha(7)-selective nicotinic partial agonist 3-[2,4-dimethoxybenzylidene]anabaseine (DMXB) was examined for its ability to modulate ethanol-induced neurotoxicity in primary cultures of rat neurons. Primary cultures of hippocampal neurons were established from Long-Evans, embryonic day (E)-18 rat fetuses and maintained for 7 days. Ethanol (0-150 mM), DMXB (0-56 microM), or both were subsequently co-applied to cultures. Ethanol was added two additional times to the cultures to compensate for evaporation. After 5 days, neuronal viability was assessed with the MTT cell proliferation assay. Results demonstrated that ethanol reduces neuronal viability in a concentration-dependent fashion and that DMXB protects against this ethanol-induced neurotoxicity, also in a concentration-dependent fashion. These results support the suggestion that nicotinic partial agonists may be useful in treating binge drinking-induced neurotoxicity and may provide clues as to why heavy drinkers are usually smokers.

Alterations in ethanol-induced behaviors and consumption in knock-in mice expressing ethanol-resistant NMDA receptors.

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Carolina R den Hartog

Full Text Available Ethanol's action on the brain likely reflects altered function of key ion channels such as glutamatergic N-methyl-D-aspartate receptors (NMDARs. In this study, we determined how expression of a mutant GluN1 subunit (F639A that reduces ethanol inhibition of NMDARs affects ethanol-induced behaviors in mice. Mice homozygous for the F639A allele died prematurely while heterozygous knock-in mice grew and bred normally. Ethanol (44 mM; ∼0.2 g/dl significantly inhibited NMDA-mediated EPSCs in wild-type mice but had little effect on responses in knock-in mice. Knock-in mice had normal expression of GluN1 and GluN2B protein across different brain regions and a small reduction in levels of GluN2A in medial prefrontal cortex. Ethanol (0.75-2.0 g/kg; i.p. increased locomotor activity in wild-type mice but had no effect on knock-in mice while MK-801 enhanced activity to the same extent in both groups. Ethanol (2.0 g/kg reduced rotarod performance equally in both groups but knock-in mice recovered faster following a higher dose (2.5 g/kg. In the elevated zero maze, knock-in mice had a blunted anxiolytic response to ethanol (1.25 g/kg as compared to wild-type animals. No differences were noted between wild-type and knock-in mice for ethanol-induced loss of righting reflex, sleep time, hypothermia or ethanol metabolism. Knock-in mice consumed less ethanol than wild-type mice during daily limited-access sessions but drank more in an intermittent 24 h access paradigm with no change in taste reactivity or conditioned taste aversion. Overall, these data support the hypothesis that NMDA receptors are important in regulating a specific constellation of effects following exposure to ethanol.

Alterations in ethanol-induced behaviors and consumption in knock-in mice expressing ethanol-resistant NMDA receptors.

Science.gov (United States)

den Hartog, Carolina R; Beckley, Jacob T; Smothers, Thetford C; Lench, Daniel H; Holseberg, Zack L; Fedarovich, Hleb; Gilstrap, Meghin J; Homanics, Gregg E; Woodward, John J

2013-01-01

Ethanol's action on the brain likely reflects altered function of key ion channels such as glutamatergic N-methyl-D-aspartate receptors (NMDARs). In this study, we determined how expression of a mutant GluN1 subunit (F639A) that reduces ethanol inhibition of NMDARs affects ethanol-induced behaviors in mice. Mice homozygous for the F639A allele died prematurely while heterozygous knock-in mice grew and bred normally. Ethanol (44 mM; ∼0.2 g/dl) significantly inhibited NMDA-mediated EPSCs in wild-type mice but had little effect on responses in knock-in mice. Knock-in mice had normal expression of GluN1 and GluN2B protein across different brain regions and a small reduction in levels of GluN2A in medial prefrontal cortex. Ethanol (0.75-2.0 g/kg; i.p.) increased locomotor activity in wild-type mice but had no effect on knock-in mice while MK-801 enhanced activity to the same extent in both groups. Ethanol (2.0 g/kg) reduced rotarod performance equally in both groups but knock-in mice recovered faster following a higher dose (2.5 g/kg). In the elevated zero maze, knock-in mice had a blunted anxiolytic response to ethanol (1.25 g/kg) as compared to wild-type animals. No differences were noted between wild-type and knock-in mice for ethanol-induced loss of righting reflex, sleep time, hypothermia or ethanol metabolism. Knock-in mice consumed less ethanol than wild-type mice during daily limited-access sessions but drank more in an intermittent 24 h access paradigm with no change in taste reactivity or conditioned taste aversion. Overall, these data support the hypothesis that NMDA receptors are important in regulating a specific constellation of effects following exposure to ethanol.

Is there a role for leukotrienes as mediators of ethanol-induced gastric mucosal damage?

International Nuclear Information System (INIS)

Wallace, J.L.; Beck, P.L.; Morris, G.P.

1988-01-01

The role of leukotriene (LT) C 4 as a mediator of ethanol-induced gastric mucosal damage was investigated. Rats were pretreated with a number of compounds, including inhibitors of leukotriene biosynthesis and agents that have previously been shown to reduce ethanol-induced damage prior to oral administration of absolute ethanol. Ethanol administration resulted in a fourfold increase in LTC 4 synthesis. LTC 4 synthesis could be reduced significantly by pretreatment with L651,392 or dexamethosone without altering the susceptibility of the gastric mucosa to ethanol-induced damage. Furthermore, changes in LBT 4 synthesis paralleled the changes in LTC 4 synthesis observed after ethanol administration. The effects of ethanol on gastric eicosanoid synthesis were further examined using an ex vivo gastric chamber preparation that allowed for application of ethanol to only one side of the stomach. These studies confirm that ethanol can stimulate gastric leukotriene synthesis independent of the production of hemorrhagic damage. Inhibition of LTC 4 synthesis does not confer protection to the mucosa, suggesting that LTC 4 does not play an important role in the etiology of ethanol-induced gastric damage

Gastroprotective, cytoprotective and antioxidant effects of Oleum cinnamomi on ethanol induced damage

OpenAIRE

Ozbayer, Cansu; Kurt, Hulyam; Ozdemir, Zeynep; Tuncel, Tunc; Moheb Saadat, Selva; Burukoglu, Dilek; Senturk, Hakan; Degirmenci, Irfan; Gunes, Hasan Veysi

2013-01-01

Peptic ulcer disease is a gastrointestinal disorder defined by mucosal damage and free oxygen radicals associated with peptic ulcer and gastritis. Cinnamon is a traditional herb used for many diseases and it has also effects as an antioxidant, anti-inflammatory, antispasmodic and anti-ulcerative. Our research is based on oxidative stress and effects of Oleum cinnamomi on stomach, liver and kidney disorders induced by ethanol. In our experiment, 2–3 month old male Sprague–Dawley rats were used...

Blockade of store-operated calcium entry alleviates ethanol-induced hepatotoxicity via inhibiting apoptosis

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Cui, Ruibing [Department of Hepatology and Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong Province 250012 (China); Yan, Lihui [Shandong Normal University, Jinan, Shandong Province 250012 (China); Luo, Zheng; Guo, Xiaolan [Department of Hepatology and Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong Province 250012 (China); Yan, Ming, E-mail: ymylh@163.com [Department of Hepatology and Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong Province 250012 (China)

2015-08-15

Extracellular Ca{sup 2+} influx has been suggested to play a role in ethanol-induced hepatocyte apoptosis and necrosis. Previous studies indicated that store-operated Ca{sup 2+} entry (SOCE) was involved in liver injury induced by ethanol in HepG2 cells. However, the mechanisms underlying liver injury caused by SOCE remain unclear. We aimed to investigate the effects and mechanism of SOCE inhibition on liver injury induced by ethanol in BRL cells and Sprague–Dawley rats. Our data demonstrated that ethanol (0–400 mM) dose-dependently increased hepatocyte injury and 100 mM ethanol significantly upregulated the mRNA and protein expression of SOC for at least 72 h in BRL cells. Blockade of SOCE by pharmacological inhibitors and sh-RNA knockdown of STIM1 and Orai1 attenuated intracellular Ca{sup 2+} overload, restored the mitochondrial membrane potential (MMP), decreased cytochrome C release and inhibited ethanol-induced apoptosis. STIM1 and Orai1 expression was greater in ethanol-treated than control rats, and the SOCE inhibitor corosolic acid ameliorated the histopathological findings and alanine transaminase and aspartate transaminase activity as well as decreased cytochrome C release and inhibited alcohol-induced cell apoptosis. These findings suggest that SOCE blockade could alleviate alcohol-induced hepatotoxicity via inhibiting apoptosis. SOCE might be a useful therapeutic target in alcoholic liver diseases. - Highlights: • Blockade of SOCE alleviated overload of Ca{sup 2+} and hepatotoxicity after ethanol application. • Blockade of SOCE inhibited mitochondrial apoptosis after ethanol application. • SOCE might be a useful therapeutic target in alcoholic liver diseases.

Subacute ethanol consumption reverses p-xylene-induced decreases in axonal transport

Energy Technology Data Exchange (ETDEWEB)

Padilla, S.; Lyerly, D.L.; Pope, C.N.

1992-01-01

Organic solvants, as a class, have been implicated as neurotoxic agents in humans and laboratory animals. The study was designed to assess the interaction between subacute ingestion of moderate levels of ethanol and the p-xylene-induced decreases in protein and glycoprotein synthesis and axonal transport in the rat optic system. The results indicated that animals maintained on 10% ethanol as a drinking liquid show less p-xylene-induced neurotoxicity than animals receiving no ethanol supplement.

Autophagy Protects against CYP2E1/Chronic Ethanol-Induced Hepatotoxicity

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Yongke Lu

2015-10-01

Full Text Available Autophagy is an intracellular pathway by which lysosomes degrade and recycle long-lived proteins and cellular organelles. The effects of ethanol on autophagy are complex but recent studies have shown that autophagy serves a protective function against ethanol-induced liver injury. Autophagy was found to also be protective against CYP2E1-dependent toxicity in vitro in HepG2 cells which express CYP2E1 and in vivo in an acute alcohol/CYPE1-dependent liver injury model. The goal of the current report was to extend the previous in vitro and acute in vivo experiments to a chronic ethanol model to evaluate whether autophagy is also protective against CYP2E1-dependent liver injury in a chronic ethanol-fed mouse model. Wild type (WT, CYP2E1 knockout (KO or CYP2E1 humanized transgenic knockin (KI, mice were fed an ethanol liquid diet or control dextrose diet for four weeks. In the last week, some mice received either saline or 3-methyladenine (3-MA, an inhibitor of autophagy, or rapamycin, which stimulates autophagy. Inhibition of autophagy by 3-MA potentiated the ethanol-induced increases in serum transaminase and triglyceride levels in the WT and KI mice but not KO mice, while rapamycin prevented the ethanol liver injury. Treatment with 3-MA enhanced the ethanol-induced fat accumulation in WT mice and caused necrosis in the KI mice; little or no effect was found in the ethanol-fed KO mice or any of the dextrose-fed mice. 3-MA treatment further lowered the ethanol-decrease in hepatic GSH levels and further increased formation of TBARS in WT and KI mice, whereas rapamycin blunted these effects of ethanol. Neither 3-MA nor rapamycin treatment affected CYP2E1 catalytic activity or content or the induction CYP2E1 by ethanol. The 3-MA treatment decreased levels of Beclin-1 and Atg 7 but increased levels of p62 in the ethanol-fed WT and KI mice whereas rapamycin had the opposite effects, validating inhibition and stimulation of autophagy, respectively. These

Ethanol activation of protein kinase A regulates GABA-A receptor subunit expression in the cerebral cortex and contributes to ethanol-induced hypnosis

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Sandeep eKumar

2012-04-01

Full Text Available Protein kinases are implicated in neuronal cell functions such as modulation of ion channel function, trafficking and synaptic excitability. Both protein kinase C (PKC and A (PKA are involved in regulation of γ-aminobutyric acid type A (GABA-A receptors through phosphorylation. However, the role of PKA in regulating GABA-A receptors following acute ethanol exposure is not known. The present study investigated the role of PKA in ethanol effects on GABA-A receptor α1 subunit expression in the P2 synaptosomal fraction of the rat cerebral cortex. Additionally, GABA-related behaviors were also examined. Rats were administered ethanol (2.0 – 3.5 g/kg or saline and PKC, PKA and GABA-A receptor α1 subunit levels were measured by Western blot analysis. Ethanol (3.5 g/kg transiently increased GABA-A receptor α1 subunit expression and PKA RIIβ subunit expression at similar time points whereas PKA RIIα was increased at later time points. In contrast, PKC isoform expression remained unchanged. Notably, the moderate ethanol dose (2.0g/kg had no effect on GABA-A α1 subunit levels although PKA RIIα and RIIβ were increased at 10 and 60 minutes, when PKC isozymes are also known to be elevated. To determine if PKA activation was responsible for the ethanol-induced elevation of GABA-A α1 subunits, the PKA antagonist H89 was administered to rats prior to ethanol exposure. H89 administration prevented ethanol-induced increases in GABA-A receptor α1 subunit expression. Moreover, increasing PKA activity intracerebroventricularly with Sp-cAMP prior to a hypnotic dose of ethanol increased ethanol-induced loss of righting reflex duration. This effect appears to be mediated in part by GABA-A receptors as increasing PKA activity also increased the duration of muscimol-induced loss of righting reflex. Overall these data suggest that PKA mediates ethanol-induced GABA-A receptor expression and contributes to ethanol behavioral effects involving GABA-A receptors.

Effect of topical vitamin E on ethanol-induced corneal epithelial apoptosis.

Science.gov (United States)

Bilgihan, Kamil; Konuk, Onur; Hondur, Ahmet; Akyürek, Nalan; Ozogul, Candan; Hasanreisoglu, Berati

2005-01-01

Ethanol is used to loosen the corneal epithelium before photoablation in laser subepithelial keratomileusis (LASEK). In this study, the apoptotic index of corneal epithelium after ethanol exposure and the effects of topical vitamin E were evaluated. The study was performed on 28 rabbit eyes in four groups. Group 1 comprised the controls. In group 2, 20% ethanol was applied topically for 20 seconds. In group 3, topical vitamin E was applied following 20% ethanol application. In group 4, only topical vitamin E was applied. Apoptosis was evaluated with TUNEL assay and transmission electron microscopy. Epithelial apoptosis was detected in all specimens in group 2. No apoptosis was detected in other groups except for one eye in group 1. The apoptotic index in group 2 was statistically higher than other groups (P < .001).

Mutation of the inhibitory ethanol site in GABAA ρ1 receptors promotes tolerance to ethanol-induced motor incoordination.

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Blednov, Yuri A; Borghese, Cecilia M; Ruiz, Carlos I; Cullins, Madeline A; Da Costa, Adriana; Osterndorff-Kahanek, Elizabeth A; Homanics, Gregg E; Harris, R Adron

2017-09-01

Genes encoding the ρ1/2 subunits of GABA A receptors have been associated with alcohol (ethanol) dependence in humans, and ρ1 was also shown to regulate some of the behavioral effects of ethanol in animal models. Ethanol inhibits GABA-mediated responses in wild-type (WT) ρ1, but not ρ1(T6'Y) mutant receptors expressed in Xenopus laevis oocytes, indicating the presence of an inhibitory site for ethanol in the second transmembrane helix. In this study, we found that ρ1(T6'Y) receptors expressed in oocytes display overall normal responses to GABA, the endogenous GABA modulator (zinc), and partial agonists (β-alanine and taurine). We generated ρ1 (T6'Y) knockin (KI) mice using CRISPR/Cas9 to test the behavioral importance of the inhibitory actions of ethanol on this receptor. Both ρ1 KI and knockout (KO) mice showed faster recovery from acute ethanol-induced motor incoordination compared to WT mice. Both KI and KO mutant strains also showed increased tolerance to motor impairment produced by ethanol. The KI mice did not differ from WT mice in other behavioral actions, including ethanol intake and preference, conditioned taste aversion to ethanol, and duration of ethanol-induced loss of righting reflex. WT and KI mice did not differ in levels of ρ1 or ρ2 mRNA in cerebellum or in ethanol clearance. Our findings indicate that the inhibitory site for ethanol in GABA A ρ1 receptors regulates acute functional tolerance to moderate ethanol intoxication. We note that low sensitivity to alcohol intoxication has been linked to risk for development of alcohol dependence in humans. Copyright © 2017 Elsevier Ltd. All rights reserved.

Ethanol-induced conditioned taste avoidance: reward or aversion?

Science.gov (United States)

Liu, Chuang; Showalter, John; Grigson, Patricia Sue

2009-03-01

Rats avoid intake of a palatable taste cue when paired with all drugs of abuse tested. Evidence suggests that, at least for morphine and cocaine, rats avoid the taste cue because they are anticipating the rewarding properties of the drug. Thus, the suppressive effects of a rewarding sucrose solution and cocaine, but not those of the putatively aversive agent, lithium chloride (LiCl), are exaggerated in drug-sensitive Lewis rats. Likewise, the suppressive effects of sucrose and morphine, but not those of LiCl, are eliminated by bilateral lesions of the gustatory thalamus. Unlike morphine and cocaine, it is less clear whether rewarding or aversive drug properties are responsible for ethanol-induced suppression of intake of a taste cue. The present set of studies tests whether, like cocaine, ethanol-induced suppression of intake of a taste cue also is greater in the drug-sensitive Lewis rats and whether the suppressive effects of the drug are prevented by bilateral lesions of the taste thalamus. In Experiment 1, fluid-deprived Lewis and Fischer rats were given 5-minute access to 0.15% saccharin and then injected with saline or a range of doses of ethanol (0.5, 0.75, 1.0, or 1.5 g/kg). There was a total of 6 such pairings. In Experiments 2 and 3, Sprague-Dawley rats received bilateral electrophysiologically guided lesions of the gustatory thalamus. After recovery, suppression of intake of the saccharin cue was evaluated following repeated daily pairings with either a high (1.5 g/kg) or a low (0.75 g/kg) dose of ethanol. Ethanol-induced suppression of intake of the saccharin conditioned stimulus (CS) did not differ between the drug-sensitive Lewis rats relative to the less-sensitive Fischer rats. Lesions of the taste thalamus, however, prevented the suppressive effect of the 0.75 g/kg dose of the drug, but had no impact on the suppressive effect of the 1.5 g/kg dose of ethanol. The results suggest that the suppressive effects of ethanol on CS intake are mediated by both

The turmeric protective properties at ethanol-induced behavioral disorders.

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Goldina I.A.

2017-03-01

Full Text Available The aim of the study was to determine the effect of mechanically modified turmeric extract on the parameters of orienting-exploratory behavior in mice with chronic ethanol consumption. Material and methods. Mice behavior was assessed in the "open field" test. In the both control groups the animals received water or 10% ethanol solution; in the test group — turmeric extract in 10% ethanol solution. Amount of blood mononuclear cells, thymocytes, and splenocytes were estimated. Results. Analysis of the behavioral parameters in animals after chronic exposure to ethanol showed suppression of motor and exploratory components of the behavior. In mice that received both ethanol and turmeric extract recorded behavior parameters were significantly higher than in the group of animals who received ethanol only. It was shown that the turmeric extract enhances the amount of blood immune cells. Conclusion. Mechanically modified turmeric extract possesses protective properties against ethanol-induced behavioral disorders.

Lipids and Oxidative Stress Associated with Ethanol-Induced Neurological Damage

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José A. Hernández

2016-01-01

Full Text Available The excessive intake of alcohol is a serious public health problem, especially given the severe damage provoked by chronic or prenatal exposure to alcohol that affects many physiological processes, such as memory, motor function, and cognitive abilities. This damage is related to the ethanol oxidation in the brain. The metabolism of ethanol to acetaldehyde and then to acetate is associated with the production of reactive oxygen species that accentuate the oxidative state of cells. This metabolism of ethanol can induce the oxidation of the fatty acids in phospholipids, and the bioactive aldehydes produced are known to be associated with neurotoxicity and neurodegeneration. As such, here we will review the role of lipids in the neuronal damage induced by ethanol-related oxidative stress and the role that lipids play in the related compensatory or defense mechanisms.

Environmental enrichment reduces chronic psychosocial stress-induced anxiety and ethanol-related behaviors in mice.

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Bahi, Amine

2017-07-03

Previous research from our laboratory has shown that exposure to chronic psychosocial stress increased voluntary ethanol consumption and preference as well as acquisition of ethanol-induced conditioned place preference (CPP) in mice. This study was done to determine whether an enriched environment could have "curative" effects on chronic psychosocial stress-induced ethanol intake and CPP. For this purpose, experimental mice "intruders" were exposed to the chronic subordinate colony (CSC) housing for 19 consecutive days in the presence of an aggressive "resident" mouse. At the end of that period, mice were tested for their anxiety-like behavior using the elevated plus maze (EPM) test then housed in a standard or enriched environment (SE or EE respectively). Anxiety and ethanol-related behaviors were investigated using the open field (OF) test, a standard two-bottle choice drinking paradigm, and the CPP procedure. As expected, CSC exposure increased anxiety-like behavior and reduced weight gain as compared to single housed colony (SHC) controls. In addition, CSC exposure increased voluntary ethanol intake and ethanol-CPP. Interestingly, we found that EE significantly and consistently reduced anxiety and ethanol consumption and preference. However, neither tastants' (saccharin and quinine) intake nor blood ethanol metabolism were affected by EE. Finally, and most importantly, EE reduced the acquisition of CPP induced by 1.5g/kg ethanol. Taken together, these results support the hypothesis that EE can reduce voluntary ethanol intake and ethanol-induced conditioned reward and seems to be one of the strategies to reduce the behavioral deficits and the risk of anxiety-induced alcohol abuse. Copyright © 2017 Elsevier Inc. All rights reserved.

Curcuma aromatica Water Extract Attenuates Ethanol-Induced Gastritis via Enhancement of Antioxidant Status

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Woo-Young Jeon

2015-01-01

Full Text Available Curcuma aromatica is an herbal medicine and traditionally used for the treatment of various diseases in Asia. We investigated the effects of C. aromatica water extract (CAW in the stomach of rats with ethanol-induced gastritis. Gastritis was induced in rats by intragastric administration of 5 mL/kg body weight of absolute ethanol. The CAW groups were given 250 or 500 mg of extract/kg 2 h before administration of ethanol, respectively. To determine the antioxidant effects of CAW, we determined the level of lipid peroxidation, the level of reduced glutathione (GSH, the activities of catalase, degree of inflammation, and mucus production in the stomach. CAW reduced ethanol-induced inflammation and loss of epithelial cells and increased the mucus production in the stomach. CAW reduced the increase in lipid peroxidation associated with ethanol-induced gastritis (250 and 500 mg/kg, p<0.01, resp. and increased mucosal GSH content (500 mg/kg, p<0.01 and the activity of catalase (250 and 500 mg/kg, p<0.01, resp.. CAW increased the production of prostaglandin E2. These findings suggest that CAW protects against ethanol-induced gastric mucosa injury by increasing antioxidant status. We suggest that CAW could be developed for the treatment of gastritis induced by alcohol.

Ethanol exposure induces the cancer-associated fibroblast phenotype and lethal tumor metabolism

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Sanchez-Alvarez, Rosa; Martinez-Outschoorn, Ubaldo E.; Lin, Zhao; Lamb, Rebecca; Hulit, James; Howell, Anthony; Sotgia, Federica; Rubin, Emanuel; Lisanti, Michael P.

2013-01-01

Little is known about how alcohol consumption promotes the onset of human breast cancer(s). One hypothesis is that ethanol induces metabolic changes in the tumor microenvironment, which then enhances epithelial tumor growth. To experimentally test this hypothesis, we used a co-culture system consisting of human breast cancer cells (MCF7) and hTERT-immortalized fibroblasts. Here, we show that ethanol treatment (100 mM) promotes ROS production and oxidative stress in cancer-associated fibroblasts, which is sufficient to induce myofibroblastic differentiation. Oxidative stress in stromal fibroblasts also results in the onset of autophagy/mitophagy, driving the induction of ketone body production in the tumor microenvironment. Interestingly, ethanol has just the opposite effect in epithelial cancer cells, where it confers autophagy resistance, elevates mitochondrial biogenesis and induces key enzymes associated with ketone re-utilization (ACAT1/OXCT1). During co-culture, ethanol treatment also converts MCF7 cells from an ER(+) to an ER(-) status, which is thought to be associated with “stemness,” more aggressive behavior and a worse prognosis. Thus, ethanol treatment induces ketone production in cancer-associated fibroblasts and ketone re-utilization in epithelial cancer cells, fueling tumor cell growth via oxidative mitochondrial metabolism (OXPHOS). This “two-compartment” metabolic model is consistent with previous historical observations that ethanol is first converted to acetaldehyde (which induces oxidative stress) and then ultimately to acetyl-CoA (a high-energy mitochondrial fuel), or can be used to synthesize ketone bodies. As such, our results provide a novel mechanism by which alcohol consumption could metabolically convert “low-risk” breast cancer patients to “high-risk” status, explaining tumor recurrence or disease progression. Hence, our findings have clear implications for both breast cancer prevention and therapy. Remarkably, our results

Involvement of brain catalase activity in the acquisition of ethanol-induced conditioned place preference.

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Font, Laura; Miquel, Marta; Aragon, Carlos M G

2008-03-18

It has been suggested that some of the behavioral effects produced by ethanol are mediated by its first metabolite, acetaldehyde. The present research addressed the hypothesis that catalase-dependent metabolism of ethanol to acetaldehyde in the brain is an important step in the production of ethanol-related affective properties. Firstly, we investigated the contribution of brain catalase in the acquisition of ethanol-induced conditioned place preference (CPP). Secondly, the specificity of the catalase inhibitor 3-amino-1,2,4-triazole (AT) was evaluated with morphine- and cocaine-induced CPP. Finally, to investigate the role of catalase in the process of relapse to ethanol seeking caused by re-exposure to ethanol, after an initial conditioning and extinction, mice were primed with saline and ethanol or AT and ethanol and tested for reinstatement of CPP. Conditioned place preference was blocked in animals treated with AT and ethanol. Morphine and cocaine CPP were unaffected by AT treatment. However, the reinstatement of place preference was not modified by catalase inhibition. Taken together, the results of the present study indicate that the brain catalase-H(2)O(2) system contributes to the acquisition of affective-dependent learning induced by ethanol, and support the involvement of centrally-formed acetaldehyde in the formation of positive affective memories produced by ethanol.

Excitation of lateral habenula neurons as a neural mechanism underlying ethanol-induced conditioned taste aversion.

Science.gov (United States)

Tandon, Shashank; Keefe, Kristen A; Taha, Sharif A

2017-02-15

The lateral habenula (LHb) has been implicated in regulation of drug-seeking behaviours through aversion-mediated learning. In this study, we recorded neuronal activity in the LHb of rats during an operant task before and after ethanol-induced conditioned taste aversion (CTA) to saccharin. Ethanol-induced CTA caused significantly higher baseline firing rates in LHb neurons, as well as elevated firing rates in response to cue presentation, lever press and saccharin taste. In a separate cohort of rats, we found that bilateral LHb lesions blocked ethanol-induced CTA. Our results strongly suggest that excitation of LHb neurons is required for ethanol-induced CTA, and point towards a mechanism through which LHb firing may regulate voluntary ethanol consumption. Ethanol, like other drugs of abuse, has both rewarding and aversive properties. Previous work suggests that sensitivity to ethanol's aversive effects negatively modulates voluntary alcohol intake and thus may be important in vulnerability to developing alcohol use disorders. We previously found that rats with lesions of the lateral habenula (LHb), which is implicated in aversion-mediated learning, show accelerated escalation of voluntary ethanol consumption. To understand neural encoding in the LHb contributing to ethanol-induced aversion, we recorded neural firing in the LHb of freely behaving, water-deprived rats before and after an ethanol-induced (1.5 g kg -1 20% ethanol, i.p.) conditioned taste aversion (CTA) to saccharin taste. Ethanol-induced CTA strongly decreased motivation for saccharin in an operant task to obtain the tastant. Comparison of LHb neural firing before and after CTA induction revealed four main differences in firing properties. First, baseline firing after CTA induction was significantly higher. Second, firing evoked by cues signalling saccharin availability shifted from a pattern of primarily inhibition before CTA to primarily excitation after CTA induction. Third, CTA induction reduced

Effect of methanolic extract of Hibiscus sabdariffa in ethanol-induced ...

African Journals Online (AJOL)

The objective of this study was to evaluate the activity of Hibiscus sabdariffa on the liver of rats following repeated administration of ethanol. Hepatotoxicity was induced on the rats using ethanol and the levels of serum enzymes such as serum glutamic pyruvic transaminase (SGPT), serum glutamic oxaloacetic transaminase ...

Hepatoprotective effects of pecan nut shells on ethanol-induced liver damage.

Science.gov (United States)

Müller, Liz Girardi; Pase, Camila Simonetti; Reckziegel, Patrícia; Barcelos, Raquel C S; Boufleur, Nardeli; Prado, Ana Cristina P; Fett, Roseane; Block, Jane Mara; Pavanato, Maria Amália; Bauermann, Liliane F; da Rocha, João Batista Teixeira; Burger, Marilise Escobar

2013-01-01

The hepatoprotective activity of the aqueous extract of the shells of pecan nut was investigated against ethanol-induced liver damage. This by-product of the food industry is popularly used to treat toxicological diseases. We evaluated the phytochemical properties of pecan shell aqueous extract (AE) and its in vitro and ex vivo antioxidant activity. The AE was found to have a high content of total polyphenols (192.4±1.9 mg GAE/g), condensed tannins (58.4±2.2 mg CE/g), and antioxidant capacity, and it inhibited Fe(2+)-induced lipid peroxidation (LP) in vitro. Rats chronically treated with ethanol (Et) had increased plasmatic transaminases (ALT, AST) and gamma glutamyl transpeptidase (GGT) levels (96%, 59.13% and 465.9%, respectively), which were effectively prevented (87; 41 and 383%) by the extract (1:40, w/v). In liver, ethanol consumption increased the LP (121%) and decreased such antioxidant defenses as glutathione (GSH) (33%) and superoxide dismutase (SOD) (47%) levels, causing genotoxicity in erythrocytes. Treatment with pecan shell AE prevented the development of LP (43%), GSH and SOD depletion (33% and 109%, respectively) and ethanol-induced erythrocyte genotoxicity. Catalase activity in the liver was unchanged by ethanol but was increased by the extract (47% and 73% in AE and AE+Et, respectively). Therefore, pecan shells may be an economic agent to treat liver diseases related to ethanol consumption. Copyright © 2011 Elsevier GmbH. All rights reserved.

Role of Unsaturated Lipid and Ergosterol in Ethanol Tolerance of Model Yeast Biomembranes

KAUST Repository

Vanegas, Juan M.

2012-02-07

We present a combined atomic force microscopy and fluorescence microscopy study of the behavior of a ternary supported lipid bilayer system containing a saturated lipid (DPPC), an unsaturated lipid (DOPC), and ergosterol in the presence of high ethanol (20 vol %). We find that the fluorescent probe Texas Red DHPE preferentially partitions into the ethanol-induced interdigitated phase, which allows the use of fluorescence imaging to investigate the phase behavior of the system. Atomic force microscopy and fluorescence images of samples with the same lipid mixture show good agreement in sample morphology and area fractions of the observed phases. Using area fractions obtained from fluorescence images over a broad range of compositions, we constructed a phase diagram of the DPPC/DOPC/ergosterol system at 20 vol % ethanol. The phase diagram clearly shows that increasing unsaturated lipid and/or ergosterol protects the membrane by preventing the formation of the interdigitated phase. This result supports the hypothesis that yeast cells increase ergosterol and unsaturated lipid content to prevent interdigitation and maintain an optimal membrane thickness as ethanol concentration increases during anaerobic fermentations. Changes in plasma membrane composition provide an important survival factor for yeast cells to deter ethanol toxicity.

Role of Unsaturated Lipid and Ergosterol in Ethanol Tolerance of Model Yeast Biomembranes

KAUST Repository

Vanegas, Juan  M.; Contreras, Maria F.; Faller, Roland; Longo, Marjorie  L.

2012-01-01

We present a combined atomic force microscopy and fluorescence microscopy study of the behavior of a ternary supported lipid bilayer system containing a saturated lipid (DPPC), an unsaturated lipid (DOPC), and ergosterol in the presence of high ethanol (20 vol %). We find that the fluorescent probe Texas Red DHPE preferentially partitions into the ethanol-induced interdigitated phase, which allows the use of fluorescence imaging to investigate the phase behavior of the system. Atomic force microscopy and fluorescence images of samples with the same lipid mixture show good agreement in sample morphology and area fractions of the observed phases. Using area fractions obtained from fluorescence images over a broad range of compositions, we constructed a phase diagram of the DPPC/DOPC/ergosterol system at 20 vol % ethanol. The phase diagram clearly shows that increasing unsaturated lipid and/or ergosterol protects the membrane by preventing the formation of the interdigitated phase. This result supports the hypothesis that yeast cells increase ergosterol and unsaturated lipid content to prevent interdigitation and maintain an optimal membrane thickness as ethanol concentration increases during anaerobic fermentations. Changes in plasma membrane composition provide an important survival factor for yeast cells to deter ethanol toxicity.

Ethanol induces rotational behavior in 6-hydroxydopamine lesioned mice

Energy Technology Data Exchange (ETDEWEB)

Silverman, P.B.

1987-03-09

Mice with unilateal striatal lesions created by 6-hydroxydopamine (6HDA) injection were screened for rotational (circling) behavior in response to injection of amphetamine and apomorphine. Those that rotated ipsilaterally in response to amphetamine and contralaterally in response to apomorphine were subsequently challenged with 1 to 3 g/kg (i.p.) ethanol. Surprisingly, ethanol induced dose related contralateral (apomorphine-like) rotation which, despite gross intoxication, was quite marked in most animals. No significant correlation was found between the number of turns made following ethanol and made after apomorphine or amphetamine. 14 references, 2 figures, 1 table.

Study of ethanol-induced Golgi disorganization reveals the potential mechanism of alcohol-impaired N-glycosylation

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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

Sex differences in the effects of ethanol pre-exposure during adolescence on ethanol-induced conditioned taste aversion in adult rats.

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Sherrill, Luke K; Berthold, Claire; Koss, Wendy A; Juraska, Janice M; Gulley, Joshua M

2011-11-20

Alcohol use, which typically begins during adolescence and differs between males and females, is influenced by both the rewarding and aversive properties of the drug. One way adolescent alcohol use may modulate later consumption is by reducing alcohol's aversive properties. Here, we used a conditioned taste aversion (CTA) paradigm to determine if pre-exposure to alcohol (ethanol) during adolescence would attenuate ethanol-induced CTA assessed in adulthood in a sex-dependent manner. Male and female Long-Evans rats were given intraperitoneal (i.p.) injections of saline or 3.0g/kg ethanol in a binge-like pattern during postnatal days (PD) 35-45. In adulthood (>PD 100), rats were given access to 0.1% saccharin, followed by saline or ethanol (1.0 or 1.5g/kg, i.p.), over four conditioning sessions. We found sex differences in ethanol-induced CTA, with males developing a more robust aversion earlier in conditioning. Sex differences in the effects of pre-exposure were also evident: males, but not females, showed an attenuated CTA in adulthood following ethanol pre-exposure, which occurred approximately nine weeks earlier. Taken together, these findings indicate that males are more sensitive to the aversive properties of ethanol than females. In addition, the ability of pre-exposure to the ethanol US to attenuate CTA is enhanced in males compared to females. Copyright © 2011 Elsevier B.V. All rights reserved.

Deficient PKR in RAX/PKR Association Ameliorates Ethanol-Induced Neurotoxicity in the Developing Cerebellum.

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Li, Hui; Chen, Jian; Qi, Yuanlin; Dai, Lu; Zhang, Mingfang; Frank, Jacqueline A; Handshoe, Jonathan W; Cui, Jiajun; Xu, Wenhua; Chen, Gang

2015-08-01

Ethanol-induced neuronal loss is closely related to the pathogenesis of fetal alcohol spectrum disorders. The cerebellum is one of the brain areas that are most sensitive to ethanol. The mechanism underlying ethanol neurotoxicity remains unclear. Our previous in vitro studies have shown that the double-stranded RNA (dsRNA)-activated protein kinase (PKR) regulates neuronal apoptosis upon ethanol exposure and ethanol activates PKR through association with its intracellular activator RAX. However, the role of PKR and its interaction with RAX in vivo have not been investigated. In the current study, by utilizing N-PKR-/- mice, C57BL/6J mice with a deficient RAX-binding domain in PKR, we determined the critical role of RAX/PKR association in PKR-regulated ethanol neurotoxicity in the developing cerebellum. Our data indicate that while N-PKR-/- mice have a similar BAC profile as wild-type mice, ethanol induces less brain/body mass reduction as well as cerebellar neuronal loss. In addition, ethanol promotes interleukin-1β (IL-1β) secretion, and IL-1β is a master cytokine regulating inflammatory response. Importantly, ethanol-promoted IL-1β secretion is inhibited in the developing cerebellum of N-PKR-/- mice. Thus, RAX/PKR interaction and PKR activation regulate ethanol neurotoxicity in the developing cerebellum, which may involve ethanol-induced neuroinflammation. Further, PKR could be a possible target for pharmacological intervention to prevent or treat fetal alcohol spectrum disorder (FASD).

The effect of ethanol on the γ radiation induced polymerization of styrene

International Nuclear Information System (INIS)

Zhang Xujia; Ha Hongfei; Wu Jilan

1990-01-01

The γ radiation induced polymerization of styrene in the presence of ethanol was studied at dose rate of 5 x 10 17 eV/ml min. The result showed that the radiation induced polymerization of styrene was sensitized by ethanol. The experimental results were in agreement with the theoretical calculation of WAS equation. The mechanism of sensitization was proposed as proton transfer reaction

Effect of curcumin on ethanol-induced stress on mononuclear cells.

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Rajakrishnan, V; Shiney, S J; Sudhakaran, P R; Menon, V P

2002-03-01

Blood cells in circulation are exposed to a wide variety of stress-causing agents, causing a number of changes including interactions with other cells and the extracellular matrix of the endothelial wall. In order to understand the role of curcumin, an antioxidant principle from Curcuma longa Linn., on blood mononuclear cells from rabbits given ethanol for 30 days and ethanol with curcumin, cells were isolated and an attachment assay was carried out. The monocytes from ethanol-treated rabbits showed a lesser attachment to collagen, the major component of the vessel wall subendothelium, and those from curcumin treated animals along with ethanol showed a higher affinity to collagen, causing an alteration in the attachment of monocyte to collagen due to ethanol-induced stress. Copyright 2002 John Wiley & Sons, Ltd.

miR-217 Regulates Ethanol-Induced Hepatic Inflammation by Disrupting Sirtuin 1–Lipin-1 Signaling

OpenAIRE

Yin, Huquan; Liang, Xiaomei; Jogasuria, Alvin; Davidson, Nicholas O.; You, Min

2015-01-01

Ethanol-mediated injury, combined with gut-derived lipopolysaccharide (LPS), provokes generation of proinflammatory cytokines in Kupffer cells, causing hepatic inflammation. Among the mediators of these effects, miR-217 aggravates ethanol-induced steatosis in hepatocytes. However, the role of miR-217 in ethanol-induced liver inflammation process is unknown. Here, we examined the role of miR-217 in the responses to ethanol, LPS, or a combination of ethanol and LPS in RAW 264.7 macrophages and ...

Prioritized expression of BTN2 of Saccharomyces cerevisiae under pronounced translation repression induced by severe ethanol stress

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Yukina Yamauchi

2016-08-01

Full Text Available Severe ethanol stress (>9% ethanol, v/v as well as glucose deprivation rapidly induces a pronounced repression of overall protein synthesis in budding yeast Saccharomyces cerevisiae. Therefore, transcriptional activation in yeast cells under severe ethanol stress does not always indicate the production of expected protein levels. Messenger RNAs of genes containing heat shock elements can be intensively translated under glucose deprivation, suggesting that some mRNAs are preferentially translated even under severe ethanol stress. In the present study, we tried to identify the mRNA that can be preferentially translated under severe ethanol stress. BTN2 encodes a v-SNARE binding protein, and its null mutant shows hypersensitivity to ethanol. We found that BTN2 mRNA was efficiently translated under severe ethanol stress but not under mild ethanol stress. Moreover, the increased Btn2 protein levels caused by severe ethanol stress were smoothly decreased with the elimination of ethanol stress. These findings suggested that severe ethanol stress extensively induced BTN2 expression. Further, the BTN2 promoter induced protein synthesis of non-native genes such as CUR1, GIC2, and YUR1 in the presence of high ethanol concentrations, indicating that this promoter overcame severe ethanol stress-induced translation repression. Thus, our findings provide an important clue about yeast response to severe ethanol stress and suggest that the BTN2 promoter can be used to improve the efficiency of ethanol production and stress tolerance of yeast cells by modifying gene expression in the presence of high ethanol concentration.

Ethanol enhances GABA-induced 36Cl-influx in primary spinal cord cultured neurons

International Nuclear Information System (INIS)

Ticku, M.K.; Lowrimore, P.; Lehoullier, P.

1986-01-01

Ethanol has a pharmacological profile similar to other centrally acting drugs, which facilitate GABAergic transmission. GABA is known to produce its effects by increasing the conductance to Cl- ions. In this study, we have examined the effect of ethanol on GABA-induced 36Cl-influx in primary spinal cord cultured neurons. GABA produces a concentration-dependent, and saturable effect on 36Cl-influx in these neurons. Ethanol potentiates the effect of GABA on 36Cl-influx in these neurons. GABA (20 microM) increased the 36Cl-influx by 75% over the basal value, and in the presence of 50 mM ethanol, the observed increase was 142%. Eadie-Hoffstee analysis of the saturation curves indicated that ethanol decreases the Km value of GABA (10.6 microM to 4.2 microM), and also increases the Vmax. Besides potentiating the effect of GABA, ethanol also appears to have a direct effect in the absence of added GABA. These results suggest that ethanol enhances GABA-induced 36Cl-influx and indicate a role of GABAergic system in the actions of ethanol. These results also support the behavioral and electrophysiological studies, which have implicated GABA systems in the actions of ethanol. The potential mechanism(s) and the role of direct effect of ethanol is not clear at this time, but is currently being investigated

Fibroblast growth factor 21 (FGF21 is robustly induced by ethanol and has a protective role in ethanol associated liver injury

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Bhavna N. Desai

2017-11-01

Conclusions: Acute or binge ethanol consumption significantly increases circulating FGF21 levels in both humans and mice. However, FGF21 does not play a role in acute ethanol clearance. In contrast, chronic ethanol consumption in the absence of FGF21 is associated with significant liver pathology alone or in combination with excess mortality, depending on the type of diet consumed with ethanol. This suggests that FGF21 protects against long term ethanol induced hepatic damage and may attenuate progression of alcoholic liver disease. Further study is required to assess the therapeutic potential of FGF21 in the treatment of alcoholic liver disease.

Antiulcerogenic benefits of herbal ingredients in ethanol-induced ...

African Journals Online (AJOL)

Antiulcerogenic benefits of herbal ingredients in ethanol-induced animal models. ... Although therapeutic approaches are widely available, preventive regimens are limited. Numerous studies have demonstrated that herbal ... gastric ulcer. Key words: Herbal Medicines, Gastric ulcer, Prevention, Animal models, Alcohol ...

Brain catalase activity inhibition as well as opioid receptor antagonism increases ethanol-induced HPA axis activation.

Science.gov (United States)

Pastor, Raúl; Sanchis-Segura, Carles; Aragon, Carlos M G

2004-12-01

Growing evidence indicates that brain catalase activity is involved in the psychopharmacological actions of ethanol. Recent data suggest that participation of this enzymatic system in some ethanol effects could be mediated by the endogenous opioid system. The present study assessed whether brain catalase has a role in ethanol-induced activation of the HPA axis, a neuroendocrine system modulated by the endogenous opioid neurotransmission. Swiss male mice received an intraperitoneal injection of the catalase inhibitor 3-amino-1,2,4-triazole (AT; 0-1 g/kg), and 0 to 20 hr after this administration, animals received an ethanol (0-4 g/kg; intraperitoneally) challenge. Thirty, 60, or 120 min after ethanol administration, plasma corticosterone levels were determined immunoenzymatically. In addition, we tested the effects of 45 mg/kg of cyanamide (another catalase inhibitor) and 0 to 2 mg/kg of naltrexone (nonselective opioid receptor antagonist) on ethanol-induced enhancement in plasma corticosterone values. The present study revealed that AT boosts ethanol-induced increase in plasma corticosterone levels in a dose- and time-dependent manner. However, it did not affect corticosterone values when measured after administration of saline, cocaine (4 mg/kg, intraperitoneally), or morphine (30 mg/kg, intraperitoneally). The catalase inhibitor cyanamide (45 mg/kg, intraperitoneally) also increased ethanol-related plasma corticosterone levels. These effects of AT and cyanamide on ethanol-induced corticosterone values were observed under treatment conditions that decreased significantly brain catalase activity. Indeed, a significant correlation between effects of catalase manipulations on both variables was found. Finally, we found that the administration of naltrexone enhanced the levels of plasma corticosterone after the administration of saline or ethanol. This study shows that the inhibition of brain catalase increases ethanol-induced plasma corticosterone levels. Results are

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

Science.gov (United States)

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.

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

Science.gov (United States)

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.

Carnosine supplementation protects rat brain tissue against ethanol-induced oxidative stress.

Science.gov (United States)

Ozel Turkcu, Ummuhani; Bilgihan, Ayşe; Biberoglu, Gursel; Mertoglu Caglar, Oznur

2010-06-01

Ethanol causes oxidative stress and tissue damage. The aim of this study was to investigate the effect of antioxidant carnosine on the oxidative stress induced by ethanol in the rat brain tissue. Forty male rats were divided equally into four groups as control, carnosine (CAR), ethanol (EtOH), and ethanol plus carnosine (EtOH + CAR). Rats in the control group (n = 10) were injected intraperitoneally (i.p.) with 0.9% saline; EtOH group (n = 10) with 2 g/kg/day ethanol, CAR group (n = 10) received carnosine at a dose of 1 mg/kg/day and EtOH + CAR group (n = 10) received carnosine (orally) and ethanol (i.p.). All animals were sacrificed using ketamine and brain tissues were removed. Malondialdehyde (MDA), protein carbonyl (PCO) and tissue carnosine levels, and superoxide dismutase (SOD) activities were measured. Endogenous CAR levels in the rat brain tissue specimens were significantly increased in the CAR and EtOH groups when compared to the control animals. MDA and PCO levels in the EtOH group were significantly increased as compared to the other groups (P < 0.05). CAR treatment also decreased MDA levels in the CAR group as compared to the control group. Increased SOD activities were obtained in the EtOH + CAR group as compared to the control (P < 0.05). CAR levels in the rat brain were significantly increased in the CAR, EtOH and CAR + EtOH groups when compared to the control animals. These findings indicated that carnosine may appear as a protective agent against ethanol-induced brain damage.

The H2O2 scavenger ebselen decreases ethanol-induced locomotor stimulation in mice.

Science.gov (United States)

Ledesma, Juan Carlos; Font, Laura; Aragon, Carlos M G

2012-07-01

In the brain, the enzyme catalase by reacting with H(2)O(2) forms Compound I (catalase-H(2)O(2) system), which is the main system of central ethanol metabolism to acetaldehyde. Previous research has demonstrated that acetaldehyde derived from central-ethanol metabolism mediates some of the psychopharmacological effects produced by ethanol. Manipulations that modulate central catalase activity or sequester acetaldehyde after ethanol administration modify the stimulant effects induced by ethanol in mice. However, the role of H(2)O(2) in the behavioral effects caused by ethanol has not been clearly addressed. The present study investigated the effects of ebselen, an H(2)O(2) scavenger, on ethanol-induced locomotion. Swiss RjOrl mice were pre-treated with ebselen (0-50mg/kg) intraperitoneally (IP) prior to administration of ethanol (0-3.75g/kg; IP). In another experiment, animals were pre-treated with ebselen (0 or 25mg/kg; IP) before caffeine (15mg/kg; IP), amphetamine (2mg/kg; IP) or cocaine (10mg/kg; IP) administration. Following these treatments, animals were placed in an open field to measure their locomotor activity. Additionally, we evaluated the effect of ebselen on the H(2)O(2)-mediated inactivation of brain catalase activity by 3-amino-1,2,4-triazole (AT). Ebselen selectively prevented ethanol-induced locomotor stimulation without altering the baseline activity or the locomotor stimulating effects caused by caffeine, amphetamine and cocaine. Ebselen reduced the ability of AT to inhibit brain catalase activity. Taken together, these data suggest that a decline in H(2)O(2) levels might result in a reduction of the ethanol locomotor-stimulating effects, indicating a possible role for H(2)O(2) in some of the psychopharmacological effects produced by ethanol. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Ethanol induced hepatic mitochondrial dysfunction is attenuated by all trans retinoic acid supplementation.

Science.gov (United States)

Nair, Saritha S; Prathibha, P; Rejitha, S; Indira, M

2015-08-15

Alcoholics have reduced vitamin A levels in serum since vitamin A and ethanol share the same metabolic pathway. Vitamin A supplementation has an additive effect on ethanol induced toxicity. Hence in this study, we assessed the impact of supplementation of all trans retinoic acid (ATRA), an active metabolite of vitamin A on ethanol induced disruptive alterations in liver mitochondria. Male Sprague Dawley rats were grouped as follows: I: Control; II: Ethanol (4 g/kg b.wt./day); III: ATRA (100 μg/kg b.wt./day); and IV: Ethanol (4 g/kg b.wt./day)+ATRA (100 μg/kg b.wt./day). Duration of the experiment was 90 days, after which the animals were sacrificed for the study. The key enzymes of energy metabolism, reactive oxygen species, mitochondrial membrane potential and hepatic mRNA expressions of Bax, Bcl-2, c-fos and c-jun were assessed. Ethanol administration increased the reactive oxygen species generation in mitochondria. It also decreased the activities of the enzymes of citric acid cycle and oxidative phosphorylation. ATP content and mitochondrial membrane potential were decreased and cytosolic cytochrome c was increased consequently enhancing apoptosis. All these alterations were altered significantly on ATRA supplementation along with ethanol. These results were reinforced by our histopathological studies. ATRA supplementation to ethanol fed rats, led to reduction in oxidative stress, decreased calcium overload in the matrix and increased mitochondrial membrane potential, which might have altered the mitochondrial energy metabolism and elevated ATP production thereby reducing the apoptotic alterations. Hence ATRA supplementation seemed to be an effective intervention against alcohol induced mitochondrial dysfunction. Copyright © 2015 Elsevier Inc. All rights reserved.

miR-217 regulates ethanol-induced hepatic inflammation by disrupting sirtuin 1-lipin-1 signaling.

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Yin, Huquan; Liang, Xiaomei; Jogasuria, Alvin; Davidson, Nicholas O; You, Min

2015-05-01

Ethanol-mediated injury, combined with gut-derived lipopolysaccharide (LPS), provokes generation of proinflammatory cytokines in Kupffer cells, causing hepatic inflammation. Among the mediators of these effects, miR-217 aggravates ethanol-induced steatosis in hepatocytes. However, the role of miR-217 in ethanol-induced liver inflammation process is unknown. Here, we examined the role of miR-217 in the responses to ethanol, LPS, or a combination of ethanol and LPS in RAW 264.7 macrophages and in primary Kupffer cells. In macrophages, ethanol substantially exacerbated LPS-mediated induction of miR-217 and production of proinflammatory cytokines compared with LPS or ethanol alone. Consistently, ethanol administration to mice led to increases in miR-217 abundance and increased production of inflammatory cytokines in isolated primary Kupffer cells exposed to the combination of ethanol and LPS. miR-217 promoted combined ethanol and LPS-mediated inhibition of sirtuin 1 expression and activity in macrophages. Moreover, miR-217-mediated sirtuin 1 inhibition was accompanied by increased activities of two vital inflammatory regulators, NF-κB and the nuclear factor of activated T cells c4. Finally, adenovirus-mediated overexpression of miR-217 led to steatosis and inflammation in mice. These findings suggest that miR-217 is a pivotal regulator involved in ethanol-induced hepatic inflammation. Strategies to inhibit hepatic miR-217 could be a viable approach in attenuating alcoholic hepatitis. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Protective effects of Ginkgo biloba extract on the ethanol-induced gastric ulcer in rats

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Chen, Sheng-Hsuan; Liang, Yu-Chih; Chao, Jane CJ; Tsai, Li-Hsueh; Chang, Chun-Chao; Wang, Chia-Chi; Pan, Shiann

2005-01-01

AIM: To evaluate the preventive effect of Ginkgo biloba extract (GbE) on ethanol-induced gastric mucosal injuries in rats. METHODS: Female Wistar albino rats were used for the studies. We randomly divided the rats for each study into five subgroups: normal control, experimental control, and three experimental groups. The gastric ulcers were induced by instilling 1 mL 50% ethanol into the stomach. We gave GbE 8.75, 17.5, 26.25 mg/kg intravenously to the experimental groups respectively 30 min prior to the ulcerative challenge. We removed the stomachs 45 min later. The gastric ulcers, gastric mucus and the content of non-protein sulfhydryl groups (NP-SH), malondialdehyde (MDA), c-Jun kinase (JNK) activity in gastric mucosa were evaluated. The amount of gastric juice and its acidity were also measured. RESULTS: The findings of our study are as follows: (1) GbE pretreatment was found to provide a dose-dependent protection against the ethanol-induced gastric ulcers in rats; (2) the GbE pretreatment afforded a dose-dependent inhibition of ethanol-induced depletion of stomach wall mucus, NP-SH contents and increase in the lipid peroxidation (increase MDA) in gastric tissue; (3) gastric ulcer induced by ethanol produced an increase in JNK activity in gastric mucosa which also significantly inhibited by pretreatment with GbE; and (4) GbE alone had no inhibitory effect on gastric secretion in pylorus-ligated rats. CONCLUSION: The finding of this study showed that GbE significantly inhibited the ethanol-induced gastric lesions in rats. We suggest that the preventive effect of GbE may be mediated through: (1) inhibition of lipid peroxidation; (2) preservation of gastric mucus and NP-SH; and (3) blockade of cell apoptosis. PMID:15968732

nor-BNI Antagonism of Kappa Opioid Agonist-Induced Reinstatement of Ethanol-Seeking Behavior

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Erin Harshberger

2016-01-01

Full Text Available Recent work suggests that the dynorphin (DYN/kappa opioid receptor (KOR system may be a key mediator in the behavioral effects of alcohol. The objective of the present study was to examine the ability of the KOR antagonist norbinaltorphimine (nor-BNI to attenuate relapse to ethanol seeking due to priming injections of the KOR agonist U50,488 at time points consistent with KOR selectivity. Male Wistar rats were trained to self-administer a 10% ethanol solution, and then responding was extinguished. Following extinction, rats were injected with U50,488 (0.1–10 mg/kg, i.p. or saline and were tested for the reinstatement of ethanol seeking. Next, the ability of the nonselective opioid receptor antagonist naltrexone (0 or 3.0 mg/kg, s.c. and nor-BNI (0 or 20.0 mg/kg, i.p. to block U50,488-induced reinstatement was examined. Priming injections U50,488 reinstated responding on the previously ethanol-associated lever. Pretreatment with naltrexone reduced the reinstatement of ethanol-seeking behavior. nor-BNI also attenuated KOR agonist-induced reinstatement, but to a lesser extent than naltrexone, when injected 24 hours prior to injections of U50,488, a time point that is consistent with KOR selectivity. While these results suggest that activation of KORs is a key mechanism in the regulation of ethanol-seeking behavior, U50,488-induced reinstatement may not be fully selective for KORs.

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

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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®.

The effects of nicotine on ethanol-induced conditioned taste aversions in Long-Evans rats.

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Rinker, Jennifer A; Busse, Gregory D; Roma, Peter G; Chen, Scott A; Barr, Christina S; Riley, Anthony L

2008-04-01

Overall drug acceptability is thought to be a function of the balance between its rewarding and aversive effects, the latter of which is reportedly affected by polydrug use. Given that nicotine and alcohol are commonly co-used, the present experiments sought to assess nicotine's impact on ethanol's aversive effects within a conditioned taste aversion design. Experiment 1 examined various doses of nicotine (0, 0.4, 0.8, 1.2 mg/kg) to determine a behaviorally active dose, and experiment 2 examined various doses of ethanol (0, 0.5, 1.0, 1.5 g/kg) to determine a dose that produced intermediate aversions. Experiment 3 then examined the aversive effects of nicotine (0.8 mg/kg) and ethanol (1.0 g/kg) alone and in combination. Additionally, nicotine's effects on blood alcohol concentrations (BAC) and ethanol-induced hypothermia were examined. Nicotine and ethanol combined produced aversions significantly greater than those produced by either drug alone or the summed aversive effects of the individual compounds. These effects were unrelated to changes in BAC, but nicotine and ethanol combined produced a prolonged hypothermic effect which may contribute to the increased aversions induced by the combination. These data demonstrate that nicotine may interact with ethanol, increasing ethanol's aversive effects. Although the rewarding effects of concurrently administered nicotine and ethanol were not assessed, these data do indicate that the reported high incidence of nicotine and ethanol co-use is unlikely due to reductions in the aversiveness of ethanol with concurrently administered nicotine. It is more likely attributable to nicotine-related changes in ethanol's rewarding effects.

Lever conditioned stimulus-directed autoshaping induced by saccharin-ethanol unconditioned stimulus solution: effects of ethanol concentration and trial spacing.

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Tomie, Arthur; Festa, Eugene D; Sparta, Dennis R; Pohorecky, Larissa A

2003-05-01

Two experiments were designed to evaluate whether brief access to a saccharin-ethanol solution would function as an effective unconditioned stimulus (US) in Pavlovian-autoshaping procedures. In these experiments, the insertion of a lever conditioned stimulus (CS) was followed by the brief presentation of a sipper tube containing saccharin-ethanol US solution. Experience with this Pavlovian-autoshaping procedure engendered lever CS-directed autoshaping conditioned responses (CRs) in all rats. In Experiment 1, the concentration of ethanol [0%, 2%, 4%, 6%, or 8% (vol./vol.)] in 0.1% saccharin was systematically increased within subjects across autoshaping sessions to evaluate the relation between a rat's drinking and lever pressing. In Experiment 2, the mean intertrial interval (ITI) duration (60, 90, 120 s) was systematically increased within subjects across autoshaping sessions to evaluate the effect of ITI duration on drinking and lever pressing. A pseudoconditioning control group received lever CS randomly with respect to the saccharin-ethanol US solution. In Experiment 1, lever-press autoshaping CRs developed in all rats, and the tendency of a rat to drink an ethanol concentration was predictive of the performance of lever-press autoshaping CRs. In Experiment 2, longer ITIs induced more lever CS-directed responding, and CS-US paired procedures yielded more lever CS-directed responding than that observed in CS-US random procedures. Saccharin-ethanol is an effective US in Pavlovian-autoshaping procedures, inducing more CS-directed responding than in pseudoconditioning controls receiving CS-US random procedures. More lever CS-directed responding was observed when there was more drinking of the saccharin-ethanol US solution (Experiment 1); when the CS and US were paired, rather than random (Experiment 2); and with longer mean ITI durations (Experiment 2). This pattern of results is consistent with the hypothesis that lever CS-directed responding reflects performance

Gastroprotective effect of esculin on ethanol-induced gastric lesion in mice.

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Li, Weifeng; Wang, Yu; Wang, Xiumei; Zhang, Hailin; He, Zehong; Zhi, Wenbing; Liu, Fang; Niu, Xiaofeng

2017-04-01

The gastroprotective effect of esculin was investigated in a mouse model of ethanol-induced gastric lesion. Administration of esculin at doses of 5, 10, and 20 mg/kg body weight prior to ethanol ingestion led to significant gastroprotection compared with untreated mice. Gastric mucosal lesions were evaluated by macroscopic and histopathological alterations, lesion index, and myeloperoxidase (MPO) activity. Pretreatment with esculin significantly reduced macroscopic and histopathological damage, gastric lesion index, and MPO activity in a dose-dependent manner. Moreover, esculin significantly reduced nitric oxide (NO) production, inducible NO synthase (iNOS) levels, and nuclear factor-kappa B (NF-κB) p65 protein expression in gastric tissues after ethanol challenge. Analysis of inflammatory cytokines indicated that esculin pretreatment markedly suppressed the increased expression of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in ethanol-treated mice. The results demonstrate a protective effect of esculin against gastric injury and suggest that the underlying mechanism might be associated with inhibition of NF-κB activation, which subsequently reduces expression of iNOS, TNF-α, and IL-6. © 2016 Société Française de Pharmacologie et de Thérapeutique.

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

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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

Protective effect of pyruvate against ethanol-induced apoptotic neurodegeneration in the developing rat brain.

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Ullah, Najeeb; Naseer, Muhammad Imran; Ullah, Ikram; Lee, Hae Young; Koh, Phil Ok; Kim, Myeong Ok

2011-12-01

Exposure to alcohol during the early stages of brain development can lead to neurological disorders in the CNS. Apoptotic neurodegeneration due to ethanol exposure is a main feature of alcoholism. Exposure of developing animals to alcohol (during the growth spurt period in particular) elicits apoptotic neuronal death and causes fetal alcohol effects (FAE) or fetal alcohol syndrome (FAS). A single episode of ethanol intoxication (at 5 g/kg) in a seven-day-old developing rat can activate the apoptotic cascade, leading to widespread neuronal death in the brain. In the present study, we investigated the potential protective effect of pyruvate against ethanol-induced neuroapoptosis. After 4h, a single dose of ethanol induced upregulation of Bax, release of mitochondrial cytochrome-c into the cytosol, activation of caspase-3 and cleavage of poly (ADP-ribose) polymerase (PARP-1), all of which promote apoptosis. These effects were all reversed by co-treatment with pyruvate at a well-tolerated dosage (1000 mg/kg). Histopathology performed at 24 and 48 h with Fluoro-Jade-B and cresyl violet stains showed that pyruvate significantly reduced the number of dead cells in the cerebral cortex, hippocampus and thalamus. Immunohistochemical analysis at 24h confirmed that ethanol-induced cell death is both apoptotic and inhibited by pyruvate. These findings suggest that pyruvate treatment attenuates ethanol-induced neuronal cell loss in the developing rat brain and holds promise as a safe therapeutic and neuroprotective agent in the treatment of neurodegenerative disorders in newborns and infants. Copyright © 2011 Elsevier Ltd. All rights reserved.

Acquisition and reinstatement of ethanol-induced conditioned place preference in rats: Effects of the cholinesterase inhibitors donepezil and rivastigmine.

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Gawel, Kinga; Labuz, Krzysztof; Gibula-Bruzda, Ewa; Jenda, Malgorzata; Marszalek-Grabska, Marta; Silberring, Jerzy; Kotlinska, Jolanta H

2016-07-01

The present study examined the influence of the cholinesterase inhibitors donepezil (a selective inhibitor of acetylcholinesterase) and rivastigmine (also an inhibitor of butyrylcholinesterase) on the acquisition and reinstatement of ethanol-induced conditioned place preference (CPP) in rats. Before the CPP procedure, animals received a single injection of ethanol (0.5 g/kg, 10% w/v, intraperitoneally [i.p.]) for 15 days. The ethanol-induced CPP (biased method) was developed by four injections of ethanol (0.5 g/kg, 10% w/v, i.p.) every second day. Control rats received saline instead of ethanol. Donepezil (0.5, 1 or 3 mg/kg, i.p.) or rivastigmine (0.03, 0.5 or 1 mg/kg, i.p.) were administered before ethanol during conditioning or before the reinstatement of ethanol-induced CPP. The cholinesterase inhibitors were equally effective in increasing (dose dependently) the acquisition of ethanol-induced CPP. Furthermore, priming injections of both inhibitors reinstated (cross-reinstatement) the ethanol-induced CPP with similar efficacy. These effects of both cholinesterase inhibitors were reversed by mecamylamine (3 mg/kg, i.p.), a nicotinic acetylcholine receptor antagonist, but not by scopolamine (0.5 mg/kg, i.p.), a muscarinic acetylcholine receptor antagonist. Thus, our results show that the cholinergic system is involved in the reinforcing properties of ethanol, and nicotinic acetylcholine receptors play an important role in the relapse to ethanol-seeking behaviour. © The Author(s) 2016.

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

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

2017-07-24

Inflammation during brain development participates in the pathogenesis of early brain injury and cognitive dysfunctions. Prenatal ethanol exposure affects the developing brain and causes neural impairment, cognitive and behavioral effects, collectively known as fetal alcohol spectrum disorders (FASD). Our previous studies demonstrate that ethanol activates the innate immune response and TLR4 receptor and causes neuroinflammation, brain damage, and cognitive defects in the developmental brain stage of adolescents. We hypothesize that by activating the TLR4 response, maternal alcohol consumption during pregnancy triggers the release of cytokines and chemokines in both the maternal sera and brains of fetuses/offspring, which impairs brain ontogeny and causes cognitive dysfunction. WT and TLR4-KO female mice treated with or without 10% ethanol in the drinking water during gestation and lactation were used. Cytokine/chemokine levels were determined by ELISA in the amniotic fluid, maternal serum, and cerebral cortex, as well as in the offspring cerebral cortex. Microglial and neuronal markers (evaluated by western blotting), myelin proteins (immunohistochemical and western blotting) and synaptic parameters (western blotting and electron microscopy) were assessed in the cortices of the WT and TLR4-KO pups on PND 0, 20, and 66. Behavioral tests (elevated plus maze and passive avoidance) were performed in the WT and TLR4-KO mice on PND 66 exposed or not to ethanol. We show that alcohol intake during gestation and lactation increases the levels of several cytokines/chemokines (IL-1β, IL-17, MIP-1α, and fractalkine) in the maternal sera, amniotic fluid, and brains of fetuses and offspring. The upregulation of cytokines/chemokines is associated with an increase in activated microglia markers (CD11b and MHC-II), and with a reduction in some synaptic (synaptotagmin, synapsin IIa) and myelin (MBP, PLP) proteins in the brains of offspring on days 0, 20, and 66 (long-term effects

Ethanol enhances arsenic-induced cyclooxygenase-2 expression via both NFAT and NF-κB signalings in colorectal cancer cells

Energy Technology Data Exchange (ETDEWEB)

Wang, Lei; Hitron, John Andrew [Center for Research on Environmental Disease, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Toxicology and Cancer Biology, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Wise, James T.F. [Pharmacology and Nutritional Sciences, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Son, Young-Ok; Roy, Ram Vinod [Center for Research on Environmental Disease, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Toxicology and Cancer Biology, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Kim, Donghern; Dai, Jin [Toxicology and Cancer Biology, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Pratheeshkumar, Poyil [Center for Research on Environmental Disease, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Toxicology and Cancer Biology, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Zhang, Zhuo [Toxicology and Cancer Biology, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Xu, Mei; Luo, Jia [Pharmacology and Nutritional Sciences, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Shi, Xianglin, E-mail: xshi5@uky.edu [Center for Research on Environmental Disease, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Toxicology and Cancer Biology, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States)

2015-10-15

Arsenic is a known carcinogen to humans, and chronic exposure to environmental arsenic is a worldwide health concern. As a dietary factor, ethanol carries a well-established risk for malignancies, but the effects of co-exposure to arsenic and ethanol on tumor development are not well understood. In the present study, we hypothesized that ethanol would enhance the function of an environmental carcinogen such as arsenic through increase in COX-2 expression. Our in vitro results show that ethanol enhanced arsenic-induced COX-2 expression. We also show that the increased COX-2 expression associates with intracellular ROS generation, up-regulated AKT signaling, with activation of both NFAT and NF-κB pathways. We demonstrate that antioxidant enzymes have an inhibitory effect on arsenic/ethanol-induced COX-2 expression, indicating that the responsive signaling pathways from co-exposure to arsenic and ethanol relate to ROS generation. In vivo results also show that co-exposure to arsenic and ethanol increased COX-2 expression in mice. We conclude that ethanol enhances arsenic-induced COX-2 expression in colorectal cancer cells via both the NFAT and NF-κB pathways. These results imply that, as a common dietary factor, ethanol ingestion may be a compounding risk factor for arsenic-induced carcinogenesis/cancer development. - Highlights: • Arsenic is able to induce Cox-2 expression in colorectal cancer cells. • Ethanol, a diet nutritional factor, could enhance arsenic-induced Cox-2. • The up-regulation of Cox-2 via both NFAT and NF-κB activities.

Ethanol enhances arsenic-induced cyclooxygenase-2 expression via both NFAT and NF-κB signalings in colorectal cancer cells

International Nuclear Information System (INIS)

Wang, Lei; Hitron, John Andrew; Wise, James T.F.; Son, Young-Ok; Roy, Ram Vinod; Kim, Donghern; Dai, Jin; Pratheeshkumar, Poyil; Zhang, Zhuo; Xu, Mei; Luo, Jia; Shi, Xianglin

2015-01-01

Arsenic is a known carcinogen to humans, and chronic exposure to environmental arsenic is a worldwide health concern. As a dietary factor, ethanol carries a well-established risk for malignancies, but the effects of co-exposure to arsenic and ethanol on tumor development are not well understood. In the present study, we hypothesized that ethanol would enhance the function of an environmental carcinogen such as arsenic through increase in COX-2 expression. Our in vitro results show that ethanol enhanced arsenic-induced COX-2 expression. We also show that the increased COX-2 expression associates with intracellular ROS generation, up-regulated AKT signaling, with activation of both NFAT and NF-κB pathways. We demonstrate that antioxidant enzymes have an inhibitory effect on arsenic/ethanol-induced COX-2 expression, indicating that the responsive signaling pathways from co-exposure to arsenic and ethanol relate to ROS generation. In vivo results also show that co-exposure to arsenic and ethanol increased COX-2 expression in mice. We conclude that ethanol enhances arsenic-induced COX-2 expression in colorectal cancer cells via both the NFAT and NF-κB pathways. These results imply that, as a common dietary factor, ethanol ingestion may be a compounding risk factor for arsenic-induced carcinogenesis/cancer development. - Highlights: • Arsenic is able to induce Cox-2 expression in colorectal cancer cells. • Ethanol, a diet nutritional factor, could enhance arsenic-induced Cox-2. • The up-regulation of Cox-2 via both NFAT and NF-κB activities.

Modifications in adrenal hormones response to ethanol by prior ethanol dependence.

Science.gov (United States)

Guaza, C; Borrell, S

1985-03-01

Ethanol was administered to rats by means of a liquid diet for 16 days; after an ethanol-free interval of four weeks, animals received a test (IP) dose of ethanol (2 g/kg), and the adrenocortical and adrenomedullary responses were evaluated. Chronically ethanol-exposed animals showed tolerance to the stimulatory effect of ethanol in the pituitary-adrenal axis. Likewise, previously dependent rats showed tolerance to the increase in the activity of the adrenomedullary function induced by acute administration of the drug. Our results indicate that chronic ethanol ingestion can induce persistent changes after complete alcohol abstinence.

Carbon monoxide alleviates ethanol-induced oxidative damage and inflammatory stress through activating p38 MAPK pathway

International Nuclear Information System (INIS)

Li, Yanyan; Gao, Chao; Shi, Yanru; Tang, Yuhan; Liu, Liang; Xiong, Ting; Du, Min; Xing, Mingyou; Liu, Liegang; Yao, Ping

2013-01-01

Stress-inducible protein heme oxygenase-1(HO-1) is well-appreciative to counteract oxidative damage and inflammatory stress involving the pathogenesis of alcoholic liver diseases (ALD). The potential role and signaling pathways of HO-1 metabolite carbon monoxide (CO), however, still remained unclear. To explore the precise mechanisms, ethanol-dosed adult male Balb/c mice (5.0 g/kg.bw.) or ethanol-incubated primary rat hepatocytes (100 mmol/L) were pretreated by tricarbonyldichlororuthenium (II) dimmer (CORM-2, 8 mg/kg for mice or 20 μmol/L for hepatocytes), as well as other pharmacological reagents. Our data showed that CO released from HO-1 induction by quercetin prevented ethanol-derived oxidative injury, which was abolished by CO scavenger hemoglobin. The protection was mimicked by CORM-2 with the attenuation of GSH depletion, SOD inactivation, MDA overproduction, and the leakage of AST, ALT or LDH in serum and culture medium induced by ethanol. Moreover, CORM-2 injection or incubation stimulated p38 phosphorylation and suppressed abnormal Tnfa and IL-6, accompanying the alleviation of redox imbalance induced by ethanol and aggravated by inflammatory factors. The protective role of CORM-2 was abolished by SB203580 (p38 inhibitor) but not by PD98059 (ERK inhibitor) or SP600125 (JNK inhibitor). Thus, HO-1 released CO prevented ethanol-elicited hepatic oxidative damage and inflammatory stress through activating p38 MAPK pathway, suggesting a potential therapeutic role of gaseous signal molecule on ALD induced by naturally occurring phytochemicals. - Highlights: • CO alleviated ethanol-derived liver oxidative and inflammatory stress in mice. • CO eased ethanol and inflammatory factor-induced oxidative damage in hepatocytes. • The p38 MAPK is a key signaling mechanism for the protective function of CO in ALD

Carbon monoxide alleviates ethanol-induced oxidative damage and inflammatory stress through activating p38 MAPK pathway

Energy Technology Data Exchange (ETDEWEB)

Li, Yanyan; Gao, Chao; Shi, Yanru; Tang, Yuhan; Liu, Liang; Xiong, Ting; Du, Min [Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China); Ministry of Education Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China); Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China); Xing, Mingyou [Department of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China); Liu, Liegang [Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China); Ministry of Education Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China); Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China); Yao, Ping, E-mail: yaoping@mails.tjmu.edu.cn [Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China); Ministry of Education Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China); Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China)

2013-11-15

Stress-inducible protein heme oxygenase-1(HO-1) is well-appreciative to counteract oxidative damage and inflammatory stress involving the pathogenesis of alcoholic liver diseases (ALD). The potential role and signaling pathways of HO-1 metabolite carbon monoxide (CO), however, still remained unclear. To explore the precise mechanisms, ethanol-dosed adult male Balb/c mice (5.0 g/kg.bw.) or ethanol-incubated primary rat hepatocytes (100 mmol/L) were pretreated by tricarbonyldichlororuthenium (II) dimmer (CORM-2, 8 mg/kg for mice or 20 μmol/L for hepatocytes), as well as other pharmacological reagents. Our data showed that CO released from HO-1 induction by quercetin prevented ethanol-derived oxidative injury, which was abolished by CO scavenger hemoglobin. The protection was mimicked by CORM-2 with the attenuation of GSH depletion, SOD inactivation, MDA overproduction, and the leakage of AST, ALT or LDH in serum and culture medium induced by ethanol. Moreover, CORM-2 injection or incubation stimulated p38 phosphorylation and suppressed abnormal Tnfa and IL-6, accompanying the alleviation of redox imbalance induced by ethanol and aggravated by inflammatory factors. The protective role of CORM-2 was abolished by SB203580 (p38 inhibitor) but not by PD98059 (ERK inhibitor) or SP600125 (JNK inhibitor). Thus, HO-1 released CO prevented ethanol-elicited hepatic oxidative damage and inflammatory stress through activating p38 MAPK pathway, suggesting a potential therapeutic role of gaseous signal molecule on ALD induced by naturally occurring phytochemicals. - Highlights: • CO alleviated ethanol-derived liver oxidative and inflammatory stress in mice. • CO eased ethanol and inflammatory factor-induced oxidative damage in hepatocytes. • The p38 MAPK is a key signaling mechanism for the protective function of CO in ALD.

Nicotinamide Inhibits Ethanol-Induced Caspase-3 and PARP-1 Over-activation and Subsequent Neurodegeneration in the Developing Mouse Cerebellum.

Science.gov (United States)

Ieraci, Alessandro; Herrera, Daniel G

2018-06-01

Fetal alcohol spectrum disorder (FASD) is the principal preventable cause of mental retardation in the western countries resulting from alcohol exposure during pregnancy. Ethanol-induced massive neuronal cell death occurs mainly in immature neurons during the brain growth spurt period. The cerebellum is one of the brain areas that are most sensitive to ethanol neurotoxicity. Currently, there is no effective treatment that targets the causes of these disorders and efficient treatments to counteract or reverse FASD are desirable. In this study, we investigated the effects of nicotinamide on ethanol-induced neuronal cell death in the developing cerebellum. Subcutaneous administration of ethanol in postnatal 4-day-old mice induced an over-activation of caspase-3 and PARP-1 followed by a massive neurodegeneration in the developing cerebellum. Interestingly, treatment with nicotinamide, immediately or 2 h after ethanol exposure, diminished caspase-3 and PARP-1 over-activation and reduced ethanol-induced neurodegeneration. Conversely, treatment with 3-aminobenzadine, a specific PARP-1 inhibitor, was able to completely block PARP-1 activation, but not caspase-3 activation or ethanol-induced neurodegeneration in the developing cerebellum. Our results showed that nicotinamide reduces ethanol-induced neuronal cell death and inhibits both caspase-3 and PARP-1 alcohol-induced activation in the developing cerebellum, suggesting that nicotinamide might be a promising and safe neuroprotective agent for treating FASD and other neurodegenerative disorders in the developing brain that shares similar cell death pathways.

Fractalkine is a "find-me" signal released by neurons undergoing ethanol-induced apoptosis.

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Sokolowski, Jennifer D; Chabanon-Hicks, Chloe N; Han, Claudia Z; Heffron, Daniel S; Mandell, James W

2014-01-01

Apoptotic neurons generated during normal brain development or secondary to pathologic insults are efficiently cleared from the central nervous system. Several soluble factors, including nucleotides, cytokines, and chemokines are released from injured neurons, signaling microglia to find and clear debris. One such chemokine that serves as a neuronal-microglial communication factor is fractalkine, with roles demonstrated in several models of adult neurological disorders. Lacking, however, are studies investigating roles for fractalkine in perinatal brain injury, an important clinical problem with no effective therapies. We used a well-characterized mouse model of ethanol-induced apoptosis to assess the role of fractalkine in neuronal-microglial signaling. Quantification of apoptotic debris in fractalkine-knockout (KO) and CX3CR1-KO mice following ethanol treatment revealed increased apoptotic bodies compared to wild type mice. Ethanol-induced injury led to release of soluble, extracellular fractalkine. The extracellular media harvested from apoptotic brains induces microglial migration in a fractalkine-dependent manner that is prevented by neutralization of fractalkine with a blocking antibody or by deficiency in the receptor, CX3CR1. This suggests fractalkine acts as a "find-me" signal, recruiting microglial processes toward apoptotic cells to promote their clearance. Next, we aimed to determine whether there are downstream alterations in cytokine gene expression due to fractalkine signaling. We examined mRNA expression in fractalkine-KO and CX3CR1-KO mice after alcohol-induced apoptosis and found differences in cytokine production in the brains of these KOs by 6 h after ethanol treatment. Collectively, this suggests that fractalkine acts as a "find me" signal released by apoptotic neurons, and subsequently plays a critical role in modulating both clearance and inflammatory cytokine gene expression after ethanol-induced apoptosis.

Fractalkine is a "find-me" signal released by neurons undergoing ethanol-induced apoptosis

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Jennifer D Sokolowski

2014-11-01

Full Text Available Apoptotic neurons generated during normal brain development or secondary to pathologic insults are efficiently cleared from the central nervous system. Several soluble factors, including nucleotides, cytokines, and chemokines are released from injured neurons, signaling microglia to find and clear debris. One such chemokine that serves as a neuronal-microglial communication factor is fractalkine, with roles demonstrated in several models of adult neurological disorders. Lacking, however, are studies investigating roles for fractalkine in perinatal brain injury, an important clinical problem with no effective therapies. We used a well-characterized mouse model of ethanol-induced apoptosis to assess the role of fractalkine in neuronal-microglial signaling. Quantification of apoptotic debris in fractalkine-knockout and CX3CR1-knockout mice following ethanol treatment revealed increased apoptotic bodies compared to wild type mice. Ethanol-induced injury led to release of soluble, extracellular fractalkine. The extracellular media harvested from apoptotic brains induces microglial migration in a fractalkine-dependent manner that is prevented by neutralization of fractalkine with a blocking antibody or by deficiency in the receptor, CX3CR1. This suggests fractalkine acts as a ‘find-me’ signal, recruiting microglial processes toward apoptotic cells to promote their clearance. Next, we aimed to determine whether there are downstream alterations in cytokine gene expression due to fractalkine signaling. We examined mRNA expression in fractalkine-knockout and CX3CR1-knockout mice after alcohol-induced apoptosis and found differences in cytokine production in the brains of these knockouts by 6 hours after ethanol treatment. Collectively, this suggests that fractalkine acts as a ‘find me’ signal released by apoptotic neurons, and subsequently plays a critical role in modulating both phagocytic clearance and inflammatory cytokine gene expression after

Chronic psychosocial stress causes delayed extinction and exacerbates reinstatement of ethanol-induced conditioned place preference in mice.

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Bahi, Amine; Dreyer, Jean-Luc

2014-01-01

We have shown previously, using an animal model of voluntary ethanol intake and ethanol-conditioned place preference (EtOH-CPP), that exposure to chronic psychosocial stress induces increased ethanol intake and EtOH-CPP acquisition in mice. Here, we examined the impact of chronic subordinate colony (CSC) exposure on EtOH-CPP extinction, as well as ethanol-induced reinstatement of CPP. Mice were conditioned with saline or 1.5 g/kg ethanol and were tested in the EtOH-CPP model. In the first experiment, the mice were subjected to 19 days of chronic stress, and EtOH-CPP extinction was assessed during seven daily trials without ethanol injection. In the second experiment and after the EtOH-CPP test, the mice were subjected to 7 days of extinction trials before the 19 days of chronic stress. Drug-induced EtOH-CPP reinstatement was induced by a priming injection of 0.5 g/kg ethanol. Compared to the single-housed colony mice, CSC mice exhibited increased anxiety-like behavior in the elevated plus maze (EPM) and the open field tests. Interestingly, the CSC mice showed delayed EtOH-CPP extinction. More importantly, CSC mice showed increased alcohol-induced reinstatement of the EtOH-CPP behavior. Taken together, this study indicates that chronic psychosocial stress can have long-term effects on EtOH-CPP extinction as well as drug-induced reinstatement behavior and may provide a suitable model to study the latent effects of chronic psychosocial stress on extinction and relapse to drug abuse.

Hepatoprotective effect of ethanolic extract of Trichosanthes lobata on paracetamol-induced liver toxicity in rats

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Rajasekaran Aiyalu

2012-05-01

Full Text Available Abstract Background Trichosanthes lobata (family cucurbitaceae is used to treat malarial fever and liver disorders. This study aims to investigate possible hepatoprotective activities of ethanolic extract of Trichosanthes lobata against paracetamol-induced hepatotoxicity. Methods Hepatotoxicity was induced in Wistar male rats by oral administration, 2 g/kg body weight on 7th day after the administration of ethanolic extract of Trichosanthes lobata and silymarin (100 mg/kg. Ethanolic extract of Trichosanthes lobata was administered orally at doses of 200 mg/kg and 400 mg/kg body weight daily for 7 days. Several serum markers, aspartate transaminase, alanine transaminase, alkaline phosphatase, bilirubin, total protein was measured to assess the effect of the extract on paracetamol (acetaminophen-induced hepatic damage. The study included histopathological examination of liver sections. Results Blood samples from rats treated with ethanolic extract of Trichosanthes lobata (200 mg/kg body weight and 400 mg/kg body weight had significant reductions in serum markers in paracetamol administered animals, indicating the effect of the extract in restoring the normal functional ability of hepatocytes. Silymarin (100 mg/kg, p.o. was used as a reference drug. Conclusion The ethanolic extract of Trichosanthes lobata exhibits protective effects against paracetamol‒induced hepatotoxicity.

Chronic ethanol intake induces partial microglial activation that is not reversed by long-term ethanol withdrawal in the rat hippocampal formation.

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Cruz, Catarina; Meireles, Manuela; Silva, Susana M

2017-05-01

Neuroinflammation has been implicated in the pathogenesis of several disorders. Activation of microglia leads to the release of pro-inflammatory mediators and microglial-mediated neuroinflammation has been proposed as one of the alcohol-induced neuropathological mechanisms. The present study aimed to examine the effect of chronic ethanol exposure and long-term withdrawal on microglial activation and neuroinflammation in the hippocampal formation. Male rats were submitted to 6 months of ethanol treatment followed by a 2-month withdrawal period. Stereological methods were applied to estimate the total number of microglia and activated microglia detected by CD11b immunohistochemistry in the hippocampal formation. The expression levels of the pro-inflammatory cytokines TNF-α, COX-2 and IL-15 were measured by qRT-PCR. Alcohol consumption was associated with an increase in the total number of activated microglia but morphological assessment indicated that microglia did not exhibit a full activation phenotype. These data were supported by functional evidence since chronic alcohol consumption produced no changes in the expression of TNF-α or COX-2. The levels of IL-15 a cytokine whose expression is increased upon activation of both astrocytes and microglia, was induced by chronic alcohol treatment. Importantly, the partial activation of microglia induced by ethanol was not reversed by long-term withdrawal. This study suggests that chronic alcohol exposure induces a microglial phenotype consistent with partial activation without significant increase in classical cytokine markers of neuroinflammation in the hippocampal formation. Furthermore, long-term cessation of alcohol intake is not sufficient to alter the microglial partial activation phenotype induced by ethanol. Copyright © 2017 Elsevier B.V. All rights reserved.

Ethanol exposure affects cell movement during gastrulation and induces split axes in zebrafish embryos.

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Zhang, Ying; Shao, Ming; Wang, Lifeng; Liu, Zhongzhen; Gao, Ming; Liu, Chao; Zhang, Hongwei

2010-06-01

To explore the toxic effects of ethanol on axis formation during embryogenesis, zebrafish embryos at different developmental stages were treated with 3% ethanol for 3h. The effects of ethanol exposure appeared to be stage-dependent. The dome stage embryo was most sensible to form posterior split axes upon ethanol exposure. Morphological and histological observations and whole-mount in situ hybridization results showed that ethanol exposure at this stage caused a general gastrulation delay, and induced double notochords, double neural tubes and two sets of somites in the posterior trunk. Mechanistically, no ectopic organizer was found by examining the expression patterns of dorsoventral markers including goosecoid, chordin and eve1 at the onset of gastrulation. However, radial intercalation, epiboly and convergence extension were inhibited by ethanol exposure as revealed by cell labeling, phenotypic observation and the expression patterns of axial or paraxial markers. Further investigation showed that the cell aggregation might be affected by ethanol exposure, as indicated by the much more scattered expression pattern of chordin, eve1 and wnt11 at the early gastrula stage, and the discontinuous gsc positive cells during migration. These results imply that ethanol might affect cell movement before and during gastrulation and as a consequence, induces a split axes phenotype. Copyright 2010 ISDN. Published by Elsevier Ltd. All rights reserved.

Stabilization of Nrf2 protein by D3T provides protection against ethanol-induced apoptosis in PC12 cells.

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Jian Dong

2011-02-01

Full Text Available Previous studies have demonstrated that maternal ethanol exposure induces a moderate increase in Nrf2 protein expression in mouse embryos. Pretreatment with the Nrf2 inducer, 3H-1, 2-dithiole-3-thione (D3T, significantly increases the Nrf2 protein levels and prevents apoptosis in ethanol-exposed embryos. The present study, using PC12 cells, was designed to determine whether increased Nrf2 stability is a mechanism by which D3T enhances Nrf2 activation and subsequent antioxidant protection. Ethanol and D3T treatment resulted in a significant accumulation of Nrf2 protein in PC 12 cells. CHX chase analysis has shown that ethanol treatment delayed the degradation of Nrf2 protein in PC12 cells. A significantly greater decrease in Nrf2 protein degradation was observed in the cells treated with D3T alone or with both ethanol and D3T. In addition, D3T treatment significantly reduced ethanol-induced apoptosis. These results demonstrate that the stabilization of Nrf2 protein by D3T confers protection against ethanol-induced apoptosis.

Ethanol exposure induces the cancer-associated fibroblast phenotype and lethal tumor metabolism: implications for breast cancer prevention.

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Sanchez-Alvarez, Rosa; Martinez-Outschoorn, Ubaldo E; Lin, Zhao; Lamb, Rebecca; Hulit, James; Howell, Anthony; Sotgia, Federica; Rubin, Emanuel; Lisanti, Michael P

2013-01-15

Little is known about how alcohol consumption promotes the onset of human breast cancer(s). One hypothesis is that ethanol induces metabolic changes in the tumor microenvironment, which then enhances epithelial tumor growth. To experimentally test this hypothesis, we used a co-culture system consisting of human breast cancer cells (MCF7) and hTERT-immortalized fibroblasts. Here, we show that ethanol treatment (100 mM) promotes ROS production and oxidative stress in cancer-associated fibroblasts, which is sufficient to induce myofibroblastic differentiation. Oxidative stress in stromal fibroblasts also results in the onset of autophagy/mitophagy, driving the induction of ketone body production in the tumor microenvironment. Interestingly, ethanol has just the opposite effect in epithelial cancer cells, where it confers autophagy resistance, elevates mitochondrial biogenesis and induces key enzymes associated with ketone re-utilization (ACAT1/OXCT1). During co-culture, ethanol treatment also converts MCF7 cells from an ER(+) to an ER(-) status, which is thought to be associated with "stemness," more aggressive behavior and a worse prognosis. Thus, ethanol treatment induces ketone production in cancer-associated fibroblasts and ketone re-utilization in epithelial cancer cells, fueling tumor cell growth via oxidative mitochondrial metabolism (OXPHOS). This "two-compartment" metabolic model is consistent with previous historical observations that ethanol is first converted to acetaldehyde (which induces oxidative stress) and then ultimately to acetyl-CoA (a high-energy mitochondrial fuel), or can be used to synthesize ketone bodies. As such, our results provide a novel mechanism by which alcohol consumption could metabolically convert "low-risk" breast cancer patients to "high-risk" status, explaining tumor recurrence or disease progression. Hence, our findings have clear implications for both breast cancer prevention and therapy. Remarkably, our results also show that

Acute ethanol intake induces superoxide anion generation and mitogen-activated protein kinase phosphorylation in rat aorta: A role for angiotensin type 1 receptor

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Yogi, Alvaro; Callera, Glaucia E. [Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ontario (Canada); Mecawi, André S. [Department of Physiology, Faculty of Medicine of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, SP (Brazil); Batalhão, Marcelo E.; Carnio, Evelin C. [Department of General and Specialized Nursing, College of Nursing of Ribeirão Preto, USP, São Paulo (Brazil); Antunes-Rodrigues, José [Department of Physiology, Faculty of Medicine of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, SP (Brazil); Queiroz, Regina H. [Department of Clinical, Toxicological and Food Science Analysis, Faculty of Pharmaceutical Sciences, USP, São Paulo (Brazil); Touyz, Rhian M. [Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ontario (Canada); Tirapelli, Carlos R., E-mail: crtirapelli@eerp.usp.br [Department of Psychiatric Nursing and Human Sciences, Laboratory of Pharmacology, College of Nursing of Ribeirão Preto, USP, Ribeirão Preto, SP (Brazil)

2012-11-01

Ethanol intake is associated with increase in blood pressure, through unknown mechanisms. We hypothesized that acute ethanol intake enhances vascular oxidative stress and induces vascular dysfunction through renin–angiotensin system (RAS) activation. Ethanol (1 g/kg; p.o. gavage) effects were assessed within 30 min in male Wistar rats. The transient decrease in blood pressure induced by ethanol was not affected by the previous administration of losartan (10 mg/kg; p.o. gavage), a selective AT{sub 1} receptor antagonist. Acute ethanol intake increased plasma renin activity (PRA), angiotensin converting enzyme (ACE) activity, plasma angiotensin I (ANG I) and angiotensin II (ANG II) levels. Ethanol induced systemic and vascular oxidative stress, evidenced by increased plasma thiobarbituric acid-reacting substances (TBARS) levels, NAD(P)H oxidase‐mediated vascular generation of superoxide anion and p47phox translocation (cytosol to membrane). These effects were prevented by losartan. Isolated aortas from ethanol-treated rats displayed increased p38MAPK and SAPK/JNK phosphorylation. Losartan inhibited ethanol-induced increase in the phosphorylation of these kinases. Ethanol intake decreased acetylcholine-induced relaxation and increased phenylephrine-induced contraction in endothelium-intact aortas. Ethanol significantly decreased plasma and aortic nitrate levels. These changes in vascular reactivity and in the end product of endogenous nitric oxide metabolism were not affected by losartan. Our study provides novel evidence that acute ethanol intake stimulates RAS activity and induces vascular oxidative stress and redox-signaling activation through AT{sub 1}-dependent mechanisms. These findings highlight the importance of RAS in acute ethanol-induced oxidative damage. -- Highlights: ► Acute ethanol intake stimulates RAS activity and vascular oxidative stress. ► RAS plays a role in acute ethanol-induced oxidative damage via AT{sub 1} receptor activation. �

Protective effect of arctigenin on ethanol-induced neurotoxicity in PC12 cells.

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Huang, Jia; Xiao, Lan; Wei, Jing-Xiang; Shu, Ya-Hai; Fang, Shi-Qi; Wang, Yong-Tang; Lu, Xiu-Min

2017-04-01

As a neurotropic substance, ethanol can damage nerve cells through an increase in the production of free radicals, interference of neurotrophic factor signaling pathways, activation of endogenous apoptotic signals and other molecular mechanisms. Previous studies have revealed that a number of natural drugs extracted from plants offer protection of nerve cells from damage. Among these, arctigenin (ATG) is a lignine extracted from Arctium lappa (L.), which has been found to exert a neuroprotective effect on scopolamine‑induced memory deficits in mice with Alzheimer's disease and glutamate-induced neurotoxicity in primary neurons. As a result, it may offer beneficial effects on ethanol-induced neurotoxicity. However, the effects of ATG on ethanol‑induced nerve damage remain to be elucidated. To address this issue, the present study used rat pheochromocytoma PC12 cells to investigate the neuroprotective effects of ATG on ethanol-induced cell damage by performing an MTT reduction assay, cell cycle analysis, Hoechst33342/propidium iodide fluorescence staining and flow cytometry to examine apoptosis. The results showed that 10 µM ATG effectively promoted the proliferation of damaged cells, and increased the distribution ratio of the cells at the G2/M and S phases (P<0.05). In addition, the apoptosis and necrosis of the PC12 cells were significantly decreased following treatment with ATG. Therefore, it was concluded that 10 µM ATG had a protective effect on ethanol‑induced injury in PC12 cells.

alpha7 Nicotinic acetylcholine receptor knockout selectively enhances ethanol-, but not beta-amyloid-induced neurotoxicity.

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de Fiebre, Nancyellen C; de Fiebre, Christopher M

2005-01-03

The alpha7 subtype of nicotinic acetylcholine receptor (nAChR) has been implicated as a potential site of action for two neurotoxins, ethanol and the Alzheimer's disease related peptide, beta-amyloid. Here, we utilized primary neuronal cultures of cerebral cortex from alpha7 nAChR null mutant mice to examine the role of this receptor in modulating the neurotoxic properties of subchronic, "binge" ethanol and beta-amyloid. Knockout of the alpha7 nAChR gene selectively enhanced ethanol-induced neurotoxicity in a gene dosage-related fashion. Susceptibility of cultures to beta-amyloid induced toxicity, however, was unaffected by alpha7 nAChR gene null mutation. Further, beta-amyloid did not inhibit the binding of the highly alpha7-selective radioligand, [(125)I]alpha-bungarotoxin. On the other hand, in studies in Xenopus oocytes ethanol efficaciously inhibited alpha7 nAChR function. These data suggest that alpha7 nAChRs modulate the neurotoxic effects of binge ethanol, but not the neurotoxicity produced by beta-amyloid. It is hypothesized that inhibition of alpha7 nAChRs by ethanol provides partial protection against the neurotoxic properties of subchronic ethanol.

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

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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.

Ameliorative effect of Opuntia ficus indica juice on ethanol-induced oxidative stress in rat erythrocytes.

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Alimi, Hichem; Hfaeidh, Najla; Bouoni, Zouhour; Sakly, Mohsen; Rhouma, Khémais Ben

2013-05-01

The aim of the present study was to investigate the efficacy of Opuntia ficus indica f. inermis fruit juice (OFIj) on reversing oxidative damages induced by chronic ethanol intake in rat erythrocytes. OFIj was firstly analyzed with HPLC for phenolic and flavonoids content. Secondly, 40 adult male Wistar rats were equally divided into five groups and treated for 90 days as follows: control (C), ethanol-only 3 g/kg body weight (b.w) (E), low dose of OFIj 2 ml/100 g b.w+ethanol (Ldj+E), high dose of OFIj 4 ml/100 g b.w+ethanol (Hdj+E), and only a high dose of OFIj 4 ml/100g b.w (Hdj). HPLC analysis indicated high concentrations of phenolic acids and flavonoids in OFIj. Ethanol treatment markedly decreased the activities of erythrocyte superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), and the level of reduced glutathione (GSH). Changes in the erythrocyte's antioxidant ability were accompanied by enhanced oxidative modification of lipids (increase of malondialdeyde level) and proteins (increase in carbonyl groups). Interestingly, pre-administration of either 2 ml/100 g b.w or 4 ml/100 g b.w of OFIj to ethanol-intoxicated rats significantly reversed decreases in enzymatic as well as non enzymatic antioxidants parameters in erythrocytes. Also, the administration of OFIj significantly protected lipids and proteins against ethanol-induced oxidative modifications in rat erythrocytes. The beneficial effect of OFIj can result from the inhibition of ethanol-induced free radicals chain reactions in rat erythrocytes or from the enhancement of the endogenous antioxidants activities. Copyright © 2011 Elsevier GmbH. All rights reserved.

Ethanol Induced Urine Acidification is Related with Early Acetaldehyde Concentration

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Soon Kil Kwon

2014-06-01

Conclusion: In conclusion, urine acidification after ethanol ingestion is related with serum acetaldehyde concentration. Early elevation of acetaldhyde could induce urine acidification, but the urine pH was elevated after a few hours, that might make prolonged acidemia.

Moderate ethanol administration accentuates cardiomyocyte contractile dysfunction and mitochondrial injury in high fat diet-induced obesity.

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Yuan, Fang; Lei, Yonghong; Wang, Qiurong; Esberg, Lucy B; Huang, Zaixing; Scott, Glenda I; Li, Xue; Ren, Jun

2015-03-18

Light to moderate drinking confers cardioprotection although it remains unclear with regards to the role of moderate drinking on cardiac function in obesity. This study was designed to examine the impact of moderate ethanol intake on myocardial function in high fat diet intake-induced obesity and the mechanism(s) involved with a focus on mitochondrial integrity. C57BL/6 mice were fed low or high fat diet for 16 weeks prior to ethanol challenge (1g/kg/d for 3 days). Cardiac contractile function, intracellular Ca(2+) homeostasis, myocardial histology, and mitochondrial integrity [aconitase activity and the mitochondrial proteins SOD1, UCP-2 and PPARγ coactivator 1α (PGC-1α)] were assessed 24h after the final ethanol challenge. Fat diet intake compromised cardiomyocyte contractile and intracellular Ca(2+) properties (depressed peak shortening and maximal velocities of shortening/relengthening, prolonged duration of relengthening, dampened intracellular Ca(2+) rise and clearance without affecting duration of shortening). Although moderate ethanol challenge failed to alter cardiomyocyte mechanical property under low fat diet intake, it accentuated high fat diet intake-induced changes in cardiomyocyte contractile function and intracellular Ca(2+) handling. Moderate ethanol challenge failed to affect fat diet intake-induced cardiac hypertrophy as evidenced by H&E staining. High fat diet intake reduced myocardial aconitase activity, downregulated levels of mitochondrial protein UCP-2, PGC-1α, SOD1 and interrupted intracellular Ca(2+) regulatory proteins, the effect of which was augmented by moderate ethanol challenge. Neither high fat diet intake nor moderate ethanol challenge affected protein or mRNA levels as well as phosphorylation of Akt and GSK3β in mouse hearts. Taken together, our data revealed that moderate ethanol challenge accentuated high fat diet-induced cardiac contractile and intracellular Ca(2+) anomalies as well as mitochondrial injury. Copyright �

Lead Intoxication Synergies of the Ethanol-Induced Toxic Responses in Neuronal Cells--PC12.

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Kumar, V; Tripathi, V K; Jahan, S; Agrawal, M; Pandey, A; Khanna, V K; Pant, A B

2015-12-01

Lead (Pb)-induced neurodegeneration and its link with widespread neurobehavioral changes are well documented. Experimental evidences suggest that ethanol could enhance the absorption of metals in the body, and alcohol consumption may increase the susceptibility to metal intoxication in the brain. However, the underlying mechanism of ethanol action in affecting metal toxicity in brain cells is poorly understood. Thus, an attempt was made to investigate the modulatory effect of ethanol on Pb intoxication in PC12 cells, a rat pheochromocytoma. Cells were co-exposed to biological safe doses of Pb (10 μM) and ethanol (200 mM), and data were compared to the response of cells which received independent exposure to these chemicals at similar doses. Ethanol (200 mM) exposure significantly aggravated the Pb-induced alterations in the end points associated with oxidative stress and apoptosis. The finding confirms the involvement of reactive oxygen species (ROS)-mediated oxidative stress, and impairment of mitochondrial membrane potential, which subsequently facilitate the translocation of triggering proteins between cytoplasm and mitochondria. We further confirmed the apoptotic changes due to induction of mitochondria-mediated caspase cascade. These cellular changes were found to recover significantly, if the cells are exposed to N-acetyl cysteine (NAC), a known antioxidant. Our data suggest that ethanol may potentiate Pb-induced cellular damage in brain cells, but such damaging effects could be recovered by inhibition of ROS generation. These results open up further possibilities for the design of new therapeutics based on antioxidants to prevent neurodegeneration and associated health problems.

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

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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.

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

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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.

Protective effects of resveratrol on ethanol-induced apoptosis in embryonic stem cells and disruption of embryonic development in mouse blastocysts

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Huang, L.-H.; Shiao, N.-H.; Hsuuw, Y.-D.; Chan, W.-H.

2007-01-01

Previous studies have established that ethanol induces apoptosis, but the precise molecular mechanisms are currently unclear. Here, we show that 0.3-1.0% (w/v) ethanol induces apoptosis in mouse blastocysts and that resveratrol, a grape-derived phytoalexin with known antioxidant and anti-inflammatory properties, prevents ethanol-induced apoptosis and inhibition of cell proliferation. Moreover, ethanol-treated blastocysts show normal levels of implantation on culture dishes in vitro but a reduced ability to reach the later stages of embryonic development. Pretreatment with resveratrol prevented ethanol-induced disruption of embryonic development in vitro and in vivo. In an in vitro cell-based assay, we further found that ethanol increases the production of reactive oxygen species in ESC-B5 embryonic stem cells, leading to an increase in the intracellular concentrations of cytoplasmic free Ca 2+ and NO, loss of mitochondrial membrane potential, mitochondrial release of cytochrome c, activation of caspase-9 and -3, and apoptosis. These changes were blocked by pretreatment with resveratrol. Based on these results, we propose a model for the protective effect of resveratrol on ethanol-induced cell injury in blastocysts and ESC-B5 cells

The ethanol-induced stimulation of rat duodenal mucosal bicarbonate secretion in vivo is critically dependent on luminal Cl-.

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Anna Sommansson

Full Text Available Alcohol may induce metabolic and functional changes in gastrointestinal epithelial cells, contributing to impaired mucosal barrier function. Duodenal mucosal bicarbonate secretion (DBS is a primary epithelial defense against gastric acid and also has an important function in maintaining the homeostasis of the juxtamucosal microenvironment. The aim in this study was to investigate the effects of the luminal perfusion of moderate concentrations of ethanol in vivo on epithelial DBS, fluid secretion and paracellular permeability. Under thiobarbiturate anesthesia, a ∼30-mm segment of the proximal duodenum with an intact blood supply was perfused in situ in rats. The effects on DBS, duodenal transepithelial net fluid flux and the blood-to-lumen clearance of 51Cr-EDTA were investigated. Perfusing the duodenum with isotonic solutions of 10% or 15% ethanol-by-volume for 30 min increased DBS in a concentration-dependent manner, while the net fluid flux did not change. Pre-treatment with the CFTR inhibitor CFTRinh172 (i.p. or i.v. did not change the secretory response to ethanol, while removing Cl- from the luminal perfusate abolished the ethanol-induced increase in DBS. The administration of hexamethonium (i.v. but not capsazepine significantly reduced the basal net fluid flux and the ethanol-induced increase in DBS. Perfusing the duodenum with a combination of 1.0 mM HCl and 15% ethanol induced significantly greater increases in DBS than 15% ethanol or 1.0 mM HCl alone but did not influence fluid flux. Our data demonstrate that ethanol induces increases in DBS through a mechanism that is critically dependent on luminal Cl- and partly dependent on enteric neural pathways involving nicotinic receptors. Ethanol and HCl appears to stimulate DBS via the activation of different bicarbonate transporting mechanisms.

Effects of the mGluR5 antagonist MPEP on ethanol withdrawal induced anxiety-like syndrome in rats.

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Kumar, Jaya; Hapidin, Hermizi; Bee, Yvonne-Tee Get; Ismail, Zalina

2013-11-26

Abstinence from chronic ethanol consumption leads to the manifestation of a variety of symptoms attributed to central nervous system hyperexcitability, such as increased irritability, anxiety, and restlessness. Recent studies have demonstrated the importance of metabotropic glutamate receptor 5 (mGluR5) in addictive behaviours. This study investigates the effects of the mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) on ethanol withdrawal induced anxiety using two behavioural paradigms. Male Wistar rats were fed a Modified Liquid Diet (MLD) containing low fat cow milk, sucrose, and maltodextrin with a gradual introduction of 2.4%, 4.8% and 7.2% ethanol for 20 days. Six hours into ethanol withdrawal, the rats were intraperitoneally injected with normal saline and MPEP (2.5, 5.0, 10, 20, 30 mg/kg) and were assessed for ethanol withdrawal induced anxiety-like syndrome using an automated elevated plus maze and an open field. MPEP at 10 mg/kg significantly attenuated ethanol withdrawal induced anxiety without any compromising effects on locomotor activities. Despite reversing several indices of ethanol withdrawal induced anxiety in both the elevated plus maze and the open field, low doses of MPEP (2.5, 5 mg/kg) significantly compromised the locomotor activities of ethanol withdrawn rats. High doses of MPEP (20 and 30 mg/kg) significantly attenuated withdrawal anxiety when tested in the elevated plus maze but not in the open field. Administration of MPEP (2.5, 5, 10, 20, 30 mg/kg) has no significant compromising effect on the locomotor activities of ethanol naïve rats. Despite significantly reducing withdrawal anxiety in both behavioural paradigms at 10 mg/kg, the compromising effects of low and high doses of MPEP must be further explored along with the therapeutic efficiency of this drug for relieving withdrawal induced anxiety.

Participation of the cholinergic system in the ethanol-induced suppression of paradoxical sleep in rats

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L.A. Papale

2008-09-01

Full Text Available Sleep disturbance is among the many consequences of ethanol abuse in both humans and rodents. Ethanol consumption can reduce REM or paradoxical sleep (PS in humans and rats, respectively. The first aim of this study was to develop an animal model of ethanol-induced PS suppression. This model administered intragastrically (by gavage to male Wistar rats (3 months old, 200-250 g 0.5 to 3.5 g/kg ethanol. The 3.5 g/kg dose of ethanol suppressed the PS stage compared with the vehicle group (distilled water during the first 2-h interval (0-2 h; 1.3 vs 10.2; P < 0.001. The second aim of this study was to investigate the mechanisms by which ethanol suppresses PS. We examined the effects of cholinergic drug pretreatment. The cholinergic system was chosen because of the involvement of cholinergic neurotransmitters in regulating the sleep-wake cycle. A second set of animals was pretreated with 2.5, 5.0, and 10 mg/kg pilocarpine (cholinergic agonist or atropine (cholinergic antagonist. These drugs were administered 1 h prior to ethanol (3.5 g/kg or vehicle. Treatment with atropine prior to vehicle or ethanol produced a statistically significant decrease in PS, whereas pilocarpine had no effect on minutes of PS. Although the mechanism by which ethanol induces PS suppression is not fully understood, these data suggest that the cholinergic system is not the only system involved in this interaction.

Effects of ethanol and acetaldehyde on tight junction integrity: in vitro study in a three dimensional intestinal epithelial cell culture model.

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Elhaseen Elamin

Full Text Available BACKGROUND: Intestinal barrier dysfunction and translocation of endotoxins are involved in the pathogenesis of alcoholic liver disease. Exposure to ethanol and its metabolite, acetaldehyde at relatively high concentrations have been shown to disrupt intestinal epithelial tight junctions in the conventional two dimensional cell culture models. The present study investigated quantitatively and qualitatively the effects of ethanol at concentrations detected in the blood after moderate ethanol consumption, of its metabolite acetaldehyde and of the combination of both compounds on intestinal barrier function in a three-dimensional cell culture model. METHODS AND FINDINGS: Caco-2 cells were grown in a basement membrane matrix (Matrigel™ to induce spheroid formation and were then exposed to the compounds at the basolateral side. Morphological differentiation of the spheroids was assessed by immunocytochemistry and transmission electron microscopy. The barrier function was assessed by the flux of FITC-labeled dextran from the basal side into the spheroids' luminal compartment using confocal microscopy. Caco-2 cells grown on Matrigel assembled into fully differentiated and polarized spheroids with a central lumen, closely resembling enterocytes in vivo and provide an excellent model to study epithelial barrier functionality. Exposure to ethanol (10-40 mM or acetaldehyde (25-200 µM for 3 h, dose-dependently and additively increased the paracellular permeability and induced redistribution of ZO-1 and occludin without affecting cell viability or tight junction-encoding gene expression. Furthermore, ethanol and acetaldehyde induced lysine residue and microtubules hyperacetylation. CONCLUSIONS: These results indicate that ethanol at concentrations found in the blood after moderate drinking and acetaldehyde, alone and in combination, can increase the intestinal epithelial permeability. The data also point to the involvement of protein hyperacetylation in

Ethanol injected into the hypothalamic arcuate nucleus induces behavioral stimulation in rats: an effect prevented by catalase inhibition and naltrexone.

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Pastor, Raúl; Aragon, Carlos M G

2008-10-01

It is suggested that some of the behavioral effects of ethanol, including its psychomotor properties, are mediated by beta-endorphin and opioid receptors. Ethanol-induced increases in the release of hypothalamic beta-endorphin depend on the catalasemic conversion of ethanol to acetaldehyde. Here, we evaluated the locomotor activity in rats microinjected with ethanol directly into the hypothalamic arcuate nucleus (ArcN), the main site of beta-endorphin synthesis in the brain and a region with high levels of catalase expression. Intra-ArcN ethanol-induced changes in motor activity were also investigated in rats pretreated with the opioid receptor antagonist, naltrexone (0-2 mg/kg) or the catalase inhibitor 3-amino-1,2,4-triazole (AT; 0-1 g/kg). We found that ethanol microinjections of 64 or 128, but not 256 microg, produced locomotor stimulation. Intra-ArcN ethanol (128 microg)-induced activation was prevented by naltrexone and AT, whereas these compounds did not affect spontaneous activity. The present results support earlier evidence indicating that the ArcN and the beta-endorphinic neurons of this nucleus are necessary for ethanol to induce stimulation. In addition, our data suggest that brain structures that, as the ArcN, are rich in catalase may support the formation of ethanol-derived pharmacologically relevant concentrations of acetaldehyde and, thus be of particular importance for the behavioral effects of ethanol.

DNA adsorption and desorption on mica surface studied by atomic force microscopy

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Sun Lanlan [State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Graduate school of the Chinese Academy of Sciences, Chinese Academy of Sciences, Renmin Street 5625, Changchun 130022 (China); Key Laboratory of Excited State Processes, Changchun Institute of Optics, Fine Mechanics and Physics, Chinese Academy of Sciences, 16 East Nan-Hu Road, Open Economic Zone, Changchun 130033 (China); Zhao Dongxu [Key Laboratory of Excited State Processes, Changchun Institute of Optics, Fine Mechanics and Physics, Chinese Academy of Sciences, 16 East Nan-Hu Road, Open Economic Zone, Changchun 130033 (China); Zhang Yue; Xu Fugang [State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Graduate school of the Chinese Academy of Sciences, Chinese Academy of Sciences, Renmin Street 5625, Changchun 130022 (China); Li Zhuang, E-mail: zli@ciac.jl.cn [State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Graduate school of the Chinese Academy of Sciences, Chinese Academy of Sciences, Renmin Street 5625, Changchun 130022 (China)

2011-05-15

The adsorption of DNA molecules on mica surface and the following desorption of DNA molecules at ethanol-mica interface were studied using atomic force microscopy. By changing DNA concentration, different morphologies on mica surface have been observed. A very uniform and orderly monolayer of DNA molecules was constructed on the mica surface with a DNA concentration of 30 ng/{mu}L. When the samples were immersed into ethanol for about 15 min, various desorption degree of DNA from mica (0-99%) was achieved. It was found that with the increase of DNA concentration, the desorption degree of DNA from the mica at ethanol-mica interface decreased. And when the uniform and orderly DNA monolayers were formed on the mica surface, almost no DNA molecule desorbed from the mica surface in this process. The results indicated that the uniform and orderly DNA monolayer is one of the most stable DNA structures formed on the mica surface. In addition, we have studied the structure change of DNA molecules after desorbed from the mica surface with atomic force microscopy, and found that the desorption might be ascribed to the ethanol-induced DNA condensation.

DNA adsorption and desorption on mica surface studied by atomic force microscopy

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Sun Lanlan; Zhao Dongxu; Zhang Yue; Xu Fugang; Li Zhuang

2011-01-01

The adsorption of DNA molecules on mica surface and the following desorption of DNA molecules at ethanol-mica interface were studied using atomic force microscopy. By changing DNA concentration, different morphologies on mica surface have been observed. A very uniform and orderly monolayer of DNA molecules was constructed on the mica surface with a DNA concentration of 30 ng/μL. When the samples were immersed into ethanol for about 15 min, various desorption degree of DNA from mica (0-99%) was achieved. It was found that with the increase of DNA concentration, the desorption degree of DNA from the mica at ethanol-mica interface decreased. And when the uniform and orderly DNA monolayers were formed on the mica surface, almost no DNA molecule desorbed from the mica surface in this process. The results indicated that the uniform and orderly DNA monolayer is one of the most stable DNA structures formed on the mica surface. In addition, we have studied the structure change of DNA molecules after desorbed from the mica surface with atomic force microscopy, and found that the desorption might be ascribed to the ethanol-induced DNA condensation.

Binge Ethanol and MDMA Combination Exacerbates Toxic Cardiac Effects by Inducing Cellular Stress

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Navarro-Zaragoza, Javier; Ros-Simó, Clara; Milanés, María-Victoria; Valverde, Olga; Laorden, María-Luisa

2015-01-01

Binge drinking is a common pattern of ethanol consumption among young people. Binge drinkers are especially susceptible to brain damage when other substances are co-administered, in particular 3,4 methylendioxymethamphetamine (MDMA). The aim of the present work was to study the mechanisms implicated in the adaptive changes observed after administration of these drugs of abuse. So, we have evaluated the cardiac sympathetic activity and the expression and activation of heat shock protein 27 (HSP27), after voluntary binge ethanol consumption, alone and in combination with MDMA. Both parameters are markers of stressful situations and they could be modified inducing several alterations in different systems. Adolescent mice received MDMA, ethanol or both (ethanol plus MDMA). Drinking in the dark (DID) procedure was used as a model of binge. Noradrenaline (NA) turnover, tyrosine hydroxylase (TH), TH phosphorylated at serine 31 and HSP27 expression and its phosphorylation at serine 82 were evaluated in adolescent mice 48 h, 72 h, and 7 days after treatments in the left ventricle. NA and normetanephrine (NMN) were determined by high-performance liquid chromatography (HPLC); TH and HSP27 expression and phosphorylation were measured by quantitative blot immunollabeling using specific antibodies. Ethanol and MDMA co-administration increased NA turnover and TH expression and phosphorylation versus the consumption of each one of these drugs. In parallel with the described modifications in the cardiac sympathetic activity, our results showed that binge ethanol+MDMA exposure is associated with an increase in HSP27 expression and phosphorylation in the left ventricle, supporting the idea that the combination of both drugs exacerbates the cellular stress induced by ethanol or MDMA alone. PMID:26509576

Binge Ethanol and MDMA Combination Exacerbates Toxic Cardiac Effects by Inducing Cellular Stress.

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Javier Navarro-Zaragoza

Full Text Available Binge drinking is a common pattern of ethanol consumption among young people. Binge drinkers are especially susceptible to brain damage when other substances are co-administered, in particular 3,4 methylendioxymethamphetamine (MDMA. The aim of the present work was to study the mechanisms implicated in the adaptive changes observed after administration of these drugs of abuse. So, we have evaluated the cardiac sympathetic activity and the expression and activation of heat shock protein 27 (HSP27, after voluntary binge ethanol consumption, alone and in combination with MDMA. Both parameters are markers of stressful situations and they could be modified inducing several alterations in different systems. Adolescent mice received MDMA, ethanol or both (ethanol plus MDMA. Drinking in the dark (DID procedure was used as a model of binge. Noradrenaline (NA turnover, tyrosine hydroxylase (TH, TH phosphorylated at serine 31 and HSP27 expression and its phosphorylation at serine 82 were evaluated in adolescent mice 48 h, 72 h, and 7 days after treatments in the left ventricle. NA and normetanephrine (NMN were determined by high-performance liquid chromatography (HPLC; TH and HSP27 expression and phosphorylation were measured by quantitative blot immunollabeling using specific antibodies. Ethanol and MDMA co-administration increased NA turnover and TH expression and phosphorylation versus the consumption of each one of these drugs. In parallel with the described modifications in the cardiac sympathetic activity, our results showed that binge ethanol+MDMA exposure is associated with an increase in HSP27 expression and phosphorylation in the left ventricle, supporting the idea that the combination of both drugs exacerbates the cellular stress induced by ethanol or MDMA alone.

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

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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.

Vacuolar H+-ATPase Protects Saccharomyces cerevisiae Cells against Ethanol-Induced Oxidative and Cell Wall Stresses.

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Charoenbhakdi, Sirikarn; Dokpikul, Thanittra; Burphan, Thanawat; Techo, Todsapol; Auesukaree, Choowong

2016-05-15

During fermentation, increased ethanol concentration is a major stress for yeast cells. Vacuolar H(+)-ATPase (V-ATPase), which plays an important role in the maintenance of intracellular pH homeostasis through vacuolar acidification, has been shown to be required for tolerance to straight-chain alcohols, including ethanol. Since ethanol is known to increase membrane permeability to protons, which then promotes intracellular acidification, it is possible that the V-ATPase is required for recovery from alcohol-induced intracellular acidification. In this study, we show that the effects of straight-chain alcohols on membrane permeabilization and acidification of the cytosol and vacuole are strongly dependent on their lipophilicity. These findings suggest that the membrane-permeabilizing effect of straight-chain alcohols induces cytosolic and vacuolar acidification in a lipophilicity-dependent manner. Surprisingly, after ethanol challenge, the cytosolic pH in Δvma2 and Δvma3 mutants lacking V-ATPase activity was similar to that of the wild-type strain. It is therefore unlikely that the ethanol-sensitive phenotype of vma mutants resulted from severe cytosolic acidification. Interestingly, the vma mutants exposed to ethanol exhibited a delay in cell wall remodeling and a significant increase in intracellular reactive oxygen species (ROS). These findings suggest a role for V-ATPase in the regulation of the cell wall stress response and the prevention of endogenous oxidative stress in response to ethanol. The yeast Saccharomyces cerevisiae has been widely used in the alcoholic fermentation industry. Among the environmental stresses that yeast cells encounter during the process of alcoholic fermentation, ethanol is a major stress factor that inhibits yeast growth and viability, eventually leading to fermentation arrest. This study provides evidence for the molecular mechanisms of ethanol tolerance, which is a desirable characteristic for yeast strains used in alcoholic

Memantine Can Reduce Ethanol-Induced Caspase-3 Activity and Apoptosis in H4 Cells by Decreasing Intracellular Calcium.

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Wang, Xiaolong; Chen, Jiajun; Wang, Hongbo; Yu, Hao; Wang, Changliang; You, Jiabin; Wang, Pengfei; Feng, Chunmei; Xu, Guohui; Wu, Xu; Zhao, Rui; Zhang, Guohua

2017-08-01

Caspase-3 activation and apoptosis are associated with various neurodegenerative disorders. Calcium activation is an important factor in promoting apoptosis. We, therefore, assessed the role of intracellular calcium in ethanol-induced activation of caspase-3 in H4 human neuroglioma cells and the protective effect of the NMDA receptor antagonist, memantine, on ethanol-induced apoptosis in H4 cells. H4 cells were treated with 100 mM EtOH (in culture medium) for 2 days. For interaction studies, cells were treated with memantine (4 μM), EDTA (1 mM), or BAPTA-AM (10 μM) before treatment with EtOH. Knockdown of the gene encoding the NR1 subunit of the NMDA receptor was performed using RNAi. Apoptosis was detected by Annexin V-FITC/PI staining and flow cytometry. Cell viability was detected using an MTS cell proliferation kit. Fluorescence dual wavelength spectrophotometry was used to determine the intracellular calcium concentration. The levels of NR1, caspase-3, IP3R1, and SERCA1 proteins were detected by western blotting. NR1, IP3R1, and SERCA1 mRNA levels were detected by qPCR. We observed increased expression of NR1, IP3R1, SERCA1, and increased intracellular levels of calcium ions in H4 cells exposed to ethanol. In addition, the calcium chelators, EDTA and BAPTA, and RNAi disruption of the NMDA receptor reduced ethanol-induced caspase-3 activation in H4 cells. Memantine treatment reduced the ethanol-induced increase of intracellular calcium, caspase-3 activation, apoptosis, and the ethanol-induced decrease in cell viability. Our results indicate that ethanol-induced caspase-3 activation and apoptosis are likely to be dependent on cytosolic calcium levels and that they can be reduced by memantine treatment.

Neuroprotection with metformin and thymoquinone against ethanol-induced apoptotic neurodegeneration in prenatal rat cortical neurons

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Ullah Ikram

2012-01-01

Full Text Available Abstract Background Exposure to ethanol during early development triggers severe neuronal death by activating multiple stress pathways and causes neurological disorders, such as fetal alcohol effects or fetal alcohol syndrome. This study investigated the effect of ethanol on intracellular events that predispose developing neurons for apoptosis via calcium-mediated signaling. Although the underlying molecular mechanisms of ethanol neurotoxicity are not completely determined, mitochondrial dysfunction, altered calcium homeostasis and apoptosis-related proteins have been implicated in ethanol neurotoxicity. The present study was designed to evaluate the neuroprotective mechanisms of metformin (Met and thymoquinone (TQ during ethanol toxicity in rat prenatal cortical neurons at gestational day (GD 17.5. Results We found that Met and TQ, separately and synergistically, increased cell viability after ethanol (100 mM exposure for 12 hours and attenuated the elevation of cytosolic free calcium [Ca2+]c. Furthermore, Met and TQ maintained normal physiological mitochondrial transmembrane potential (ΔψM, which is typically lowered by ethanol exposure. Increased cytosolic free [Ca2+]c and lowered mitochondrial transmembrane potential after ethanol exposure significantly decreased the expression of a key anti-apoptotic protein (Bcl-2, increased expression of Bax, and stimulated the release of cytochrome-c from mitochondria. Met and TQ treatment inhibited the apoptotic cascade by increasing Bcl-2 expression. These compounds also repressed the activation of caspase-9 and caspase-3 and reduced the cleavage of PARP-1. Morphological conformation of cell death was assessed by TUNEL, Fluoro-Jade-B, and PI staining. These staining methods demonstrated more cell death after ethanol treatment, while Met, TQ or Met plus TQ prevented ethanol-induced apoptotic cell death. Conclusion These findings suggested that Met and TQ are strong protective agents against ethanol-induced

Study of surface damage on cell envelope assessed by AFM and flow cytometry of Lactobacillus plantarum exposed to ethanol and dehydration.

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Bravo-Ferrada, B M; Gonçalves, S; Semorile, L; Santos, N C; Tymczyszyn, E E; Hollmann, A

2015-06-01

In this work, we evaluated freeze-drying damage at the surface level of oenological strain Lactobacillus plantarum UNQLp155, as well as its ability to grow in a synthetic wine with and without pre-acclimation. Damage on cell surface was studied by flow cytometry, zeta potential and atomic force microscopy, and cell survival was analysed by plate count. Results showed that beside cells acclimated at lower ethanol concentration (6% v/v) became more susceptible to drying than nonacclimated ones, after rehydration they maintain their increased ability to grow in a synthetic wine. Acclimation at a higher ethanol concentration (10% v/v) produces several damages on the cell surface losing its ability to grow in a synthetic wine. In this work, we showed for the first time that sublethal alterations on bacterial surface induced by a pre-acclimation with a low ethanol concentration (6%), upon a freeze-drying process, result in a better bacterial adaptation to the stress conditions of wine-like medium, as well as to the preservation process. Understanding the adaptation to ethanol of oenological strains and their effects on the preservation process has a strong impact on winemaking process and allows to define the most appropriate conditions to obtain malolactic starters cultures. © 2015 The Society for Applied Microbiology.

Stress-Induced Enhancement of Ethanol Intake in C57BL/6J Mice with a History of Chronic Ethanol Exposure: Involvement of Kappa Opioid Receptors.

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Anderson, Rachel I; Lopez, Marcelo F; Becker, Howard C

2016-01-01

Our laboratory has previously demonstrated that daily forced swim stress (FSS) prior to ethanol drinking sessions facilitates enhanced ethanol consumption in mice with a history of chronic intermittent ethanol (CIE) vapor exposure without altering ethanol intake in air-exposed controls. Because both stress and chronic ethanol exposure have been shown to activate the dynorphin/kappa opioid receptor (KOR) system, the present study was designed to explore a potential role for KORs in modulating stress effects on ethanol consumption in the CIE model of dependence and relapse drinking. After stable baseline ethanol intake was established in adult male C57BL/6J mice, subjects received chronic intermittent exposure (16 h/day × 4 days/week) to ethanol vapor (CIE group) or air (CTL group). Weekly cycles of inhalation exposure were alternated with 5-day limited access drinking tests (1 h access to 15% ethanol). Experiment 1 compared effects of daily FSS and KOR activation on ethanol consumption. CIE and CTL mice were either exposed to FSS (10 min), the KOR agonist U50,488 (5 mg/kg), or a vehicle injection (non-stressed condition) prior to each daily drinking session during test weeks. FSS selectively increased drinking in CIE mice. U50,488 mimicked this effect in CIE mice, but also increased drinking in CTL mice. Experiment 2 assessed effects of KOR blockade on stress-induced drinking in CIE and CTL mice. Stressed and non-stressed mice were administered the short-acting KOR antagonist LY2444296 (0 or 5 mg/kg) 30 min prior to each drinking session during test weeks. FSS selectively increased ethanol consumption in CIE mice, an effect that was abolished by LY2444296 pretreatment. In Experiment 3, CIE and CTL mice were administered one of four doses of U50,488 (0, 1.25, 2.5, 5.0 mg/kg) 1 h prior to each daily drinking test (in lieu of FSS). All doses of U50,488 increased ethanol consumption in both CIE and CTL mice. The U50,488-induced increase in drinking was blocked by LY

Stress-induced enhancement of ethanol intake in C57BL/6J mice with a history of chronic ethanol exposure: Involvement of kappa opioid receptors

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Rachel Ivy Anderson

2016-02-01

Full Text Available Our laboratory has previously demonstrated that daily forced swim stress (FSS prior to ethanol drinking sessions facilitates enhanced ethanol consumption in mice with a history of chronic intermittent ethanol (CIE vapor exposure without altering ethanol intake in air-exposed controls. Because both stress and chronic ethanol exposure have been shown to activate the dynorphin/kappa opioid receptor (KOR system, the present study was designed to explore a potential role for KORs in modulating stress effects on ethanol consumption in the CIE model of dependence and relapse drinking. After stable baseline ethanol intake was established in adult male C57BL/6J mice, subjects received chronic intermittent exposure (16 hr/day x 4 days/week to ethanol vapor (CIE group or air (CTL group. Weekly cycles of inhalation exposure were alternated with 5-day limited access drinking tests (1 hour access to 15% ethanol. Experiment 1 compared effects of daily FSS and KOR activation on ethanol consumption. CIE and CTL mice were either exposed to FSS (10 min, the KOR agonist U50,488 (5 mg/kg, or a vehicle injection (non-stressed condition prior to each daily drinking session during test weeks. FSS selectively increased drinking in CIE mice. U50,488 mimicked this effect in CIE mice, but also increased drinking in CTL mice. Experiment 2 assessed effects of KOR blockade on stress-induced drinking in CIE and CTL mice. Stressed and non-stressed mice were administered the short-acting KOR antagonist LY2444296 (0 or 5 mg/kg 30 min prior to each drinking session during test weeks. FSS selectively increased ethanol consumption in CIE mice, an effect that was abolished by LY2444296 pretreatment. In Experiment 3, CIE and CTL mice were administered one of four doses of U50,488 (0,1.25, 2.5, 5.0 mg/kg one hour prior to each daily drinking test (in lieu of FSS. All doses of U50,488 increased ethanol consumption in both CIE and CTL mice. The U50,488-induced increase in drinking was

Ethanol-induced activation of adenine nucleotide turnover. Evidence for a role of acetate

International Nuclear Information System (INIS)

Puig, J.G.; Fox, I.H.

1984-01-01

Consumption of alcohol causes hyperuricemia by decreasing urate excretion and increasing its production. Our previous studies indicate that ethanol administration increases uric acid production by increasing ATP degradation to uric acid precursors. To test the hypothesis that ethanol-induced increased urate production results from acetate metabolism and enhanced adenosine triphosphate turnover, we gave intravenous sodium acetate, sodium chloride and ethanol (0.1 mmol/kg per min for 1 h) to five normal subjects. Acetate plasma levels increased from 0.04 +/- 0.01 mM (mean +/- SE) to peak values of 0.35 +/- 0.07 mM and to 0.08 +/- 0.01 mM during acetate and ethanol infusions, respectively. Urinary oxypurines increased to 223 +/- 13% and 316 +/- 44% of the base-line values during acetate and ethanol infusions, respectively. Urinary radioactivity from the adenine nucleotide pool labeled with [8-14C] adenine increased to 171 +/- 27% and to 128 +/- 8% of the base-line values after acetate and ethanol infusions. These data indicate that both ethanol and acetate increase purine nucleotide degradation by enhancing the turnover of the adenine nucleotide pool. They support the hypothesis that acetate metabolism contributes to the increased production of urate associated with ethanol intake

Hepatoprotective effect of leaves of aqueous ethanol extract of Cestrum nocturnum against paracetamol-induced hepatotoxicity

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M. Imran Qadir

2014-06-01

Full Text Available The hepatoprotective activities of Cestrum nocturnum (Queen of Night was evaluated against the paracetamol induced hepatotoxicity in the mice. Aqueous ethanol (30:70 extract of plant was obtained by maceration. Results showed that aqueous ethanol extract of C. nocturnum (250 mg/kg and 500 mg/kg produced significant (p<0.05 hepatoprotective activities against paracetamol induced liver injury in Swiss albino mice. Histopathalogical studied of liver further supported the hepatoprotective effects of C. notrunum. Phyto-chemical screening showed the presence of alkaloids, flavonoids, saponins, terpenes, phenolic compounds, carbohydrates and volatile oils. Most of the flavonoids have hepatoprotective activity. Therefore, the hepatoprotective activity of C. nocturnum may be due to the presence of flavonoids and phenolic components. It was concluded from the present study that aqueous ethanol extract of leaves of C. nocturnum has hepatoprotective activity against the paracetamol-induced hepatotoxicity in albino mice.

Mitochondrial ROS induced by chronic ethanol exposure promote hyper-activation of the NLRP3 inflammasome

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Laura R. Hoyt

2017-08-01

Full Text Available Alcohol use disorders are common both in the United States and globally, and are associated with a variety of co-morbid, inflammation-linked diseases. The pathogenesis of many of these ailments are driven by the activation of the NLRP3 inflammasome, a multi-protein intracellular pattern recognition receptor complex that facilitates the cleavage and secretion of the pro-inflammatory cytokines IL-1β and IL-18. We hypothesized that protracted exposure of leukocytes to ethanol would amplify inflammasome activation, which would help to implicate mechanisms involved in diseases associated with both alcoholism and aberrant NLRP3 inflammasome activation. Here we show that long-term ethanol exposure of human peripheral blood mononuclear cells and a mouse macrophage cell line (J774 amplifies IL-1β secretion following stimulation with NLRP3 agonists, but not with AIM2 or NLRP1b agonists. The augmented NRLP3 activation was mediated by increases in iNOS expression and NO production, in conjunction with increases in mitochondrial membrane depolarization, oxygen consumption rate, and ROS generation in J774 cells chronically exposed to ethanol (CE cells, effects that could be inhibited by the iNOS inhibitor SEITU, the NO scavenger carboxy-PTIO, and the mitochondrial ROS scavenger MitoQ. Chronic ethanol exposure did not alter K+ efflux or Zn2+ homeostasis in CE cells, although it did result in a lower intracellular concentration of NAD+. Prolonged administration of acetaldehyde, the product of alcohol dehydrogenase (ADH mediated metabolism of ethanol, mimicked chronic ethanol exposure, whereas ADH inhibition prevented ethanol-induced IL-1β hypersecretion. Together, these results indicate that increases in iNOS and mitochondrial ROS production are critical for chronic ethanol-induced IL-1β hypersecretion, and that protracted exposure to the products of ethanol metabolism are probable mediators of NLRP3 inflammasome hyperactivation. Keywords: Inflammasome, IL

Successful treatment of tumor-induced osteomalacia with CT-guided percutaneous ethanol and cryoablation.

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Tutton, Sean; Olson, Erik; King, David; Shaker, Joseph L

2012-10-01

Tumor-induced osteomalacia is a rare condition usually caused by benign mesenchymal tumors. When the tumor can be found, patients are usually managed by wide excision of the tumor. We report a 51-yr-old male with clinical and biochemical evidence of tumor-induced osteomalacia caused by a mesenchymal tumor in the right iliac bone. He declined surgery and appears to have been successfully managed by computed tomography-guided percutaneous ethanol ablation and percutaneous cryoablation. Our patient appears to have had an excellent clinical and biochemical response to computed tomography-guided percutaneous ethanol ablation and percutaneous cryoablation. We found one prior case of image-guided ablation using radiofrequency ablation for tumor-induced osteomalacia. Although the standard treatment for tumor-induced osteomalacia is wide excision of the tumor, image-guided ablation may be an option in patients who cannot have appropriate surgery or who decline surgery.

Ethanol induced antidepressant-like effect in the mouse forced swimming test: modulation by serotonergic system.

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Jain, Nishant S; Kannamwar, Uday; Verma, Lokesh

2017-02-01

The present investigation explored the modulatory role of serotonergic transmission in the acute ethanol-induced effects on immobility time in the mouse forced swim test (FST). Acute i.p. administration of ethanol (20% w/v, 2 or 2.5 g/kg, i.p.) decreased the immobility time in FST of mice, indicating its antidepressant-like effect while lower doses of ethanol (1, 1.5 g/kg, i.p.) were devoid of any effect in the FST. The mice pre-treated with a sub-effective dose of 5-HT 2A agonist, DOI (10 μg/mouse, i.c.v.) or 5-HT 1A receptor antagonist, WAY 100635 (0.1 μg/mouse, i.c.v.) but not with the 5-HT 2A/2C antagonist, ketanserin (1.5 μg/mouse, i.c.v.) exhibited a synergistic reduction in the immobility time induced by sub-effective dose of ethanol (1.5 g/kg, i.p.). On the other hand, ethanol (2.5 g/kg, i.p.) failed to decrease the immobility time in mice, pre-treated with 5-HT 1A agonist, 8-OH-DPAT (0.1 μg/mouse, i.c.v.) or ketanserin (1.5 μg/mouse, i.c.v.). In addition, pre-treatment with a 5-HT neuronal synthesis inhibitor, p-CPA (300 mg/kg, i.p. × 3 days) attenuated the anti-immobility effect ethanol (2.5 g/kg, i.p.) in mouse FST. Thus, the results of the present study points towards the essentiality of the central 5-HT transmission at the synapse for the ethanol-induced antidepressant-like effect in the FST wherein the regulatory role of the 5-HT 1A receptor or contributory role of the 5-HT 2A/2C receptor-mediated mechanism is proposed in the anti-immobility effect of acute ethanol in mouse FST.

The Protective Effect of Hydroalcoholic Extract of Zingiber officinale Roscoe (Ginger) on Ethanol-Induced Reproductive Toxicity in Male Rats.

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Akbari, Abolfazl; Nasiri, Khadijeh; Heydari, Mojtaba; Mosavat, Seyed Hamdollah; Iraji, Aida

2017-10-01

This study was conducted to evaluate the prophylactic effect of ginger extract on ethanol-induced reproductive toxicity in male rats. Twenty-eight adult male Sprague-Dawley rats were randomly divided into 4 groups and treated daily for 28 days as follows: control, control-ginger (1 g/kg of body weight [BW]/day by gavage), ethanol group (ethanol 4 g/kg of BW/day by gavage), and ginger-ethanol group. At the end of the experiment, all the rats were sacrificed and their testes were removed and used for measurement of the total homocysteine (tHcy), trace elements, antioxidant enzymes activity, and malondialdehyde (MDA). The results in the ethanol group indicate that ethanol decreased antioxidant enzymes activity and increased MDA and tHcy compared with the control groups ( P < .05). In ginger-ethanol group, ginger improved antioxidant enzymes activity and reduced tHcy and MDA compared to ethanol group ( P < .05). It can be concluded that ginger protects the ethanol-induced testicular damage and improves the hormonal levels, trace elements, antioxidant enzymes activity, and decreases tHcy and MDA.

Acute Ethanol Intake Induces NAD(P)H Oxidase Activation and Rhoa Translocation in Resistance Arteries.

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Simplicio, Janaina A; Hipólito, Ulisses Vilela; Vale, Gabriel Tavares do; Callera, Glaucia Elena; Pereira, Camila André; Touyz, Rhian M; Tostes, Rita de Cássia; Tirapelli, Carlos R

2016-11-01

The mechanism underlying the vascular dysfunction induced by ethanol is not totally understood. Identification of biochemical/molecular mechanisms that could explain such effects is warranted. To investigate whether acute ethanol intake activates the vascular RhoA/Rho kinase pathway in resistance arteries and the role of NAD(P)H oxidase-derived reactive oxygen species (ROS) on such response. We also evaluated the requirement of p47phox translocation for ethanol-induced NAD(P)H oxidase activation. Male Wistar rats were orally treated with ethanol (1g/kg, p.o. gavage) or water (control). Some rats were treated with vitamin C (250 mg/kg, p.o. gavage, 5 days) before administration of water or ethanol. The mesenteric arterial bed (MAB) was collected 30 min after ethanol administration. Vitamin C prevented ethanol-induced increase in superoxide anion (O2-) generation and lipoperoxidation in the MAB. Catalase and superoxide dismutase activities and the reduced glutathione, nitrate and hydrogen peroxide (H2O2) levels were not affected by ethanol. Vitamin C and 4-methylpyrazole prevented the increase on O2- generation induced by ethanol in cultured MAB vascular smooth muscle cells. Ethanol had no effect on phosphorylation levels of protein kinase B (Akt) and eNOS (Ser1177 or Thr495 residues) or MAB vascular reactivity. Vitamin C prevented ethanol-induced increase in the membrane: cytosol fraction ratio of p47phox and RhoA expression in the rat MAB. Acute ethanol intake induces activation of the RhoA/Rho kinase pathway by a mechanism that involves ROS generation. In resistance arteries, ethanol activates NAD(P)H oxidase by inducing p47phox translocation by a redox-sensitive mechanism. O mecanismo da disfunção vascular induzido pelo consumo de etanol não é totalmente compreendido. Justifica-se, assim a identificação de mecanismos bioquímicos e moleculares que poderiam explicar tais efeitos. Investigar se a ingestão aguda de etanol ativa a via vascular RhoA/Rho quinase

Differential contribution of complement receptor C5aR in myeloid and non-myeloid cells in chronic ethanol-induced liver injury in mice.

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McCullough, Rebecca L; McMullen, Megan R; Das, Dola; Roychowdhury, Sanjoy; Strainic, Michael G; Medof, M Edward; Nagy, Laura E

2016-07-01

Complement is implicated in the development of alcoholic liver disease. C3 and C5 contribute to ethanol-induced liver injury; however, the role of C5a receptor (C5aR) on myeloid and non-myeloid cells to progression of injury is not known. C57BL/6 (WT), global C5aR-/-, myeloid-specific C5aR-/-, and non-myeloid-specific C5aR-/- mice were fed a Lieber-DeCarli diet (32%kcal EtOH) for 25 days. Cultured hepatocytes were challenged with ethanol, TNFα, and C5a. Chronic ethanol feeding increased expression of pro-inflammatory mediators in livers of WT mice; this response was completely blunted in C5aR-/- mice. However, C5aR-/- mice were not protected from other measures of hepatocellular damage, including ethanol-induced increases in hepatic triglycerides, plasma alanine aminotransferase and hepatocyte apoptosis. CYP2E1 and 4-hydroxynonenal protein adducts were induced in WT and C5aR-/- mice. Myeloid-specific C5aR-/- mice were protected from ethanol-induced increases in hepatic TNFα, whereas non-myeloid-specific C5aR-/- displayed increased hepatocyte apoptosis and inflammation after chronic ethanol feeding. In cultured hepatocytes, cytotoxicity induced by challenge with ethanol and TNFα was completely eliminated by treatment with C5a in cells from WT, but not C5aR-/- mice. Further, treatment with C5a enhanced activation of pro-survival signal AKT in hepatocytes challenged with ethanol and TNFα. Taken together, these data reveal a differential role for C5aR during ethanol-induced liver inflammation and injury, with C5aR on myeloid cells contributing to ethanol-induced inflammatory cytokine expression, while non-myeloid C5aR protects hepatocytes from death after chronic ethanol feeding. Copyright © 2016 Elsevier Ltd. All rights reserved.

Possible mechanisms of action of Caesalpinia pyramidalis against ethanol-induced gastric damage.

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Diniz, Polyana B F; Ribeiro, Ana Roseli S; Estevam, Charles S; Bani, Cristiane C; Thomazzi, Sara M

2015-06-20

Caesalpinia pyramidalis Tul. (Fabaceae), known as "catingueira", is an endemic tree of the Northeast region of Brazil. This plant, mainly inner bark and flowers, has been used in traditional medicine to treat gastritis, heartburn, indigestion, stomachache, dysenteries, and diarrheas. The ethanol extract of C. pyramidalis inner bark was used in rats via oral route, at the doses of 30, 100, and 300 mg/kg, in the ethanol-induced ulcer model and some of the mechanisms underlying to the gastroprotective effect of this plant investigated. The ethanol extract of C. pyramidalis inner bark (100 mg/kg) produced reduction (P process with imbalance between pro-inflammatory and anti-inflammatory mediators, supporting the popular usage of this plant. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

A role for ethanol-induced oxidative stress in controlling lineage commitment of mesenchymal stromal cells through inhibition of wnt/beta-catenin signaling

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The mechanisms by which chronic ethanol intake induces bone loss remain unclear. In females, the skeletal response to ethanol varies depending on physiologic status (viz. cycling, pregnancy, lactation). Ethanol-induced oxidative stress appears to be a key event leading to skeletal toxicity. In the c...

Quetiapine mitigates the ethanol-induced oxidative stress in brain tissue, but not in the liver, of the rat

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Han JH

2015-06-01

Full Text Available Jin-hong Han,1,2 Hong-zhao Tian,2 Yang-yang Lian,1 Yi Yu,1 Cheng-biao Lu,2 Xin-min Li,3 Rui-ling Zhang,1 Haiyun Xu4 1The Second Affiliated Hospital of Xinxiang Medical University, 2School of Basic Medicine, Xinxiang Medical University, Xinxiang, Henan, People’s Republic of China; 3Department of Psychiatry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada; 4The Mental Health Center, Shantou University Medical College, Shantou, Guangdong, People’s Republic of China Abstract: Quetiapine, an atypical antipsychotic, has been employed to treat alcoholic patients with comorbid psychopathology. It was shown to scavenge hydroxyl radicals and to protect cultured cells from noxious effects of oxidative stress, a pathophysiological mechanism involved in the toxicity of alcohol. This study compared the redox status of the liver and the brain regions of prefrontal cortex, hippocampus, and cerebellum of rats treated with or without ethanol and quetiapine. Ethanol administration for 1 week induced oxidative stress in the liver and decreased the activity of glutathione peroxidase and total antioxidant capacity (TAC there. Coadministration of quetiapine did not protect glutathione peroxidase and TAC in the liver against the noxious effect of ethanol, thus was unable to mitigate the ethanol-induced oxidative stress there. The ethanol-induced alteration in the redox status in the prefrontal cortex is mild, whereas the hippocampus and cerebellum are more susceptible to ethanol intoxication. For all the examined brain regions, coadministration of quetiapine exerted effective protection on the antioxidants catalase and total superoxide dismutase and on the TAC, thus completely blocking the ethanol-induced oxidative stress in these brain regions. These protective effects may explain the clinical observations that quetiapine reduced psychiatric symptoms intensity and maintained a good level of tolerability in chronic alcoholism with

Impaired TFEB-mediated Lysosome Biogenesis and Autophagy Promote Chronic Ethanol-induced Liver Injury and Steatosis in Mice.

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Chao, Xiaojuan; Wang, Shaogui; Zhao, Katrina; Li, Yuan; Williams, Jessica A; Li, Tiangang; Chavan, Hemantkumar; Krishnamurthy, Partha; He, Xi C; Li, Linheng; Ballabio, Andrea; Ni, Hong-Min; Ding, Wen-Xing

2018-05-18

Defects in lysosome function and autophagy contribute to pathogenesis of alcoholic liver disease. We investigated the mechanisms by which alcohol consumption affects these processes, evaluating the functions transcription factor EB (TFEB), which regulates lysosomal biogenesis. We performed studies with GFP-LC3 mice, mice with liver-specific deletion of transcription factor EB (TFEB), mice with disruption of the transcription factor E3 gene (TFE3-knockout mice), mice with disruption of the Tefb and Tfe3 genes (TFEB, TFE3 double-knockout mice), and Tfeb flox/flox albumin cre-negative mice (controls). TFEB was overexpressed from adenoviral vectors or knocked down with small interfering RNAs in mouse livers. Mice were placed on diets of chronic ethanol feeding plus an acute binge to induce liver damage (ethanol diet); some mice were also given injections of torin1, an inhibitor of the kinase activity of the mechanistic target of rapamycin (mTOR). Liver tissues were collected and analyzed by immunohistochemistry, immunoblots, and quantitative real-time PCR to monitor lysosome biogenesis. We analyzed levels of TFEB in liver tissues from patients with alcoholic hepatitis and from healthy donors (controls) by immunohistochemistry. Liver tissues from mice on the ethanol diet had lower levels of total and nuclear TFEB, compared with control mice, and hepatocytes had reduced lysosome biogenesis and autophagy. Hepatocytes from mice on the ethanol diet had increased translocation of mTOR into lysosomes, resulting increased mTOR activation. Administration of torin1 increased liver levels of TFEB and reduced steatosis and liver injury induced by ethanol. Mice that overexpressed TFEB in liver developed less-severe ethanol-induced liver injury and had increased lysosomal biogenesis and mitochondrial bioenergetics compared to mice carrying a control vector. Mice with knockdown of TFEB, as well as TFEB, TFE3 double-knockout mice, developed more severe liver injury in response to the

Ecklonia cava Polyphenol Has a Protective Effect against Ethanol-Induced Liver Injury in a Cyclic AMP-Dependent Manner

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Haruka Yamashita

2015-06-01

Full Text Available Previously, we showed that Ecklonia cava polyphenol (ECP treatment suppressed ethanol-induced increases in hepatocyte death by scavenging intracellular reactive oxygen species (ROS and maintaining intracellular glutathione levels. Here, we examined the effects of ECP on the activities of alcohol-metabolizing enzymes and their regulating mechanisms in ethanol-treated hepatocytes. Isolated hepatocytes were incubated with or without 100 mM ethanol. ECP was dissolved in dimethylsulfoxide. ECP was added to cultured cells that had been incubated with or without ethanol. The cells were incubated for 0–24 h. In cultured hepatocytes, the ECP treatment with ethanol inhibited cytochrome P450 2E1 (CYP2E1 expression and activity, which is related to the production of ROS when large quantities of ethanol are oxidized. On the other hand, ECP treatment with ethanol increased the activity of alcohol dehydrogenase (ADH and aldehyde dehydrogenase. These changes in activities of CYP2E1 and ADH were suppressed by treatment with H89, an inhibitor of protein kinase A. ECP treatment with ethanol enhanced cyclic AMP concentrations compared with those of control cells. ECP may be a candidate for preventing ethanol-induced liver injury via regulating alcohol metabolic enzymes in a cyclic AMP-dependent manner.

Paternal preconception ethanol exposure blunts hypothalamic-pituitary-adrenal axis responsivity and stress-induced excessive fluid intake in male mice.

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Rompala, Gregory R; Finegersh, Andrey; Homanics, Gregg E

2016-06-01

A growing number of environmental insults have been shown to induce epigenetic effects that persist across generations. For instance, paternal preconception exposures to ethanol or stress have independently been shown to exert such intergenerational effects. Since ethanol exposure is a physiological stressor that activates the hypothalamic-pituitary-adrenal (HPA) axis, we hypothesized that paternal ethanol exposure would impact stress responsivity of offspring. Adult male mice were exposed to chronic intermittent vapor ethanol or control conditions for 5 weeks before being mated with ethanol-naïve females to produce ethanol (E)- and control (C)-sired offspring. Adult male and female offspring were tested for plasma corticosterone (CORT) levels following acute restraint stress and the male offspring were further examined for stress-evoked 2-bottle choice ethanol-drinking. Paternal ethanol exposure blunted plasma CORT levels following acute restraint stress selectively in male offspring; females were unaffected. In a stress-evoked ethanol-drinking assay, there was no effect of stress on ethanol consumption. However, C-sired males exhibited increased total fluid intake (polydipsia) in response to stress while E-sired males were resistant to this stress-induced phenotype. Taken together, these data suggest that paternal ethanol exposure imparts stress hyporesponsivity to male offspring. Copyright © 2016 Elsevier Inc. All rights reserved.

Administration of memantine during ethanol withdrawal in neonatal rats: effects on long-term ethanol-induced motor incoordination and cerebellar Purkinje cell loss.

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Idrus, Nirelia M; McGough, Nancy N H; Riley, Edward P; Thomas, Jennifer D

2011-02-01

Alcohol consumption during pregnancy can damage the developing fetus, illustrated by central nervous system dysfunction and deficits in motor and cognitive abilities. Binge drinking has been associated with an increased risk of fetal alcohol spectrum disorders, likely due to increased episodes of ethanol withdrawal. We hypothesized that overactivity of the N-methyl-D-aspartate (NMDA) receptor during ethanol withdrawal leads to excitotoxic cell death in the developing brain. Consistent with this, administration of NMDA receptor antagonists (e.g., MK-801) during withdrawal can attenuate ethanol's teratogenic effects. The aim of this study was to determine whether administration of memantine, an NMDA receptor antagonist, during ethanol withdrawal could effectively attenuate ethanol-related deficits, without the adverse side effects associated with other NMDA receptor antagonists. Sprague-Dawley pups were exposed to 6.0 g/kg ethanol or isocaloric maltose solution via intubation on postnatal day 6, a period of brain development equivalent to a portion of the 3rd trimester. Twenty-four and 36 hours after ethanol, subjects were injected with 0, 10, or 15 mg/kg memantine, totaling doses of 0, 20, or 30 mg/kg. Motor coordination was tested on a parallel bar task and the total number of cerebellar Purkinje cells was estimated using unbiased stereology. Alcohol exposure induced significant parallel bar motor incoordination and reduced Purkinje cell number. Memantine administration significantly attenuated both ethanol-associated motor deficits and cerebellar cell loss in a dose-dependent manner. Memantine was neuroprotective when administered during ethanol withdrawal. These data provide further support that ethanol withdrawal contributes to fetal alcohol spectrum disorders. Copyright © 2010 by the Research Society on Alcoholism.

Heavy Chronic Ethanol Exposure From Adolescence to Adulthood Induces Cerebellar Neuronal Loss and Motor Function Damage in Female Rats

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Fernando B. R. da Silva

2018-05-01

Full Text Available Over the last years, heavy ethanol consumption by teenagers/younger adults has increased considerably among females. However, few studies have addressed the long-term impact on brain structures’ morphology and function of chronic exposure to high ethanol doses from adolescence to adulthood in females. In line with this idea, in the current study we investigated whether heavy chronic ethanol exposure during adolescence to adulthood may induce motor impairments and morphological and cellular alterations in the cerebellum of female rats. Adolescent female Wistar rats (35 days old were treated with distilled water or ethanol (6.5 g/kg/day, 22.5% w/v during 55 days by gavage. At 90 days of age, motor function of animals was assessed using open field (OF, pole, beam walking and rotarod tests. Following completion of behavioral tests, morphological and immunohistochemical analyses of the cerebellum were performed. Chronic ethanol exposure impaired significantly motor performance of female rats, inducing spontaneous locomotor activity deficits, bradykinesia, incoordination and motor learning disruption. Moreover, histological analysis revealed that ethanol exposure induced atrophy and neuronal loss in the cerebellum. These findings indicate that heavy ethanol exposure during adolescence is associated with long-lasting cerebellar degeneration and motor impairments in female rats.

Mitigation of postnatal ethanol-induced neuroinflammation ameliorates trace fear memory deficits in juvenile rats.

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Goodfellow, Molly J; Shin, Youn Ju; Lindquist, Derick H

2018-02-15

Impairments in behavior and cognition are common in individuals diagnosed with fetal alcohol spectrum disorders (FASD). In this study, FASD model rats were intragastrically intubated with ethanol (5g/kg/day; 5E), sham-intubated (SI), or maintained as naïve controls (NC) over postnatal days (PD) 4-9. Ethanol exposure during this human third trimester-equivalent period induces persistent impairments in hippocampus-dependent learning and memory. The ability of ibuprofen (IBU), a non-steroidal anti-inflammatory drug, to diminish ethanol-induced neuroinflammation and rescue deficits in hippocampus-dependent trace fear conditioning (TFC) was investigated in 5E rats. Phosphate buffered saline vehicle (VEH) or IBU was injected 2h following ethanol exposure over PD4-9, followed by quantification of inflammation-related genes in the dorsal hippocampus of PD10 rats. The 5E-VEH rats exhibited significant increases in Il1b and Tnf, but not Itgam or Gfap, relative to NC, SI-VEH, and 5E-IBU rats. In separate groups of PD31-33 rats, conditioned fear (freezing) was significantly reduced in 5E-VEH rats during TFC testing, but not acquisition, compared to SI-VEH and, critically, 5E-IBU rats. Results suggest neuroimmune activation in response to ethanol within the neonate hippocampus contributes to later-life cognitive dysfunction. Copyright © 2017 Elsevier B.V. All rights reserved.

Value Chain Structures that Define European Cellulosic Ethanol Production

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Jay Sterling Gregg

2017-01-01

Full Text Available Production of cellulosic ethanol (CE has not yet reached the scale envisaged by the literature and industry. This study explores CE production in Europe to improve understanding of the motivations and barriers associated with this situation. To do this, we conduct a case study-based analysis of CE production plants across Europe from a global value chain (GVC perspective. We find that most CE production plants in the EU focus largely on intellectual property and are therefore only at the pilot or demonstration scale. Crescentino, the largest CE production facility in Europe, is also more interested in technology licensing than producing ethanol. Demonstration-scale plants tend to have a larger variety of feedstocks, whereas forestry-based plants have more diversity of outputs. As scale increases, the diversity of feedstocks and outputs diminishes, and firms struggle with feedstock provisioning, global petroleum markets and higher financial risks. We argue that, to increase CE production, policies should consider value chains, promote the wider bio-economy of products and focus on economies of scope. Whereas the EU and its member states have ethanol quotas and blending targets, a more effective policy would be to seek to reduce the risks involved in financing capital projects, secure feedstock provisioning and support a diversity of end products.

Hepato- and neuro-protective effects of watermelon juice on acute ethanol-induced oxidative stress in rats

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Omolola R. Oyenihi

Full Text Available Chronic and acute alcohol exposure has been extensively reported to cause oxidative stress in hepatic and extra-hepatic tissues. Watermelon (Citrullus lanatus is known to possess various beneficial properties including; antioxidant, anti-inflammatory, analgesic, anti-diabetic, anti-ulcerogenic effects. However, there is a lack of pertinent information on its importance in acute alcohol-induced hepato- and neuro-toxicity. The present study evaluated the potential protective effects of watermelon juice on ethanol-induced oxidative stress in the liver and brain of male Wistar rats. Rats were pre-treated with the watermelon juice at a dose of 4 ml/kg body weight for a period of fifteen days prior to a single dose of ethanol (50%; 12 ml/kg body weight. Ethanol treatment reduced body weight gain and significantly altered antioxidant status in the liver and brain. This is evidenced by the significant elevation of malondialdehyde (MDA concentration; depletion in reduced glutathione (GSH levels and an increased catalase (CAT activity in the brain and liver. There was no significant difference in the activity of glutathione peroxidase (GPX in the liver and brain.Oral administration of watermelon juice for fifteen (15 days prior to ethanol intoxication, significantly reduced the concentration of MDA in the liver and brain of rats. In addition, water melon pre-treatment increased the concentration of GSH and normalized catalase activity in both tissues in comparison to the ethanol control group. Phytochemical analysis revealed the presence of phenol, alkaloids, saponins, tannins and steroids in watermelon juice. Our findings indicate that watermelon juice demonstrate anti-oxidative effects in ethanol-induced oxidation in the liver and brain of rats; which could be associated with the plethora of antioxidant phyto-constituents present there-in. Keywords: Watermelon, Neuro-protective, Hepatoprotective, Ethanol intoxication

Alpha7 nicotinic receptor mediated protection against ethanol-induced cytotoxicity in PC12 cells.

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Li, Y; King, M A; Grimes, J; Smith, N; de Fiebre, C M; Meyer, E M

1999-01-16

Ethanol caused a concentration-dependent loss of PC12 cells over a 24 h interval, accompanied by an increase in intracellular calcium. The specific alpha7 nicotinic receptor partial agonist DMXB attenuated both of these ethanol-induced actions at a concentration (3 microM) found previously to protect against apoptotic and necrotic cell loss. The alpha7 nicotinic receptor antagonist methylylaconitine blocked the neuroprotective action of DMXB when applied with but not 30 min after the agonist. These results indicate that activation of alpha7 nicotinic receptors may be therapeutically useful in preventing ethanol-neurotoxicity. Copyright 1999 Elsevier Science B.V.

Vanillin abrogates ethanol induced gastric injury in rats via modulation of gastric secretion, oxidative stress and inflammation

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Abdulrahman Al Asmari

Full Text Available Vanillin is commonly used as an additive in food, medicine and cosmetics, but its effect has not yet been studied in gastric injury. Therefore the effect of vanillin was studied in experimental gastric ulcer. Gastric secretion and acidity were studied in pylorus ligated rats. Ulcer index, levels of gastric mucus, malondialdehyde (MDA, myeloperoxidase activity (MPO, expression of nuclear factor kappa B (NF-κB p65, and histopathological changes were determined in ethanol induced gastric ulcer. Pre treatment with vanillin significantly reduced gastric secretion (P < 0.001 and acidity (P < 0.0001 and gastric ulcer index scores (P < 0.001. and augmented the gastric mucosal defense. Vanillin significantly restored the depleted gastric wall mucus levels (P < 0.0001 induced by ethanol and also significantly attenuated ethanol induced inflammation and oxidative stress by the suppression of gastric MPO activity (P < 0.001, reducing the expression of NF-κB p65 and the increased MDA levels (P < 0.001. Vanillin was also effective in alleviating the damage to the histological architecture and the activation of mast cells induced by ethanol.Together the results of this study highlight the gastroprotective activity of vanillin in gastric ulcers of rats through multiple actions that include inhibition of gastric secretion and acidity, reduction of inflammation and oxidative stress, suppression of expression of NF-κB, and restoration of the histological architecture. Keywords: Gastric ulcers, Pylorus ligation, Ethanol, Vanillin, Inflammation, Oxidative stress

Impairment of Akt activity by CYP2E1 mediated oxidative stress is involved in chronic ethanol-induced fatty liver

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Tao Zeng

2018-04-01

Full Text Available Protein kinase B (PKB/Akt plays important roles in the regulation of lipid homeostasis, and impairment of Akt activity has been demonstrated to be involved in the development of non-alcoholic fatty liver disease (NAFLD. Previous studies suggest that cytochrome P4502E1 (CYP2E1 plays causal roles in the pathogenesis of alcoholic fatty liver (AFL. We hypothesized that Akt activity might be impaired due to CYP2E1-induced oxidative stress in chronic ethanol-induced hepatic steatosis. In this study, we found that chronic ethanol-induced hepatic steatosis was accompanied with reduced phosphorylation of Akt at Thr308 in mice liver. Chronic ethanol exposure had no effects on the protein levels of phosphatidylinositol 3 kinase (PI3K and phosphatase and tensin homologue deleted on chromosome ten (PTEN, and led to a slight decrease of phosphoinositide-dependent protein kinase 1 (PDK-1 protein level. Ethanol exposure resulted in increased levels of malondialdehyde (MDA and 4-hydroxynonenal (4-HNE-Akt adducts, which was significantly inhibited by chlormethiazole (CMZ, an efficient CYP2E1 inhibitor. Interestingly, N-acetyl-L-cysteine (NAC significantly attenuated chronic ethanol-induced hepatic fat accumulation and the decline of Akt phosphorylation at Thr308. In the in vitro studies, Akt phosphorylation was suppressed in CYP2E1-expressing HepG2 (CYP2E1-HepG2 cells compared with the negative control HepG2 (NC-HepG2 cells, and 4-HNE treatment led to significant decrease of Akt phosphorylation at Thr308 in wild type HepG2 cells. Lastly, pharmacological activation of Akt by insulin-like growth factor-1 (IGF-1 significantly alleviated chronic ethanol-induced fatty liver in mice. Collectively, these results indicate that CYP2E1-induced oxidative stress may be responsible for ethanol-induced suppression of Akt phosphorylation and pharmacological modulation of Akt in liver may be an effective strategy for the treatment of ethanol-induced fatty liver. Keywords

Social opportunity and ethanol drinking in rats.

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Tomie, Arthur; Burger, Kelly M; Di Poce, Jason; Pohorecky, Larissa A

2004-11-01

Two experiments were designed to evaluate the effects of pairings of ethanol sipper conditioned stimulus (CS) with social opportunity unconditioned stimulus (US) on ethanol sipper CS-directed drinking in rats. In both experiments, rats were deprived of neither food nor water, and initiation of drinking of unsweetened 3% ethanol was evaluated, as were the effects of increasing the concentration of unsweetened ethanol (3-10%) across sessions. In Experiment 1, Group Paired (n=8) received 35 trials per session wherein the ethanol sipper CS was presented for 10 s immediately prior to 15 s of social opportunity US. All rats initiated sipper CS-directed drinking of 3% ethanol. Increasing the concentration of ethanol in the sipper CS [(3%, 4%, 6%, 8%, 10% (vol./vol.)] across sessions induced escalation of daily g/kg ethanol intake. To evaluate the hypothesis that the drinking in Group Paired was due to autoshaping, Experiment 2 included a pseudoconditioning control that received sipper CS and social opportunity US randomly with respect to one another. All rats in Group Paired (n=6) and in Group Random (n=6) initiated sipper CS-directed drinking of 3% ethanol and daily mean g/kg ethanol intake in the two groups was comparable. Also comparable was daily g/kg ethanol intake, which increased for both groups with the availability of higher concentrations of ethanol in the sipper CS, up to a maximum of approximately 0.8 g/kg ethanol intake of 10% ethanol. Results indicate that random presentations of ethanol sipper CS and social opportunity US induced reliable initiation and escalation of ethanol intake, and close temporally contiguous presentations of CS and US did not induce still additional ethanol intake. This may indicate that autoshaping CR performance is not induced by these procedures, or that high levels of ethanol intake induced by factors related to pseudoconditioning produces a ceiling effect. Implications for ethanol drinking in humans are discussed.

Hepatoprotective potential of Lavandula coronopifolia extracts against ethanol induced oxidative stress-mediated cytotoxicity in HepG2 cells.

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Farshori, Nida Nayyar; Al-Sheddi, Ebtsam S; Al-Oqail, Mai M; Hassan, Wafaa H B; Al-Khedhairy, Abdulaziz A; Musarrat, Javed; Siddiqui, Maqsood A

2015-08-01

The present investigations were carried out to study the protective potential of four extracts (namely petroleum ether extract (LCR), chloroform extract (LCM), ethyl acetate extract (LCE), and alcoholic extract (LCL)) of Lavandula coronopifolia on oxidative stress-mediated cell death induced by ethanol, a known hepatotoxin in human hapatocellular carcinoma (HepG2) cells. Cells were pretreated with LCR, LCM, LCE, and LCL extracts (10-50 μg/ml) of L. coronopifolia for 24 h and then ethanol was added and incubated further for 24 h. After the exposure, cell viability using (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and neutral red uptake assays and morphological changes in HepG2 cells were studied. Pretreatment with various extracts of L. coronpifolia was found to be significantly effective in countering the cytotoxic responses of ethanol. Antioxidant properties of these L. coronopifolia extracts against reactive oxygen species (ROS) generation, lipid peroxidation (LPO), and glutathione (GSH) levels induced by ethanol were investigated. Results show that pretreatment with these extracts for 24 h significantly inhibited ROS generation and LPO induced and increased the GSH levels reduced by ethanol. The data from the study suggests that LCR, LCM, LCE, and LCL extracts of L. coronopifolia showed hepatoprotective activity against ethanol-induced damage in HepG2 cells. However, a comparative study revealed that the LCE extract was found to be the most effective and LCL the least effective. The hepatoprotective effects observed in the study could be associated with the antioxidant properties of these extracts of L. coronopifolia. © The Author(s) 2013.

Metabolic basis of ethanol-induced cytotoxicity in recombinant HepG2 cells: Role of nonoxidative metabolism

International Nuclear Information System (INIS)

Wu Hai; Cai Ping; Clemens, Dahn L.; Jerrells, Thomas R.; Ansari, G.A. Shakeel; Kaphalia, Bhupendra S.

2006-01-01

Chronic alcohol abuse, a major health problem, causes liver and pancreatic diseases and is known to impair hepatic alcohol dehydrogenase (ADH). Hepatic ADH-catalyzed oxidation of ethanol is a major pathway for the ethanol disposition in the body. Hepatic microsomal cytochrome P450 (CYP2E1), induced in chronic alcohol abuse, is also reported to oxidize ethanol. However, impaired hepatic ADH activity in a rat model is known to facilitate a nonoxidative metabolism resulting in formation of nonoxidative metabolites of ethanol such as fatty acid ethyl esters (FAEEs) via a nonoxidative pathway catalyzed by FAEE synthase. Therefore, the metabolic basis of ethanol-induced cytotoxicity was determined in HepG2 cells and recombinant HepG2 cells transfected with ADH (VA-13), CYP2E1 (E47) or ADH + CYP2E1 (VL-17A). Western blot analysis shows ADH deficiency in HepG2 and E47 cells, compared to ADH-overexpressed VA-13 and VL-17A cells. Attached HepG2 cells and the recombinant cells were incubated with ethanol, and nonoxidative metabolism of ethanol was determined by measuring the formation of FAEEs. Significantly higher levels of FAEEs were synthesized in HepG2 and E47 cells than in VA-13 and VL-17A cells at all concentrations of ethanol (100-800 mg%) incubated for 6 h (optimal time for the synthesis of FAEEs) in cell culture. These results suggest that ADH-catalyzed oxidative metabolism of ethanol is the major mechanism of its disposition, regardless of CYP2E1 overexpression. On the other hand, diminished ADH activity facilitates nonoxidative metabolism of ethanol to FAEEs as found in E47 cells, regardless of CYP2E1 overexpression. Therefore, CYP2E1-mediated oxidation of ethanol could be a minor mechanism of ethanol disposition. Further studies conducted only in HepG2 and VA-13 cells showed lower ethanol disposition and ATP concentration and higher accumulation of neutral lipids and cytotoxicity (apoptosis) in HepG2 cells than in VA-13 cells. The apoptosis observed in HepG2 vs

Gastroprotective effect of Cymbopogon citratus infusion on acute ethanol-induced gastric lesions in rats.

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Sagradas, Joana; Costa, Gustavo; Figueirinha, Artur; Castel-Branco, Maria Margarida; Silvério Cabrita, António Manuel; Figueiredo, Isabel Vitória; Batista, Maria Teresa

2015-09-15

Treatment of gastric ulcers with medicinal plants is quite common in traditional medicine worldwide. Cymbopogon citratus (DC) Stapf. leaves infusion has been used in folk medicine of many tropical and subtropical regions to treat gastric disturbances. The aim of this study was to assess the potential gastroprotective activity of an essential oil-free infusion from C. citratus leaves in acute gastric lesions induced by ethanol in rat. The study was performed on adult male Wistar rats (234.0±22.7g) fasted for 24h but with free access to water. The extract was given orally before (prevention) or after (treatment) intragastric administration of absolute ethanol. Effects of dose (28 or 56mg/kg of body weight) and time of contact of the extract with gastric mucosa (1 or 2h) were also assessed. Animals were sacrificed, being the stomachs removed and the lesions were assessed by macroscopic observation and histopathology. C. citratus extract, given orally before or after ethanol, significantly (P<0.01) reduced gastric mucosal injury compared with control group (vehicle+ethanol). The effect does not appear to be dose-dependent. Results also suggested that the extract is more effective when the time of contact with gastric mucosa increases. The results of this assay confirm the gastroprotective activity of C. citratus extract on experimental gastric lesions induced by ethanol, contributing for the pharmacological validation of its traditional use. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Carbon Monoxide (CO Released from Tricarbonyldichlororuthenium (II Dimer (CORM-2 in Gastroprotection against Experimental Ethanol-Induced Gastric Damage.

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Katarzyna Magierowska

Full Text Available The physiological gaseous molecule, carbon monoxide (CO becomes a subject of extensive investigation due to its vasoactive activity throughout the body but its role in gastroprotection has been little investigated. We determined the mechanism of CO released from its donor tricarbonyldichlororuthenium (II dimer (CORM-2 in protection of gastric mucosa against 75% ethanol-induced injury. Rats were pretreated with CORM-2 30 min prior to 75% ethanol with or without 1 non-selective (indomethacin or selective cyclooxygenase (COX-1 (SC-560 and COX-2 (celecoxib inhibitors, 2 nitric oxide (NO synthase inhibitor L-NNA, 3 ODQ, a soluble guanylyl cyclase (sGC inhibitor, hemin, a heme oxygenase (HO-1 inductor or zinc protoporphyrin IX (ZnPPIX, an inhibitor of HO-1 activity. The CO content in gastric mucosa and carboxyhemoglobin (COHb level in blood was analyzed by gas chromatography. The gastric mucosal mRNA expression for HO-1, COX-1, COX-2, iNOS, IL-4, IL-1β was analyzed by real-time PCR while HO-1, HO-2 and Nrf2 protein expression was determined by Western Blot. Pretreatment with CORM-2 (0.5-10 mg/kg dose-dependently attenuated ethanol-induced lesions and raised gastric blood flow (GBF but large dose of 100 mg/kg was ineffective. CORM-2 (5 mg/kg and 50 mg/kg i.g. significantly increased gastric mucosal CO content and whole blood COHb level. CORM-2-induced protection was reversed by indomethacin, SC-560 and significantly attenuated by celecoxib, ODQ and L-NNA. Hemin significantly reduced ethanol damage and raised GBF while ZnPPIX which exacerbated ethanol-induced injury inhibited CORM-2- and hemin-induced gastroprotection and the accompanying rise in GBF. CORM-2 significantly increased gastric mucosal HO-1 mRNA expression and decreased mRNA expression for iNOS, IL-1β, COX-1 and COX-2 but failed to affect HO-1 and Nrf2 protein expression decreased by ethanol. We conclude that CORM-2 released CO exerts gastroprotection against ethanol-induced gastric

Cholera toxin-induced ADP-ribosylation of a 46 kDa protein is decreased in brains of ethanol-fed mice

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Nhamburo, P.T.; Hoffman, P.L.; Tabakoff, B.

1988-01-01

The acute in vitro effects of ethanol on cerebral cortical adenylate cyclase activity and beta-adrenergic receptor characteristics suggested a site of action of ethanol at Gs, the stimulatory guanine nucleotide binding protein. After chronic ethanol ingestion, the beta-adrenergic receptor appeared to be uncoupled (i.e., the form of the receptor with high affinity for agonist was undetectable), and stimulation of adenylate cyclase activity by isoproterenol or guanine nucleotides was reduced, suggesting an alteration in the properties of Gs. To further characterize this change, cholera and pertussis toxin-mediated 32 P-ADP-ribosylation of mouse cortical membranes was assessed in mice that had chronically ingested ethanol in a liquid diet. 32 P-labeled proteins were separated by SDS-PAGE and quantitated by autoradiography. There was a selective 30-50% decrease in cholera toxin-induced labeling of 46 kDa protein band in membranes of ethanol-fed mice, with no apparent change in pertussis toxin-induced labeling. The 46 kDa protein has a molecular weight similar to that of the alpha subunit of Gs, suggesting a reduced amount of this protein or a change in its characteristics as a substrate for cholera toxin-induced ADP-ribosylation in cortical membranes of ethanol-fed mice

Silencing of cytosolic NADP+-dependent isocitrate dehydrogenase gene enhances ethanol-induced toxicity in HepG2 cells.

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Yang, Eun Sun; Lee, Su-Min; Park, Jeen-Woo

2010-07-01

It has been shown that acute and chronic alcohol administrations increase the production of reactive oxygen species, lower cellular antioxidant levels and enhance oxidative stress in many tissues. We recently reported that cytosolic NADP(+)-dependent isocitrate dehydrogenase (IDPc) functions as an antioxidant enzyme by supplying NADPH to the cytosol. Upon exposure to ethanol, IDPc was susceptible to the loss of its enzyme activity in HepG2 cells. Transfection of HepG2 cells with an IDPc small interfering RNA noticeably downregulated IDPc and enhanced the cells' vulnerability to ethanol-induced cytotoxicity. Our results suggest that suppressing the expression of IDPc enhances ethanol-induced toxicity in HepG2 cells by further disruption of the cellular redox status.

Ligno-ethanol in competition with food-based ethanol in Germany

International Nuclear Information System (INIS)

Poganietz, Witold-Roger

2012-01-01

First-generation biofuels are often challenged over their potentially adverse impact on food prices. Biofuels that use nonfood biomass such as lignocellulose are being promoted to ease the conflict between fuels and food. However, their complex processes mean that the total costs of lignocellulosic ethanol may be high in comparison. This might undermine the economic soundness of plans for its use. Another potential advantage of lignocellulosic ethanol is seen in an enhanced contribution to a reduction in greenhouse gas emissions. Yet the increasing attractiveness of lignocellulosic biofuels may also lead to changes in land use that induce additional carbon emissions. For this reason, the environmental impacts of such plans are not straightforward and depend on the affected category of land. The objective of this paper is to compare the economic perspectives and environmental impact of lignocellulosic ethanol with food-based ethanol taking into account market constraints and policy measures. The analysis of the environmental impact focuses on carbon dioxide emissions. In the medium run, i.e., by 2020, lignocellulosic ethanol could enter the gasoline market, crowding out inter alia food-based ethanol. In terms of carbon dioxide emissions, lignocellulosic ethanol seems to be environmentally desirable in each of the analyzed cases. The findings depend crucially on the market conditions, which are influenced inter alia by crude oil, the exchange rate, and technology conditions. -- Highlights: ► Competition of ligno-ethanol with competing energy carriers is analyzed. ► In medium-term ligno-ethanol could crowd out food-based ethanol. ► In terms of CO 2 ligno-ethanol seems to be environmentally desirable. ► The environmental impacts include by land use change induced CO 2 emissions. ► The findings depend crucially on market conditions.

Induced synthesis of toroid-like lead sulfide nanocomposites in ethanol solution through a protein templating route

International Nuclear Information System (INIS)

Zhang, Li; Qin, Dezhi; Yang, Guangrui; Du, Xian; Zhang, Qiuxia; Li, Feng

2015-01-01

The toroid-like PbS nanocrystals have been prepared in zein ethanol solution based on self-assembly template of protein molecules. From transmission electron microscopy observation, the obtained samples were monodispersed with an average size of about 47 nm. The chemical composition and crystal structure of nanocomposites were determined by X-ray diffraction and energy-dispersive X-ray spectrum measurements. The interaction between PbS and zein was investigated through Fourier transform infrared, photoluminescence, circular dichroism (CD) spectra, and thermogravimetric analysis. The PbS nanocrystals could react with nitrogen and oxygen atoms of zein molecules through coordination and electrostatic force. The CD spectra results suggested that PbS nanocrystals induced the conformational transition of protein from α-helix to β-sheet and then self-assembled into ring or toroid nanostructure. The quenching of zein fluorescence induced by PbS nanocrystals also showed the change in the chemical microenvironments of the fluorescent amino acid residues in the protein structure. The key step of this facile, biomimetic route was the formation of self-assembly nanostructure of zein, which could regulate the nucleation and growth of toroid-like PbS nanocrystals

Ameliorative Activity of Ethanolic Extract of Artocarpus heterophyllus Stem Bark on Alloxan-induced Diabetic Rats

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Basiru Olaitan Ajiboye

2018-03-01

Full Text Available Purpose: Diabetes mellitus is one of the major endocrine disorders, characterized by impaired insulin action and deficiency. Traditionally, Artocarpus heterophyllus stem bark has been reputably used in the management of diabetes mellitus and its complications. The present study evaluates the ameliorative activity of ethanol extract of Artocarpus heterophyllus stem bark in alloxan-induced diabetic rats. Methods: Diabetes mellitus was induced by single intraperitoneal injection of 150 mg/kg body weight of alloxan and the animals were orally administered with 50, 100 and 150 mg/kg body weight ethanol extract of Artocarpus heterophyllus stem bark once daily for 21 days. Results: At the end of the intervention, diabetic control rats showed significant (p0.05 different with non-diabetic rats. Conclusion: The results suggest that ethanol extract of Artocarpus heterophyllus stem bark may be useful in ameliorating complications associated with diabetes mellitus patients.

Pairings of ethanol sipper with food induces Pavlovian autoshaping of ethanol drinking in rats: evidence of long-term retention and effects of sipper duration.

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Tomie, Arthur; Sparta, Dennis R; Silberman, Yuval; Interlandi, Jeneen; Mynko, Alise; Patterson-Buckendahl, Patricia; Pohorecky, Larissa A

2002-01-01

This study asks if repeated Pavlovian pairings of a sipper tube (conditioned stimulus, CS) with food (unconditioned stimulus, US) will induce Pavlovian autoshaping conditioned responses (CRs), consisting of drinking of either 6% ethanol or water from the sipper CS. This study also tests predictions derived from the autoshaping model by asking if sipper CS-directed drinking will be retained, despite the absence of training for several weeks, and, in addition, if drinking rate is a negative function of sipper CS duration. Autoshaping procedures, conducted in two daily sessions, consisted of the brief insertion of the sipper tube CS followed by the response-independent presentation of food US. For the Ethanol group (n = 8), the sipper CS contained 6% ethanol, whereas for the Water group (n = 8), the sipper CS contained tap water. Saccharin fading procedures were employed, whereas for both groups, during days 1-19, the sipper CS contained 0.1% saccharin, and thereafter across training days the concentration of saccharin was gradually reduced (0.07, 0.035, 0.0%). Following elimination of saccharin, both groups were maintained in their home cages during a 27-day retention interval, and then re-evaluated for autoshaping of drinking of unsweetened ethanol and water. Thereafter, across days, the duration of access to the sipper CS (5.0, 7.5, 10.0, 15.0 s) during each autoshaping trial was increased. Both groups increased drinking across the first 19 days of training with sipper CS-food US pairings, and, at 0.0% saccharin, the Ethanol group consumed 14.76 ml of 6% ethanol per day, resulting in a daily ethanol consumption of 2.77 g/kg. For both groups, daily levels of drinking before and after the 27-day retention interval were comparable, attesting to the durability of the acquired drinking effects. At each CS duration, the Ethanol group consumed more millilitres of fluid per day than did the Water group, and for the Ethanol group, peak drinking of 24.0 ml of 6% ethanol per

Acute Ethanol Gavage Attenuates Hemorrhage/Resuscitation-Induced Hepatic Oxidative Stress in Rats

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B. Relja

2012-01-01

Full Text Available Acute ethanol intoxication increases the production of reactive oxygen species (ROS. Hemorrhagic shock with subsequent resuscitation (H/R also induces ROS resulting in cellular and hepatic damage in vivo. We examined the role of acute ethanol intoxication upon oxidative stress and subsequent hepatic cell death after H/R. 14 h before H/R, rats were gavaged with single dose of ethanol or saline (5 g/kg, EtOH and ctrl; H/R_EtOH or H/R_ctrl, resp.. Then, rats were hemorrhaged to a mean arterial blood pressure of 30±2 mmHg for 60 min and resuscitated. Two control groups underwent surgical procedures without H/R (sham_ctrl and sham_EtOH, resp.. Liver tissues were harvested at 2, 24, and 72 h after resuscitation. EtOH-gavage induced histological picture of acute fatty liver. Hepatic oxidative (4-hydroxynonenal, 4-HNE and nitrosative (3-nitrotyrosine, 3-NT stress were significantly reduced in EtOH-gavaged rats compared to controls after H/R. Proapoptotic caspase-8 and Bax expressions were markedly diminished in EtOH-gavaged animals compared with controls 2 h after resuscitation. EtOH-gavage increased antiapoptotic Bcl-2 gene expression compared with controls 2 h after resuscitation. iNOS protein expression increased following H/R but was attenuated in EtOH-gavaged animals after H/R. Taken together, the data suggest that acute EtOH-gavage may attenuate H/R-induced oxidative stress thereby reducing cellular injury in rat liver.

Attenuation of ethanol abstinence-induced anxiety- and depressive-like behavior by the phosphodiesterase-4 inhibitor rolipram in rodents.

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Gong, Mei-Fang; Wen, Rui-Ting; Xu, Ying; Pan, Jian-Chun; Fei, Ning; Zhou, Yan-Meng; Xu, Jiang-Ping; Liang, Jian-Hui; Zhang, Han-Ting

2017-10-01

Withdrawal symptoms stand as a core feature of alcohol dependence. Our previous results have shown that inhibition of phosphodiesterase-4 (PDE4) decreased ethanol seeking and drinking in alcohol-preferring rodents. However, little is known about whether PDE4 is involved in ethanol abstinence-related behavior. The objective of this study was to characterize the role of PDE4 in the development of anxiety- and depressive-like behavior induced by abstinence from ethanol exposure in different animal models. Using three rodent models of ethanol abstinence, we examined the effects of rolipram, a prototypical, selective PDE4 inhibitor, on (1) anxiety-like behavior induced by repeated ethanol abstinence in the elevated plus maze test in fawn-hooded (FH/Wjd) rats, (2) anxiety-like behavior in the open-field test and light-dark transition test following acute ethanol abstinence in C57BL/6J mice, and (3) anxiety- and depressive-like behavior induced by protracted ethanol abstinence in the elevated plus maze, forced-swim, and tail-suspension tests in C57BL/6J mice. Pretreatment with rolipram (0.1 or 0.2 mg/kg) significantly increased entries and time spent in the open arms of the elevated plus maze test in rats with repeated ethanol abstinence. Similarly, in mice with acute ethanol abstinence, administration of rolipram (0.25 or 0.5 mg/kg) dose-dependently increased the crossings in the central zone of the open-field test and duration and transitions on the light side of the light-dark transition test, suggesting anxiolytic-like effects of rolipram. Consistent with these, chronic treatment with rolipram (0.1, 0.3, or 1.0 mg/kg) increased entries in the open arms of the elevated plus maze test; it also reduced the increased duration of immobility in both the forced-swim and tail-suspension tests in mice after protracted ethanol abstinence, suggesting antidepressant-like effects of rolipram. These results provide the first demonstration for that PDE4 plays a role in modulating

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

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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.

Solanum nigrum Protects against Hepatic Fibrosis via Suppression of Hyperglycemia in High-Fat/Ethanol Diet-Induced Rats

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Cheng-Jeng Tai

2016-02-01

Full Text Available Background: Advanced glycation end products (AGEs signal through the receptor for AGE (RAGE, which can lead to hepatic fibrosis in hyperglycemia and hyperlipidemia. We investigated the inhibitory effect of aqueous extracts from Solanum nigrum (AESN on AGEs-induced RAGE signaling and activation of hepatic stellate cells (HSCs and hyperglycemia induced by high-fat diet with ethanol. Methods: An animal model was used to evaluate the anti-hepatic fibrosis activity of AESN in rats fed a high-fat diet (HFD; 30% with ethanol (10%. Male Wistar rats (4 weeks of age were randomly divided into four groups (n = 6: (1 control (basal diet; (2 HFD (30% + ethanol (10% (HFD/ethanol; (3 HFD/ethanol + AESN (100 mg/kg, oral administration; and (4 HFD/ethanol + pioglitazone (10 mg/kg, oral administration and treated with HFD for 6 months in the presence or absence of 10% ethanol in dietary water. Results: We found that AESN improved insulin resistance and hyperinsulinemia, and downregulated lipogenesis via regulation of the peroxisome proliferator-activated receptor α (PPARα, PPARγ co-activator (PGC-1α, carbohydrate response element-binding protein (ChREBP, acetyl-CoA carboxylase (ACC, and fatty acid synthase (FAS mRNA levels in the liver of HFD/ethanol-treated rats. In turn, AESN may delay and inhibit the progression of hepatic fibrosis, including α-smooth muscle actin (α-SMA inhibition and MMP-2 production. Conclusions: These results suggest that AESN may be further explored as a novel anti-fibrotic strategy for the prevention of liver disease.

Effect of isopregnanolone on rapid tolerance to the anxiolytic effect of ethanol

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Debatin Thaize

2006-01-01

Full Text Available OBJETIVE: It has been shown that neurosteroids can either block or stimulate the development of chronic and rapid tolerance to the incoordination and hypothermia caused by ethanol consumption. The aim of the present study was to investigate the influence of isopregnanolone on the development of rapid tolerance to the anxiolytic effect of ethanol in mice. METHOD: Male Swiss mice were pretreated with isopregnanolone (0.05, 0.10 or 0.20 mg/kg 30 min before administration of ethanol (1.5 g/kg. Twenty-four hours later, all animals we tested using the plus-maze apparatus. The first experiment defined the doses of ethanol that did or did not induce rapid tolerance to the anxiolytic effect of ethanol. In the second, the influence of pretreatment of mice with isopregnanolone (0.05, 0.10 or 0.20 mg/kg on rapid tolerance to ethanol (1.5 g/kg was studied. CONCLUSIONS: The results show that pretreatment with isopregnanolone interfered with the development of rapid tolerance to the anxiolytic effect of ethanol.

Hyperalgesic effect induced by barbiturates, midazolam and ethanol: pharmacological evidence for GABA-A receptor involvement

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M.A.K.F. Tatsuo

1997-02-01

Full Text Available The involvement of GABA-A receptors in the control of nociception was studied using the tail-flick test in rats. Non-hypnotic doses of the barbiturates phenobarbital (5-50 mg/kg, pentobarbital (17-33 mg/kg, and thiopental (7.5-30 mg/kg, of the benzodiazepine midazolam (10 mg/kg or of ethanol (0.4-1.6 g/kg administered by the systemic route reduced the latency for the tail-flick response, thus inducing a 'hyperalgesic' state in the animals. In contrast, non-convulsant doses of the GABA-A antagonist picrotoxin (0.12-1.0 mg/kg administered systemically induced an increase in the latency for the tail-flick response, therefore characterizing an 'antinociceptive' state. Previous picrotoxin (0.12 mg/kg treatment abolished the hyperalgesic state induced by effective doses of the barbiturates, midazolam or ethanol. Since phenobarbital, midazolam and ethanol reproduced the described hyperalgesic effect of GABA-A-specific agonists (muscimol, THIP, which is specifically antagonized by the GABA-A antagonist picrotoxin, our results suggest that GABA-A receptors are tonically involved in the modulation of nociception in the rat central nervous system

Ethanol induces cell-cycle activity and reduces stem cell diversity to alter both regenerative capacity and differentiation potential of cerebral cortical neuroepithelial precursors

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Tingling Joseph D

2005-09-01

Full Text Available Abstract Background The fetal cortical neuroepithelium is a mosaic of distinct progenitor populations that elaborate diverse cellular fates. Ethanol induces apoptosis and interferes with the survival of differentiating neurons. However, we know little about ethanol's effects on neuronal progenitors. We therefore exposed neurosphere cultures from fetal rat cerebral cortex, to varying ethanol concentrations, to examine the impact of ethanol on stem cell fate. Results Ethanol promoted cell cycle progression, increased neurosphere number and increased diversity in neurosphere size, without inducing apoptosis. Unlike controls, dissociated cortical progenitors exposed to ethanol exhibited morphological evidence for asymmetric cell division, and cells derived from ethanol pre-treated neurospheres exhibited decreased proliferation capacity. Ethanol significantly reduced the numbers of cells expressing the stem cell markers CD117, CD133, Sca-1 and ABCG2, without decreasing nestin expression. Furthermore, ethanol-induced neurosphere proliferation was not accompanied by a commensurate increase in telomerase activity. Finally, cells derived from ethanol-pretreated neurospheres exhibited decreased differentiation in response to retinoic acid. Conclusion The reduction in stem cell number along with a transient ethanol-driven increase in cell proliferation, suggests that ethanol promotes stem to blast cell maturation, ultimately depleting the reserve proliferation capacity of neuroepithelial cells. However, the lack of a concomitant change in telomerase activity suggests that neuroepithelial maturation is accompanied by an increased potential for genomic instability. Finally, the cellular phenotype that emerges from ethanol pre-treated, stem cell depleted neurospheres is refractory to additional differentiation stimuli, suggesting that ethanol exposure ablates or delays subsequent neuronal differentiation.

Protective Effect of Aqueous and Ethanolic Extracts of Portulaca Oleracea Against Cisplatin Induced Nephrotoxicity

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Gholamreza Karimi

2010-04-01

Full Text Available Objective(sPortulaca oleracea L. is a herbaceous weed from portulacaceae family. It can be found in many parts of the world. Modern pharmacological studies have demonstrated that P. oleracea have antioxidant effects. The protective effect of aqueous and ethanolic extract of P. oleracea against cisplatin-induced renal toxicity was studied in rats.Materials and MethodsSingle intraperitoneal injection of 4 mg/kg cisplatin was administrated to rats. After 5 days, blood urea nitrogen (BUN and serum creatinine (Scr concentration were determined. Effect of aqueous and ethanolic extracts, before and after cisplatin injection on BUN and Scr, as well as morphological renal damage, was evaluated. ResultsIt was indicated that treatment with aqueous and ethanolic extracts of P. oleracea in the highest dose (0.8 and 2 g/ kg, 6 and 12 hr before cisplatin injection reduced BUN and Scr. Tubular necrotic damage was not observed either. ConclusionResults suggest that P. oleracea extract may protect against cisplatin-induced renal toxicity and might serve as a novel combination agent with cisplan to limit renal injury.

Protective effect of bovine milk against HCl and ethanol-induced gastric ulcer in mice.

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Yoo, Jeong-Hyun; Lee, Jeong-Sang; Lee, You-Suk; Ku, SaeKwang; Lee, Hae-Jeung

2018-05-01

The purpose of this study was to investigate the gastroprotective effects of bovine milk on an acidified ethanol (HCl-ethanol) mixture that induced gastric ulcers in a mouse model. Mice received different doses of commercial fresh bovine milk (5, 10, and 20 mL/kg of body weight) by oral gavage once a day for 14 d. One hour after the last oral administration of bovine milk, the HCl-ethanol mixture was orally intubated to provoke severe gastric damage. Our results showed that pretreatment with bovine milk significantly suppressed the formation of gastric mucosa lesions. Pretreatment lowered gastric myeloperoxidase and increased gastric mucus contents and antioxidant enzymes catalase and superoxide dismutase. Administration of bovine milk increased nitrate/nitrite levels and decreased the malondialdehyde levels and the expression of proinflammatory genes, including transcription factor nuclear factor-κB, cyclooxygenase-2, and inducible nitric oxide synthase in the stomach of mice. These results suggest that bovine milk can prevent the development of gastric ulcer caused by acid and alcohol in mice. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Ameliorative Activity of Ethanolic Extract of Artocarpus heterophyllus Stem Bark on Alloxan-induced Diabetic Rats.

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Ajiboye, Basiru Olaitan; Adeleke Ojo, Oluwafemi; Adeyonu, Oluwatosin; Imiere, Oluwatosin; Emmanuel Oyinloye, Babatunji; Ogunmodede, Oluwafemi

2018-03-01

Purpose: Diabetes mellitus is one of the major endocrine disorders, characterized by impaired insulin action and deficiency. Traditionally, Artocarpus heterophyllus stem bark has been reputably used in the management of diabetes mellitus and its complications. The present study evaluates the ameliorative activity of ethanol extract of Artocarpus heterophyllus stem bark in alloxan-induced diabetic rats. Methods: Diabetes mellitus was induced by single intraperitoneal injection of 150 mg/kg body weight of alloxan and the animals were orally administered with 50, 100 and 150 mg/kg body weight ethanol extract of Artocarpus heterophyllus stem bark once daily for 21 days. Results: At the end of the intervention, diabetic control rats showed significant (pArtocarpus heterophyllus stem bark most especially at 150 mg/kg body weight which exhibited no significant (p>0.05) different with non-diabetic rats. Conclusion: The results suggest that ethanol extract of Artocarpus heterophyllus stem bark may be useful in ameliorating complications associated with diabetes mellitus patients.

Ganoderma Lucidum Pharmacopuncture for Teating Ethanol-induced Chronic Gastric Ulcers in Rats

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Jae-Heung Park

2015-03-01

Full Text Available Objectives: The stomach is a sensitive digestive organ that is susceptible to exogenous pathogens from the diet. In response to such pathogens, the stomach induces oxidative stress, which might be related to the development of both gastric organic disorders such as gastritis, gastric ulcers, and gastric cancer, and functional disorders such as functional dyspepsia. This study was accomplished to investigate the effect of Ganoderma lucidum pharmacopuncture (GLP on chronic gastric ulcers in rats. Methods: The rats were divided into 4 groups of 8 animals each: the normal, the control, the normal saline (NP and the GLP groups. In this study, the modified ethanol gastritis model was used. The rats were administrated 56% ethanol orally every other day. The dose of ethanol was 8 g/kg body weight. The normal group received the same amount of normal saline instead of ethanol. The NP and the GLP groups were treated with injection of saline and GLP respectively. The control group received no treatment. Two local acupoints CV12 (中脘 and ST36 (足三里 were used. All laboratory rats underwent treatment for 15 days. On last day, the rats were sacrificed and their stomachs were immediately excised. Results: Ulcers of the gastric mucosa appeared as elongated bands of hemorrhagic lesions parallel to the long axis of the stomach. In the NP and GLP groups, the injuries to the gastric mucosal injuries were not as severe as they were in the control group. Wound healings of the chronic gastric ulcers was promoted by using GLP and significant alterations of the indices in the gastric mucosa were observed. Such protection was demonstrated by gross appearance, histology and immunehistochemistry staining for Bcl-2-associated X (BAX, B-cell lymphoma 2 (Bcl-2 and Transforming growth factor-beta 1 (TGF-β1. Conclusion: These results suggest that GLP at CV12 and ST36 can provide significant protection to the gastric mucosa against an ethanol induced chronic gastric ulcer.

Microglial-derived miRNA let-7 and HMGB1 contribute to ethanol-induced neurotoxicity via TLR7.

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Coleman, Leon G; Zou, Jian; Crews, Fulton T

2017-01-25

Toll-like receptor (TLR) signaling is emerging as an important component of neurodegeneration. TLR7 senses viral RNA and certain endogenous miRNAs to initiate innate immune responses leading to neurodegeneration. Alcoholism is associated with hippocampal degeneration, with preclinical studies linking ethanol-induced neurodegeneration with central innate immune induction and TLR activation. The endogenous miRNA let-7b binds TLR7 to cause neurodegeneration. TLR7 and other immune markers were assessed in postmortem human hippocampal tissue that was obtained from the New South Wales Tissue Bank. Rat hippocampal-entorhinal cortex (HEC) slice culture was used to assess specific effects of ethanol on TLR7, let-7b, and microvesicles. We report here that hippocampal tissue from postmortem human alcoholic brains shows increased expression of TLR7 and increased microglial activation. Using HEC slice culture, we found that ethanol induces TLR7 and let-7b expression. Ethanol caused TLR7-associated neuroimmune gene induction and initiated the release let-7b in microvesicles (MVs), enhancing TLR7-mediated neurotoxicity. Further, ethanol increased let-7b binding to the danger signaling molecule high mobility group box-1 (HMGB1) in MVs, while reducing let-7 binding to classical chaperone protein argonaute (Ago2). Flow cytometric analysis of MVs from HEC media and analysis of MVs from brain cell culture lines found that microglia were the primary source of let-7b and HMGB1-containing MVs. Our results identify that ethanol induces neuroimmune pathology involving the release of let-7b/HMGB1 complexes in microglia-derived microvesicles. This contributes to hippocampal neurodegeneration and may play a role in the pathology of alcoholism.

Value Chain Structures that Define European Cellulosic Ethanol Production

DEFF Research Database (Denmark)

Gregg, Jay Sterling; Bolwig, Simon; Hansen, Teis

2017-01-01

production plants across Europe from a global value chain (GVC) perspective. We find that most CE production plants in the EU focus largely on intellectual property and are therefore only at the pilot or demonstration scale. Crescentino, the largest CE production facility in Europe, is also more interested...... petroleum markets and higher financial risks. We argue that, to increase CE production, policies should consider value chains, promote the wider bio-economy of products and focus on economies of scope. Whereas the EU and its member states have ethanol quotas and blending targets, a more effective policy......Production of cellulosic ethanol (CE) has not yet reached the scale envisaged by the literature and industry. This study explores CE production in Europe to improve understanding of the motivations and barriers associated with this situation. To do this, we conduct a case study-based analysis of CE...

Concomitant stress potentiates the preference for, and consumption of, ethanol induced by chronic pre-exposure to ethanol.

Science.gov (United States)

Morais-Silva, G; Fernandes-Santos, J; Moreira-Silva, D; Marin, M T

2016-01-01

Ethanol abuse is linked to several acute and chronic injuries that can lead to health problems. Ethanol addiction is one of the most severe diseases linked to the abuse of this drug. Symptoms of ethanol addiction include compulsive substance intake and withdrawal syndrome. Stress exposure has an important role in addictive behavior for many drugs of abuse (including ethanol), but the consequences of stress and ethanol in the organism when these factors are concomitant results in a complex interaction. We investigated the effects of concomitant, chronic administration of ethanol and stress exposure on the withdrawal and consumption of, as well as the preference for, ethanol in mice. Male Swiss mice (30-35 g, 8-10 per group) were exposed to an ethanol liquid diet as the only source of food for 15 days. In the final 5 days, they were exposed to forced swimming stress. Twelve hours after removal of the ethanol liquid diet, animals were evaluated for ethanol withdrawal by measuring anxiety-related behaviors and locomotor activity. Twenty-four hours after evaluation of ethanol withdrawal, they were evaluated for voluntary consumption of ethanol in a "three-bottle choice" paradigm. Mice exposed to chronic consumption of ethanol had decreased locomotor activity during withdrawal. Contrary to our expectations, a concomitant forced swimming stress did not aggravate ethanol withdrawal. Nevertheless, simultaneous ethanol administration and stress exposure increased voluntary consumption of ethanol, mainly solutions containing high concentrations of ethanol. These results showed that stressful situations during ethanol intake may aggravate specific addiction-related behaviors.

Concomitant stress potentiates the preference for, and consumption of, ethanol induced by chronic pre-exposure to ethanol

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G. Morais-Silva

2016-01-01

Full Text Available Ethanol abuse is linked to several acute and chronic injuries that can lead to health problems. Ethanol addiction is one of the most severe diseases linked to the abuse of this drug. Symptoms of ethanol addiction include compulsive substance intake and withdrawal syndrome. Stress exposure has an important role in addictive behavior for many drugs of abuse (including ethanol, but the consequences of stress and ethanol in the organism when these factors are concomitant results in a complex interaction. We investigated the effects of concomitant, chronic administration of ethanol and stress exposure on the withdrawal and consumption of, as well as the preference for, ethanol in mice. Male Swiss mice (30–35 g, 8-10 per group were exposed to an ethanol liquid diet as the only source of food for 15 days. In the final 5 days, they were exposed to forced swimming stress. Twelve hours after removal of the ethanol liquid diet, animals were evaluated for ethanol withdrawal by measuring anxiety-related behaviors and locomotor activity. Twenty-four hours after evaluation of ethanol withdrawal, they were evaluated for voluntary consumption of ethanol in a “three-bottle choice” paradigm. Mice exposed to chronic consumption of ethanol had decreased locomotor activity during withdrawal. Contrary to our expectations, a concomitant forced swimming stress did not aggravate ethanol withdrawal. Nevertheless, simultaneous ethanol administration and stress exposure increased voluntary consumption of ethanol, mainly solutions containing high concentrations of ethanol. These results showed that stressful situations during ethanol intake may aggravate specific addiction-related behaviors.

Hepatoprotective effects of Arctium lappa Linne on liver injuries induced by chronic ethanol consumption and potentiated by carbon tetrachloride.

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Lin, Song-Chow; Lin, Chia-Hsien; Lin, Chun-Ching; Lin, Yun-Ho; Chen, Chin-Fa; Chen, I-Cheng; Wang, Li-Ya

2002-01-01

Arctium lappa Linne (burdock) is a perennial herb which is popularly cultivated as a vegetable. In order to evaluate its hepatoprotective effects, a group of rats (n = 10) was fed a liquid ethanol diet (4 g of absolute ethanol/ 80 ml of liquid basal diet) for 28 days and another group (n = 10) received a single intraperitoneal injection of 0.5 ml/kg carbon tetrachloride (CCl(4)) in order to potentiate the liver damage on the 21st day (1 day before the beginning of A. lappa treatment). Control group rats were given a liquid basal diet which did not contain absolute ethanol. When 300 mg/kg A. lappa was administered orally 3 times per day in both the 1-day and 7-day treatment groups, some biochemical and histopathological parameters were significantly altered, both in the ethanol group and the groups receiving ethanol supplemented with CCl(4). A. lappa significantly improved various pathological and biochemical parameters which were worsened by ethanol plus CCl(4)-induced liver damage, such as the ethanol plus CCl(4)-induced decreases in total cytochrome P-450 content and NADPH-cytochrome c reductase activity, increases in serum triglyceride levels and lipid peroxidation (the deleterious peroxidative and toxic malondialdehyde metabolite may be produced in quantity) and elevation of serum transaminase levels. It could even restore the glutathione content and affect the histopathological lesions. These results tended to imply that the hepatotoxicity induced by ethanol and potentiated by CCl(4) could be alleviated with 1 and 7 days of A. lappa treatment. The hepatoprotective mechanism of A. lappa could be attributed, at least in part, to its antioxidative activity, which decreases the oxidative stress of hepatocytes, or to other unknown protective mechanism(s). Copyright 2002 National Science Council, ROC and S. Karger AG, Basel

Ethanol-induced conditioned taste aversion in male sprague-dawley rats: impact of age and stress.

Science.gov (United States)

Anderson, Rachel I; Varlinskaya, Elena I; Spear, Linda P

2010-12-01

Age-specific characteristics may contribute to the elevation in ethanol intake commonly reported among adolescents compared to adults. This study was designed to examine age-related differences in sensitivity to ethanol's aversive properties using a conditioned taste aversion (CTA) procedure with sucrose serving as the conditioned stimulus (CS). Given that ontogenetic differences in responsiveness to stressors have been previously reported, the role of stressor exposure on the development of CTA was also assessed. Experiment 1 examined the influence of 5 days of prior restraint stress exposure on the expression of CTA in a 2-bottle test following 1 pairing of a sucrose solution with ethanol. In Experiment 2, the effects of 7 days of social isolation on the development of CTA were observed using a 1-bottle test following multiple sucrose-ethanol pairings. This study revealed age-related differences in the development of ethanol-induced CTA. In Experiment 1, adolescents required a higher dose of ethanol than adults to demonstrate an aversion. In Experiment 2, adolescents required not only a higher ethanol dose but also more pairings of ethanol with the sucrose CS. No effects of prior stressor exposure were observed in either experiment. Together, these experiments demonstrate an adolescent-specific insensitivity to the aversive properties of ethanol that elicit CTA, a pattern not influenced by repeated restraint stress or housing in social isolation. This age-related insensitivity to the dysphoric effects of ethanol is consistent with other work from our laboratory, adding further to the evidence that adolescent rats are less susceptible to negative consequences of ethanol that may serve as cues to curb consumption. Copyright © 2010 by the Research Society on Alcoholism.

Immobilization of Saccharomyces Cerevisiae in Rice Hulls for Ethanol Production

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Edita Martini

2011-05-01

Full Text Available The whole cell immobilization in ethanol fermentation can be done by using natural carriers or through synthetic carriers. All of these methods have the same purpose of retaining high cell concentrations within a certain defined region of space which leads to higher ethanol productivity. Lignocellulosic plant substance represents one of highly potential sources in ethanol production. Some studies have found that cellulosic substances substances can also be used as a natural carrier in cell immobilization by re-circulating pre-culture medium into a reactor. In this experiment, rice hulls without any treatment were used to immobilize Saccharomyces cerevisiae through semi solid state incubation combined with re-circulating pre-culture medium. The scanning electron microscopy (SEM pictures of the carrier show that the yeast cells are absorbed and embedded to the rice hull pore. In liquid batch fermentation system with an initial sugar concentration of 50 g/L, nearly 100% total sugar was consumed after 48 hours. This resulted in an ethanol yield of 0.32 g ethanol/g glucose, which is 62.7% of the theoretical value. Ethanol productivity of 0.59 g/(L.h is 2.3 fold higher than that of free cells which is 0.26 g/(L.h. An effort to reuse the immobilized cells in liquid fermentation system showed poor results due to cell desorption in the first batch which led to high sugar concentration inhibitory effect in the second batch fermentation. This might be solved by using semi solid fermentation process in the future work.

Ascorbic acid supplementation enhances recovery from ethanol induced inhibition of Leydig cell steroidogenesis than abstention in male guinea pigs.

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

2014-01-15

The impact of ascorbic acid supplementation against ethanol induced Leydig cell toxicity was studied in guinea pigs. Male guinea pigs were exposed to ethanol (4g/kgb.wt.) for 90 days. After 90 days, ethanol administration was completely stopped and animals in the ethanol group were divided into abstention group and ascorbic acid supplemented group (25mg/100gb.wt.) and those in control group were maintained as control and control+ascorbic acid group. Ethanol administration reduced the serum testosterone and LH (luteinising hormone) levels and elevated estradiol levels. Cholesterol levels in Leydig cell were increased whereas the mRNA and protein expressions of StAR (steroidogenic acute regulatory) protein, cytochrome P450scc (cytochrome p450side chain cleavage enzyme), 3β-HSD (3β-hydroxysteroid dehydrogenase), 17β-HSD (17β-hydroxysteroid dehydrogenase) and LH receptor were drastically reduced. Administration of ascorbic acid resulted in alteration of all these parameters indicating enhanced recovery from ethanol induced inhibition of Leydig cell steroidogenesis. Although abstention could also reduce the inhibition of steroidogenesis, this was lesser in comparison with ascorbic acid supplemented group. © 2013 Published by Elsevier B.V.

Ethanol cellular defense induce unfolded protein response in yeast

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Elisabet eNavarro-Tapia

2016-02-01

Full Text Available Ethanol is a valuable industrial product and a common metabolite used by many cell types. However, this molecule produces high levels of cytotoxicity affecting cellular performance at several levels. In the presence of ethanol, cells must adjust some of their components, such as the membrane lipids to maintain homeostasis. In the case of microorganism as Saccharomyces cerevisiae, ethanol is one of the principal products of their metabolism and is the main stress factor during fermentation. Although many efforts have been made, mechanisms of ethanol tolerance are not fully understood and very little evidence is available to date for specific signaling by ethanol in the cell. This work studied two Saccharomyces cerevisiae strains, CECT10094 and Temohaya-MI26, isolated from flor wine and agave fermentation (a traditional fermentation from Mexico respectively, which differ in ethanol tolerance, in order to understand the molecular mechanisms underlying the ethanol stress response and the reasons for different ethanol tolerance. The transcriptome was analyzed after ethanol stress and, among others, an increased activation of genes related with the unfolded protein response (UPR and its transcription factor, Hac1p, was observed in the tolerant strain CECT10094. We observed that this strain also resist more UPR agents than Temohaya-MI26 and the UPR-ethanol stress correlation was corroborated observing growth of 15 more strains and discarding UPR correlation with other stresses as thermal or oxidative stress. Furthermore, higher activation of UPR pathway in the tolerant strain CECT10094 was observed using a UPR mCherry reporter. Finally, we observed UPR activation in response to ethanol stress in other S. cerevisiae ethanol tolerant strains as the wine strains T73 and EC1118. This work demonstrates that the UPR pathway is activated under ethanol stress occurring in a standard fermentation and links this response to an enhanced ethanol tolerance. Thus

Autoshaping induces ethanol drinking in nondeprived rats: evidence of long-term retention but no induction of ethanol preference.

Science.gov (United States)

Tomie, Arthur; Kuo, Teresa; Apor, Khristine R; Salomon, Kimberly E; Pohorecky, Larissa A

2004-04-01

The effects of autoshaping procedures (paired vs. random) and sipper fluid (ethanol vs. water) on sipper-directed drinking were evaluated in male Long-Evans rats maintained with free access to food and water. For the paired/ethanol group (n=16), autoshaping procedures consisted of presenting the ethanol sipper (containing 0% to 28% unsweetened ethanol) conditioned stimulus (CS) followed by the response-independent presentation of food unconditioned stimulus (US). The random/ethanol group (n=8) received the sipper CS and food US randomly with respect to one another. The paired/water group (n=8) received only water in the sipper CS. The paired/ethanol group showed higher grams per kilogram ethanol intake than the random/ethanol group did at ethanol concentrations of 8% to 28%. The paired/ethanol group showed higher sipper CS-directed milliliter fluid consumption than the paired/water group did at ethanol concentrations of 1% to 6%, and 15%, 16%, 18%, and 20%. Following a 42-day retention interval, the paired/ethanol group showed superior retention of CS-directed drinking of 18% ethanol, relative to the random/ethanol group, and superior retention of CS-directed milliliter fluid drinking relative to the paired/water group. When tested for home cage ethanol preference using limited access two-bottle (28% ethanol vs. water) procedures, the paired/ethanol and random/ethanol groups did not differ on any drinking measures.

Laser induced augmentation of silver nanospheres to nanowires in ethanol fostered by Poly Vinyl Pyrrolidone

Energy Technology Data Exchange (ETDEWEB)

Sebastian, Suneetha, E-mail: sunikutty@gmail.com; Linslal, C.L.; Vallabhan, C.P.G.; Nampoori, V.P.N.; Radhakrishnan, P.; Kailasnath, M.

2014-11-30

Highlights: • Silver nanospheres are synthesised in ethanol containing Poly Vinyl Pyrrolidone which acts as a polymeric capping agent to nanoparticles thus improving its stability. • Laser irradiation onto the colloidal solution of silver nanoparticles produced well defined nanowires through ripening mechanism promoted by Poly Vinyl Pyrrolidone. • Nanowires so formed are having an average length of 8.7 μm and width of 160 nm. - Abstract: Stable uniform silver nanospheres having an average diameter of 45 nm are synthesised in ethanol containing Poly Vinyl Pyrrolidone using Laser Ablation in Liquid technique. Further irradiation of the nanocolloidal solution by focussed laser beam produced stable well defined silver nanowires through ripening mechanism fostered by the presence of Poly Vinyl Pyrrolidone. Confirmation of the mechanism is obtained from Transmission Electron Microscopic images of the nanocolloidal solution irradiated for different time durations.

Physicochemical properties, antioxidant activities and protective effect against acute ethanol-induced hepatic injury in mice of foxtail millet (Setaria italica) bran oil.

Science.gov (United States)

Pang, Min; He, Shujian; Wang, Lu; Cao, Xinmin; Cao, Lili; Jiang, Shaotong

2014-08-01

This study was designed to investigate physicochemical characterization of the oil extracted from foxtail millet bran (FMBO), and the antioxidant and hepatoprotective effects against acute ethanol-induced hepatic injury in mice. GC-MS analysis revealed that unsaturated fatty acids (UFAs) account for 83.76% of the total fatty acids; in particular, the linoleic acid (C18:2) is the predominant polyunsaturated fatty acid (PUFA), and the compounds of squalene and six phytosterols (or phytostanols) were identified in unsaponifiable matter of FMBO. The antioxidant activity examination of FMBO in vitro showed highly ferric-reducing antioxidant power and scavenging effects against DPPH· and HO· radicals. Furthermore, the protective effect of FMBO against acute hepatic injuries induced by ethanol was verified in mice. In this, intragastric administration with different dosages of FMBO in mice ahead of acute ethanol administration could observably antagonize the ethanol-induced increases in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), and the hepatic malondialdehyde (MDA) levels, respectively, along with enhanced hepatic superoxide dismutase (SOD) levels relative to the control. Hepatic histological changes were also observed and confirmed that FMBO is capable of attenuating ethanol-induced hepatic injury.

Effects of ethanol on social avoidance induced by chronic social defeat stress in mice.

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Favoretto, Cristiane A; Macedo, Giovana C; Quadros, Isabel M H

2017-01-01

In rodents, chronic social defeat stress promotes deficits in social interest and social interaction. We further explored these antisocial effects by comparing the consequences of two different defeat stress protocols (episodic vs. continuous stress) in a social investigation test. We expected that continuous, but not episodic, stress would induce social deficits in this model. Furthermore, we tested whether a potentially anxiolytic dose of ethanol reverses social deficits induced by defeat stress. Male Swiss mice were exposed to a 10-day social defeat protocol, using daily confrontations with an aggressive resident mouse. Episodic stress consisted of brief defeat episodes, after which the defeated mouse was returned to its home cage, until the next defeat 24 h later (n = 7-11/group). For continuous stress, similar defeat episodes were followed by cohabitation with the aggressive resident for 24 h, separated by a perforated divider, until the following defeat (n = 8-14/group). Eight days after stress termination, defeated and control mice were assessed in a social investigation test, after treatment with ethanol (1.0 g/kg, i.p.) or 0.9% saline. Considering the time spent investigating a social target, mice exposed to episodic or continuous social stress showed less social investigation than controls (p stress or ethanol. Thus, a history of social defeat stress, whether episodic or continuous, promotes deficits in social investigation that were not reversed by acute treatment with ethanol.

Inhibition of vascular endothelial growth factor signaling facilitates liver repair from acute ethanol-induced injury in zebrafish

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Changwen Zhang

2016-11-01

Full Text Available Alcoholic liver disease (ALD results from alcohol overconsumption and is among the leading causes of liver-related morbidity and mortality worldwide. Elevated expression of vascular endothelial growth factor (VEGF and its receptors has been observed in ALD, but how it contributes to ALD pathophysiology is unclear. Here, we investigated the impact of VEGF signaling inhibition on an established zebrafish model of acute alcoholic liver injury. Kdrl activity was blocked by chemical inhibitor treatment or by genetic mutation. Exposing 4-day-old zebrafish larvae to 2% ethanol for 24 h induced hepatic steatosis, angiogenesis and fibrogenesis. The liver started self-repair once ethanol was removed. Although inhibiting Kdrl did not block the initial activation of hepatic stellate cells during ethanol treatment, it suppressed their proliferation, extracellular matrix protein deposition and fibrogenic gene expression after ethanol exposure, thus enhancing the liver repair. It also ameliorated hepatic steatosis and attenuated hepatic angiogenesis that accelerated after the ethanol treatment. qPCR showed that hepatic stellate cells are the first liver cell type to increase the expression of VEGF ligand and receptor genes in response to ethanol exposure. Both hepatic stellate cells and endothelial cells, but not hepatic parenchymal cells, expressed kdrl upon ethanol exposure and were likely the direct targets of Kdrl inhibition. Ethanol-induced steatosis and fibrogenesis still occurred in cloche mutants that have hepatic stellate cells but lack hepatic endothelial cells, and Kdrl inhibition suppressed both phenotypes in the mutants. These results suggest that VEGF signaling mediates interactions between activated hepatic stellate cells and hepatocytes that lead to steatosis. Our study demonstrates the involvement of VEGF signaling in regulating sustained liver injuries after acute alcohol exposure. It also provides a proof of principle of using the

Lignans from Opuntia ficus-indica seeds protect rat primary hepatocytes and HepG2 cells against ethanol-induced oxidative stress.

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Kim, Jung Wha; Yang, Heejung; Kim, Hyeon Woo; Kim, Hong Pyo; Sung, Sang Hyun

2017-01-01

Bioactivity-guided isolation of Opuntia ficus-indica (Cactaceae) seeds against ethanol-treated primary rat hepatocytes yielded six lignan compounds. Among the isolates, furofuran lignans 4-6, significantly protected rat hepatocytes against ethanol-induced oxidative stress by reducing intracellular reactive oxygen species levels, preserving antioxidative defense enzyme activities, and maintaining the glutathione content. Moreover, 4 dose-dependently induced the heme oxygenase-1 expression in HepG2 cells.

Antidiabetic Activity Test of Ethanolic Seri Leave’s (Muntingia Calabura L.) Extract in Male Rats Induced by Alloxan

OpenAIRE

Herlina Herlina; Annisa Amriani; Indah Solihah; Rizky Sintya

2018-01-01

Antidiabetic activity test of ethanol extract of seri leave (Muntingia calabura L.) rats induced by alloxan has been done. Male wistar albino rats are used as animal models which divided into 6 groups, normal group (aquadest), negative control group (Na CMC 0,5%), positive control group (glibenclamide 0,43 mg/200 gBB), and 1, 2, and 3 treatment groups (ethanol extract of seri leave 65, 130, dan 260 mg/kgBB). Rats blood glucose level after induced intraperitoneally by alloxan 130 mg/kgBB can b...

Immobilization of yeast cells on hydrogel carriers obtained by radiation-induced polymerization

International Nuclear Information System (INIS)

Luzhao Xin; Carenza, M.; Kaetsu, Isao; Kumakura, Minoru; Yoshida, Masaru; Fujimura, Takashi

1992-01-01

Polymer hydrogels were obtained by radiation-induced copolymerization at -78 o C of aqueous solutions of acrylic and methacrylic esters. The matrices were characterized by equilibrium water content measurements, by optical microscopy observations and by scanning electron microscopy analysis. Yeast cells were immobilized on these hydrogels and the ethanol productivity by batch fermentation was determined. Matrix hydrophilicity and porosity were found to deeply influence the adhesion of yeast cells and, hence, the ethanol productivity. The latter as well as other physico-chemical properties were also affected by the presence of a crosslinking agent added in small amounts to the polymerizating mixture. (author)

Gastroprotective effect of diligustilide isolated from roots of Ligusticum porteri coulter & rose (Apiaceae) on ethanol-induced lesions in rats.

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Velázquez-Moyado, Josué A; Martínez-González, Alejandro; Linares, Edelmira; Bye, Robert; Mata, Rachel; Navarrete, Andrés

2015-11-04

The rhizome of Ligusticum porteri Coulter& Rose (LP) has been traditionally used by the ethnic group Raramuri in the North of México for treatment of diabetes, tuberculosis, stomachaches, diarrhea and ritual healing ceremonies. It is use as antiulcer remedy has been extended to all Mexico. To evaluate the gastroprotective activity of LP organic extracts and the major natural product diligustilide (DLG),using as experimental model the inhibition of the ethanol-induced lesions in rats. Gastric ulcers were induced by intragastric instillation of absolute ethanol (1 mL). We tested the gastroprotective activity of the organic extracts of LP and the pure compound DLG. The ulcer index (UI) was determined to measure the activity. In order to elucidate the action mechanism of DLG the animals were treated with L-NAME, N-ethylmalemide, Forskolin, 2',5'-dideoxyadenosine, Indomethacin, Glibenclameide, Diazoxide, NaHS and DL-Propargylglycine. The pylorus-ligated rat model was used to measure gastric secretion. The oral administration of organic extracts of Ligusticum porteri showed gastroprotective effect at 30 mg/Kg on ethanol induced gastric lesions; hexane and dichloromethane extracts were the most active. DLG was the major compound in the hexane extract. This compound at 10 mg/kg prevented significantly the gastric injuries induced by ethanol. The alkylation of endogenous non-protein-SH groups with N-ethylmaleimide abolished the gastroprotective effect of DLG and blocking the formation of endogenous prostaglandins by the pretreatment with indomethacin attenuated the gastroprotective effect of DLG. The gastroprotective activity demonstrated in this study tends to support the ethnomedical use of Ligusticum porteri roots. DLG, isolated as major compound of this medicinal plant has a clear gastroprotective effect on the ethanol-induced gastric lesions. The results suggest that the antiulcer activity of DLG depends on the participation of the endogenous non-protein -SH groups

Structural analysis of γ radiation-induced chromosomal aberrations observed by atomic force microscopy

International Nuclear Information System (INIS)

Qu Shuang; Chen Ying; Ge Shili; Liu Xiulin; Zhou Pingkun; Zhang Sa; Zhang Detian

2003-01-01

Objective: To find a new method for the measurement of radiation-induced damage, the structures of normal chromosomes and 60 Co γ-ray-induced chromosomal aberration were analyzed by atomic force microscopy. Methods: Normal and irradiated chromosomes of human peripheral blood lymphocytes were prepared, then three-dimensional structure and height of chromosomes were analyzed by atomic force microscopy. Results: Three-dimensional structures of normal chromosomes and dicentric aberration in irradiated chromosomes were observed clearly. The data of chromosome height were helpful to recognizing the dicentric aberrations. Conclusion: Atomic force microscopy providing three-dimension image and linear measurement is a new and valuable tool for structural analysis of radiation-induced chromosomal aberrations

Confocal laser scanning microscopy to estimate nanoparticles' human skin penetration in vitro.

Science.gov (United States)

Zou, Ying; Celli, Anna; Zhu, Hanjiang; Elmahdy, Akram; Cao, Yachao; Hui, Xiaoying; Maibach, Howard

2017-01-01

With rapid development of nanotechnology, there is increasing interest in nanoparticle (NP) application and its safety and efficacy on human skin. In this study, we utilized confocal laser scanning microscopy to estimate NP skin penetration. Three different-sized polystyrene NPs marked with red fluorescence were applied to human skin, and Calcium Green 5N was used as a counterstain. Dimethyl sulfoxide (DMSO) and ethanol were used as alternative vehicles for NPs. Tape stripping was utilized as a barrier-damaged skin model. Skin biopsies dosed with NPs were incubated at 4°C or 37°C for 24 hours and imaged using confocal laser scanning microscopy. NPs were localized in the stratum corneum (SC) and hair follicles without penetrating the epidermis/dermis. Barrier alteration with tape stripping and change in incubation temperature did not induce deeper penetration. DMSO enhanced NP SC penetration but ethanol did not. Except with DMSO vehicle, these hydrolyzed polystyrene NPs did not penetrate intact or barrier-damaged human "viable" epidermis. For further clinical relevance, in vivo human skin studies and more sensitive analytic chemical methodology are suggested.

Ethanol as an inducer of apoptotic process in cheek mucosae in rats

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Katarzyna Borowska

2017-11-01

Full Text Available Apoptosis is the process that plays a important role in development and tissue homeostasis. This physiological process is regulated by caspases. The caspases are specific cysteine proteases. The aim of this study was to prove how ethanol induces apoptotic process in cheek mucosae cells in rats. Fifteen male Wistar rats were used in the research. They were divided into two treated groups (group A and group Abis and control group. The biggest histological changes of cheek mucosae was observed in group with ethanol four weeks after last consumption. There is no indication of ability to regeneration in short time after treatment. The most marked was expression of caspase 8 in group A bis. In caspase 9 expression group A was more visible.

Ethanol wet-bonding technique sensitivity assessed by AFM.

Science.gov (United States)

Osorio, E; Toledano, M; Aguilera, F S; Tay, F R; Osorio, R

2010-11-01

In ethanol wet bonding, water is replaced by ethanol to maintain dehydrated collagen matrices in an extended state to facilitate resin infiltration. Since short ethanol dehydration protocols may be ineffective, this study tested the null hypothesis that there are no differences in ethanol dehydration protocols for maintaining the surface roughness, fibril diameter, and interfibrillar spaces of acid-etched dentin. Polished human dentin surfaces were etched with phosphoric acid and water-rinsed. Tested protocols were: (1) water-rinse (control); (2) 100% ethanol-rinse (1-min); (3) 100% ethanol-rinse (5-min); and (4) progressive ethanol replacement (50-100%). Surface roughness, fibril diameter, and interfibrillar spaces were determined with atomic force microscopy and analyzed by one-way analysis of variance and the Student-Newman-Keuls test (α = 0.05). Dentin roughness and fibril diameter significantly decreased when 100% ethanol (1-5 min) was used for rinsing (p ethanol produced collapse and shrinkage of collagen fibrils. Ascending ethanol concentrations did not collapse the matrix and shrank the fibrils less than absolute ethanol-rinses.

Chronic ethanol exposure induces SK-N-SH cell apoptosis by increasing N-methyl-D-aspartic acid receptor expression and intracellular calcium.

Science.gov (United States)

Wang, Hongbo; Wang, Xiaolong; Li, Yan; Yu, Hao; Wang, Changliang; Feng, Chunmei; Xu, Guohui; Chen, Jiajun; You, Jiabin; Wang, Pengfei; Wu, Xu; Zhao, Rui; Zhang, Guohua

2018-04-01

It has been identified that chronic ethanol exposure damages the nervous system, particularly neurons. There is scientific evidence suggesting that neuronal loss caused by chronic ethanol exposure has an association with neuron apoptosis and intracellular calcium oscillation is one of the primary inducers of apoptosis. Therefore, the present study aimed to investigate the inductive effects of intracellular calcium oscillation on apoptosis in SK-N-SH human neuroblastoma cells and the protective effects of the N-methyl-D-aspartic acid receptor (NMDAR) antagonist, memantine, on SK-N-SH cell apoptosis caused by chronic ethanol exposure. SK-N-SH cells were treated with 100 mM ethanol and memantine (4 µM) for 2 days. Protein expression of NR1 was downregulated by RNA interference (RNAi). Apoptosis was detected by Annexin V/propidium iodide (PI) double-staining and flow cytometry and cell viability was detected using an MTS kit. Fluorescence dual wavelength spectrophotometry was used to determine the intracellular calcium concentration and the levels of NR1 and caspase-3 were detected using western blotting. NR1 mRNA levels were also detected using qPCR. It was found that chronic ethanol exposure reduced neuronal cell viability and caused apoptosis of SK-N-SH cells, and the extent of damage in SK-N-SH cells was associated with ethanol exposure concentration and time. In addition, chronic ethanol exposure increased the concentration of intracellular calcium in SK-N-SH cells by inducing the expression of NMDAR, resulting in apoptosis, and memantine treatment reduced ethanol-induced cell apoptosis. The results of the present study indicate that the application of memantine may provide a novel strategy for the treatment of alcoholic dementia.

The Protective Role of Zinc Sulphate on Ethanol -Induced Liver and Kidney Damages in Rats

International Nuclear Information System (INIS)

Al-Damegh, Mona Abdalla

2007-01-01

Around the world more and more people suffer from alcoholism. Addiction problems, alcoholism and excessive use of drugs both medical and nonmedical, are major causes of liver and kidney damage in adults. The purpose of this study was to investigate on the protective role of zinc sulphate on liver and kidney in rats with acute alcoholism. Wistar albino rats were divided into four groups. Group I; control group, group 2; given only Zinc Sulphate (100 mg/kg/day for 3days), group 3; rats given absolute ethanol (1 ml of absolute ethanol administrated by gavage technique to each rat), group 4 given Zinc sulphate prior to the administration of absolute ethanol. The results of this study revealed that acute ethanol exposure caused degenerative morphological changes in the liver and kidney. Significant difference were found in the levels of serum, liver, kidney super oxide dismutase(SOD), catalase (CAT), nitric oxide(NO), and malondialdehyde (MDA) in the ethanol group compared to the control group. Moreover ,serum urea, creatnine, uric acid, alkaline phoshpatase and transaminases activities (GOTand GPT) were increased in the ethanol group compared to the control group. On the other hand,administration of zinc sulphate in the ethanol group caused a significant decrease in the degenerative changes, lipid peroxidation, antioxidant enzymes, and nitric oxide in serum, liver, and kidney. It can be concluded that zinc Sulphate has a protective role on the ethanol induced liver and kidney injury. In addition ,nitric oxide is involved in the mechanism of acute alcohol intoxication. (author)

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

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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.

Development of Ethanol Withdrawal-Related Sensitization and Relapse Drinking in Mice Selected for High or Low Ethanol Preference

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Lopez, Marcelo F.; Grahame, Nicholas J.; Becker, Howard C.

2010-01-01

Background Previous studies have shown that high alcohol consumption is associated with low withdrawal susceptiblility, while at the same time, other studies have shown that exposure to ethanol vapor increases alcohol drinking in rats and mice. In the present studies, we sought to shed light on this seeming contradiction by using mice selectively bred for High- (HAP) and Low- (LAP) Alcohol Preference, first, assessing these lines for differences in signs of ethanol withdrawal and second, for differences in the efficacy of intermittent alcohol vapor exposure on elevating subsequent ethanol intake. Methods Experiment 1 examined whether these lines of mice differed in ethanol withdrawal-induced CNS hyperexcitability and the development of sensitization to this effect following intermittent ethanol vapor exposure. Adult HAP and LAP lines (replicates 1 and 2), and the C3H/HeNcr inbred strain (included as a control genotype for comparison purposes) received intermittent exposure to ethanol vapor and were evaluated for ethanol withdrawal-induced seizures assessed by scoring handling-induced convulsions (HIC). Experiment 2 examined the influence of chronic intermittent ethanol exposure on voluntary ethanol drinking. Adult male and female HAP-2 and LAP-2 mice, along with male C57BL/6J (included as comparative controls) were trained to drink 10% ethanol using a limited access (2 hr/day) 2-bottle choice paradigm. After stable baseline daily intake was established, mice received chronic intermittent ethanol vapor exposure in inhalation chambers. Ethanol intake sessions resumed 72 hr after final ethanol (or air) exposure for 5 consecutive days. Results Following chronic ethanol treatment, LAP mice exhibited overall greater withdrawal seizure activity compared to HAP mice. In Experiment 2, chronic ethanol exposure/withdrawal resulted in a significant increase in ethanol intake in male C57BL/6J, and modestly elevated intake in HAP-2 male mice. Ethanol intake for male control mice

Grapefruit-seed extract attenuates ethanol-and stress-induced gastric lesions via activation of prostaglandin, nitric oxide and sensory nerve pathways.

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Brzozowski, Tomasz; Konturek, Peter C; Drozdowicz, Danuta; Konturek, Stanislaw J; Zayachivska, Oxana; Pajdo, Robert; Kwiecien, Slawomir; Pawlik, Wieslaw W; Hahn, Eckhart G

2005-11-07

Grapefruit-seed extract (GSE) containing flavonoids, possesses antibacterial and antioxidative properties but whether it influences the gastric defense mechanism and gastroprotection against ethanol- and stress-induced gastric lesions remains unknown. We compared the effects of GSE on gastric mucosal lesions induced in rats by topical application of 100% ethanol or 3.5 h of water immersion and restraint stress (WRS) with or without (A) inhibition of cyclooxygenase (COX)-1 activity by indomethacin and rofecoxib, the selective COX-2 inhibitor, (B) suppression of NO-synthase with L-NNA (20 mg/kg ip), and (C) inactivation by capsaicin (125 mg/kg sc) of sensory nerves with or without intragastric (ig) pretreatment with GSE applied 30 min prior to ethanol or WRS. One hour after ethanol and 3.5 h after the end of WRS, the number and area of gastric lesions were measured by planimetry, the gastric blood flow (GBF) was assessed by H2-gas clearance technique and plasma gastrin levels and the gastric mucosal generation of PGE2, superoxide dismutase (SOD) activity and malonyldialdehyde (MDA) concentration, as an index of lipid peroxidation were determined. Ethanol and WRS caused gastric lesions accompanied by the significant fall in the GBF and SOD activity and the rise in the mucosal MDA content. Pretreatment with GSE (8-64 mg/kg i g) dose-dependently attenuated gastric lesions induced by 100% ethanol and WRS; the dose reducing these lesions by 50% (ID50) was 25 and 36 mg/kg, respectively, and this protective effect was similar to that obtained with methyl PGE2 analog (5 microg/kg i g). GSE significantly raised the GBF, mucosal generation of PGE2, SOD activity and plasma gastrin levels while attenuating MDA content. Inhibition of PGE2 generation with indomethacin or rofecoxib and suppression of NO synthase by L-NNA or capsaicin denervation reversed the GSE-induced protection and the accompanying hyperemia. Co-treatment of exogenous calcitonine gene-related peptide (CGRP) with

Concomitant stress potentiates the preference for, and consumption of, ethanol induced by chronic pre-exposure to ethanol

OpenAIRE

G. Morais-Silva; J. Fernandes-Santos; D. Moreira-Silva; M.T. Marin

2016-01-01

Ethanol abuse is linked to several acute and chronic injuries that can lead to health problems. Ethanol addiction is one of the most severe diseases linked to the abuse of this drug. Symptoms of ethanol addiction include compulsive substance intake and withdrawal syndrome. Stress exposure has an important role in addictive behavior for many drugs of abuse (including ethanol), but the consequences of stress and ethanol in the organism when these factors are concomitant results in a complex int...

Industrial antifoam agents impair ethanol fermentation and induce stress responses in yeast cells.

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Nielsen, Jens Christian; Senne de Oliveira Lino, Felipe; Rasmussen, Thomas Gundelund; Thykær, Jette; Workman, Christopher T; Basso, Thiago Olitta

2017-11-01

The Brazilian sugarcane industry constitutes one of the biggest and most efficient ethanol production processes in the world. Brazilian ethanol production utilizes a unique process, which includes cell recycling, acid wash, and non-aseptic conditions. Process characteristics, such as extensive CO 2 generation, poor quality of raw materials, and frequent contaminations, all lead to excessive foam formation during fermentations, which is treated with antifoam agents (AFA). In this study, we have investigated the impact of industrial AFA treatments on the physiology and transcriptome of the industrial ethanol strain Saccharomyces cerevisiae CAT-1. The investigated AFA included industrially used AFA acquired from Brazilian ethanol plants and commercially available AFA commonly used in the fermentation literature. In batch fermentations, it was shown that industrial AFA compromised growth rates and glucose uptake rates, while commercial AFA had no effect in concentrations relevant for defoaming purposes. Industrial AFA were further tested in laboratory scale simulations of the Brazilian ethanol production process and proved to decrease cell viability compared to the control, and the effects were intensified with increasing AFA concentrations and exposure time. Transcriptome analysis showed that AFA treatments induced additional stress responses in yeast cells compared to the control, shown by an up-regulation of stress-specific genes and a down-regulation of lipid biosynthesis, especially ergosterol. By documenting the detrimental effects associated with chemical AFA, we highlight the importance of developing innocuous systems for foam control in industrial fermentation processes.

PARP Inhibition Prevents Ethanol-Induced Neuroinflammatory Signaling and Neurodegeneration in Rat Adult-Age Brain Slice Cultures

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Tajuddin, Nuzhath; Kim, Hee-Yong

2018-01-01

Using rat adult-age hippocampal-entorhinal cortical (HEC) slice cultures, we examined the role of poly [ADP-ribose] polymerase (PARP) in binge ethanol’s brain inflammatory and neurodegenerative mechanisms. Activated by DNA strand breaks, PARP (principally PARP1 in the brain) promotes DNA repair via poly [ADP-ribose] (PAR) products, but PARP overactivation triggers regulated neuronal necrosis (e.g., parthanatos). Previously, we found that brain PARP1 levels were upregulated by neurotoxic ethanol binges in adult rats and HEC slices, and PARP inhibitor PJ34 abrogated slice neurodegeneration. Binged HEC slices also exhibited increased Ca+2-dependent phospholipase A2 (PLA2) isoenzymes (cPLA2 IVA and sPLA2 IIA) that mobilize proinflammatory ω6 arachidonic acid (ARA). We now find in 4-day–binged HEC slice cultures (100 mM ethanol) that PARP1 elevations after two overnight binges precede PAR, cPLA2, and sPLA2 enhancements by 1 day and high-mobility group box-1 (HMGB1), an ethanol-responsive alarmin that augments proinflammatory cytokines via toll-like receptor-4 (TLR4), by 2 days. After verifying that PJ34 effectively blocks PARP activity (↑PAR), we demonstrated that, like PJ34, three other PARP inhibitors—olaparib, veliparib, and 4-aminobenzamide—provided neuroprotection from ethanol. Importantly, PJ34 and olaparib also prevented ethanol’s amplification of the PLA2 isoenzymes, and two PLA2 inhibitors were neuroprotective—thus coupling PARP to PLA2, with PLA2 activity promoting neurodegeneration. Also, PJ34 and olaparib blocked ethanol-induced HMGB1 elevations, linking brain PARP induction to TLR4 activation. The results provide evidence in adult brains that induction of PARP1 may mediate dual neuroinflammatory pathways (PLA2→phospholipid→ARA and HMGB1→TLR4→proinflammatory cytokines) that are complicit in binge ethanol-induced neurodegeneration. PMID:29339456

Acute ethanol exposure inhibits silencing of cerebellar Golgi cell firing induced by granule cell axon input

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Paolo eBotta

2014-02-01

Full Text Available Golgi cells (GoCs are specialized interneurons that provide inhibitory input to granule cells in the cerebellar cortex. GoCs are pacemaker neurons that spontaneously fire action potentials, triggering spontaneous inhibitory postsynaptic currents in granule cells and also contributing to the generation tonic GABAA receptor-mediated currents in granule cells. In turn, granule cell axons provide feedback glutamatergic input to GoCs. It has been shown that high frequency stimulation of granule cell axons induces a transient pause in GoC firing in a type 2-metabotropic glutamate receptor (mGluR2-dependent manner. Here, we investigated the effect ethanol on the pause of GoC firing induced by high frequency stimulation of granule cell axons. GoC electrophysiological recordings were performed in parasagittal cerebellar vermis slices from postnatal day 23 to 26 rats. Loose-patch cell-attached recordings revealed that ethanol (40 mM reversibly decreases the pause duration. An antagonist of mGluR2 reduced the pause duration but did not affect the effect of ethanol. Whole-cell voltage-clamp recordings showed that currents evoked by an mGluR2 agonist were not significantly affected by ethanol. Perforated-patch experiments in which hyperpolarizing and depolarizing currents were injected into GoCs demonstrated that there is an inverse relationship between spontaneous firing and pause duration. Slight inhibition of the Na+/K+ pump mimicked the effect of ethanol on pause duration. In conclusion, ethanol reduces the granule cell axon-mediated feedback mechanism by reducing the input responsiveness of GoCs. This would result in a transient increase of GABAA receptor-mediated inhibition of granule cells, limiting information flow at the input stage of the cerebellar cortex.

Antidiabetic activities of aqueous ethanol and n-butanol fraction of Moringa stenopetala leaves in streptozotocin-induced diabetic rats.

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Toma, Alemayehu; Makonnen, Eyasu; Mekonnen, Yelamtsehay; Debella, Asfaw; Adisakwattana, Sirichai

2015-07-18

Moringa stenopetala has been used in traditional health systems to treat diabetes mellitus. The aim of this study was to investigate the antidiabetic activity of aqueous ethanol and n-butanol fraction of Moringa stenopetala leaves in streptozotocin (STZ) induced diabetic rats. The aqueous ethanol extract and n-butanol fraction of Moringa stenopetala leaves hydroalcoholic (500 mg/kg body weight) and metformin (150 mg/kg body weight) were administered to diabetic rats. Blood glucose, lipid profiles, liver and kidney function were examined after 14 days of experiment. Histopathological profile of the pancreas was also observed in diabetic rats at the end of study. An oral sucrose challenge test was also carried out to assess the post prandial effect of the extract. Oral administration of the aqueous ethanol and n-butanol extracts of Moringa stenopetala leaves (500 mg/kg body weight) and metformin (150 mg/kg) significantly reduced blood glucose level (PMoringa stenopetala leaves possess antihyperglycemic and antihyperlipidemic properties, and alleviate STZ-induced pancreatic damage in diabetic rats. The beneficial effects of plant material in inhibition of diabetes-induced complications are being investigated.

Effects of Ethanol on the Cerebellum: Advances and Prospects.

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Luo, Jia

2015-08-01

Alcohol abuse causes cerebellar dysfunction and cerebellar ataxia is a common feature in alcoholics. Alcohol exposure during development also impacts the cerebellum. Children with fetal alcohol spectrum disorder (FASD) show many symptoms associated specifically with cerebellar deficits. However, the cellular and molecular mechanisms are unclear. This special issue discusses the most recent advances in the study of mechanisms underlying alcoholinduced cerebellar deficits. The alteration in GABAA receptor-dependent neurotransmission is a potential mechanism for ethanol-induced cerebellar dysfunction. Recent advances indicate ethanol-induced increases in GABA release are not only in Purkinje cells (PCs), but also in molecular layer interneurons and granule cells. Ethanol is shown to disrupt the molecular events at the mossy fiber - granule cell - Golgi cell (MGG) synaptic site and granule cell parallel fibers - PCs (GPP) synaptic site, which may be responsible for ethanol-induced cerebellar ataxia. Aging and ethanol may affect the smooth endoplasmic reticulum (SER) of PC dendrites and cause dendritic regression. Ethanol withdrawal causes mitochondrial damage and aberrant gene modifications in the cerebellum. The interaction between these events may result in neuronal degeneration, thereby contributing to motoric deficit. Ethanol activates doublestranded RNA (dsRNA)-activated protein kinase (PKR) and PKR activation is involved ethanolinduced neuroinflammation and neurotoxicity in the developing cerebellum. Ethanol alters the development of cerebellar circuitry following the loss of PCs, which could result in modifications of the structure and function of other brain regions that receive cerebellar inputs. Lastly, choline, an essential nutrient is evaluated for its potential protection against ethanol-induced cerebellar damages. Choline is shown to ameliorate ethanol-induced cerebellar dysfunction when given before ethanol exposure.

Possible anti-diarrhoeal potential of ethanol leaf extract of Chromolaena odorata in castor oil-induced rats.

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Aba, Patrick Emeka; Joshua, Parker Elija; Ezeonuogu, Francis Chimaobi; Ezeja, Maxwell Ikechukwu; Omoja, Valentine Uneojo; Umeakuana, Paschal Ugochukwu

2015-12-01

Chromolaena odorata is a plant commonly used traditionally to treat ailments including diarrhoea in Nigeria. The ethanol leaf extract of C. odorata was studied for its anti-diarrhoeal activity using electrolyte test and castor oil-induced diarrhoea rats' models. Acute toxicity effect of the extract was also evaluated. The extract showed a dose-dependent protection against castor oil-induced diarrhoea at the tested doses (200 and 400 mg/kg body weights). The protection offered by pretreatment with 400 mg/kg body weight of the ethanol leaf extract of C. odorata with regards to reductions in the incidences of faecal wetness and rate of defaecations were statistically comparable to that achieved with Lomotil, a known anti-diarrhoeic drug. The result of the electrolyte test showed that the extract pretreated groups had significantly (p<0.05) lower potassium and sodium ions in their intestinal fluid when compared with the diarrhoeic untreated controls. This is well tolerated. The results indicate that the ethanol leaf extract of C. odorata is safe and possesses anti-diarrhoeal activity with electrolyte reabsorption proposed as the possible mechanism of action.

Methyl and isopropyl N-methylanthranilates attenuate diclofenac- and ethanol-induced gastric lesions in rats.

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Radulović, Niko S; Jovanović, Ivan; Ilić, Ivan R; Randjelović, Pavle J; Stojanović, Nikola M; Miltojević, Ana B

2013-11-19

Two natural alkaloids, methyl (M) and isopropyl (I) N-methylanthranilates, with recently demonstrated significant pharmacological activities, were assayed for their possible overall effect on intact gastric mucosa and their protective properties towards the onset of gastric lesions induced by diclofenac (a non-steroidal anti-inflammatory drug, NSAID) or ethanol. The influence of I and M on gastric mucosa integrity was assessed by oral administration in doses of 200mg/kg. The gastroprotective action of I and M in doses of 50, 100 and 200mg/kg was analyzed in the diclofenac and ethanol-induced gastric lesion models in rats. After the treatment, the stomachs of the animals were analyzed (captured by a digital camera). Ulcer scoring, morphometric and histopathological analyses of the stomachs were done. The oral application of these compounds on their own, even in quite high doses (200mg/kg) did not induce gastric lesions. Both alkaloids exerted a very strong antiulcer activity, even in low doses (50mg/kg), by decreasing the number of lesions caused by the application of either diclofenac or ethanol, eliminating them completely or reducing them to a form of mucosal hyperemia. Their possible mechanism of action was discussed and due to their many positive properties including anxiolytic, antidepressant, antinociceptive, anti-inflammatory and gastroprotective activities, as well as a cheap and simple synthetic route for their preparation, methyl and isopropyl N-methylanthranilates, both alike, might represent a cost effective alternative sought for in the treatment of peptic ulcers and/or new safer NSAIDs for pain management. © 2013.

Protective effect of Allium neapolitanum Cyr. versus Allium sativum L. on acute ethanol-induced oxidative stress in rat liver.

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Nencini, Cristina; Franchi, Gian Gabriele; Cavallo, Federica; Micheli, Lucia

2010-04-01

This study investigated the protective effect of Allium neapolitanum Cyr., a spontaneous species of the Italian flora, compared with garlic (Allium sativum L.) on liver injury induced by ethanol in rats. Male albino Wistar rats were orally treated with fresh Allium homogenates (leaves or bulbs, 250 mg/kg) daily for 5 days, whereas controls received vehicle only. At the end of the experimental 5-day period, the animals received an acute ethanol dose (6 mL/kg, i.p.) 2 hours before the last Allium administration and were sacrificed 6 hours after ethanol administration. The activities of catalase (CAT), superoxide dismutase (SOD), and glutathione reductase (GR) and the levels of malondialdehyde (MDA), ascorbic acid (AA), and reduced (GSH) and oxidized glutathione in liver tissue were determined. Administration of both Allium species for 5 days (leaves or bulbs) led to no statistical variation of nonenzymatic parameters versus the control group; otherwise Allium treatment caused an increase of GSH and AA levels compared with the ethanol group and a diminution of MDA levels, showing in addition that A. neapolitanum bulb had the best protective effect. Regarding to enzymatic parameters, GR and CAT activities were enhanced significantly compared with the ethanol group, whereas SOD activity showed a trend different from other parameters estimated. However, the treatment with both Allium species followed by acute ethanol administration reestablished the nonenzymatic parameters similar to control values and enhanced the activities of the enzymes measured. These results suggest that fresh Allium homogenates (leaves or bulbs) possess antioxidant properties and provide protection against ethanol-induced liver injury.

Increases in anxiety-like behavior induced by acute stress are reversed by ethanol in adolescent but not adult rats.

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Varlinskaya, Elena I; Spear, Linda P

2012-01-01

Repeated exposure to stressors has been found to increase anxiety-like behavior in laboratory rodents, with the social anxiety induced by repeated restraint being extremely sensitive to anxiolytic effects of ethanol in both adolescent and adult rats. No studies, however, have compared social anxiogenic effects of acute stress or the capacity of ethanol to reverse this anxiety in adolescent and adult animals. Therefore, the present study was designed to investigate whether adolescent [postnatal day (P35)] Sprague-Dawley rats differ from their adult counterparts (P70) in the impact of acute restraint stress on social anxiety and in their sensitivity to the social anxiolytic effects of ethanol. Animals were restrained for 90 min, followed by examination of stress- and ethanol-induced (0, 0.25, 0.5, 0.75, and 1 g/kg) alterations in social behavior using a modified social interaction test in a familiar environment. Acute restraint stress increased anxiety, as indexed by reduced levels of social investigation at both ages, and decreased social preference among adolescents. These increases in anxiety were dramatically reversed among adolescents by acute ethanol. No anxiolytic-like effects of ethanol emerged following restraint stress in adults. The social suppression seen in response to higher doses of ethanol was reversed by restraint stress in animals of both ages. To the extent that these data are applicable to humans, the results of the present study provide some experimental evidence that stressful life events may increase the attractiveness of alcohol as an anxiolytic agent for adolescents. Copyright © 2011 Elsevier Inc. All rights reserved.

Influence of ethanol admixture on the determination of equivalence ratios in DISI engines by laser-induced fluorescence.

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Storch, Michael; Lind, Susanne; Will, Stefan; Zigan, Lars

2016-10-20

In this work, the planar laser-induced fluorescence of a fuel tracer is applied for the analysis of mixture formation for various ethanol/iso-octane blends in a direct-injection spark-ignition (DISI) engine. The tracer triethylamine (TEA) was added to pure iso-octane and ethanol as well as to their blends E20 and E85 for the measurement of the fuel/air ratio. In general, ethanol blending strongly affects the mixture formation process, which is caused by specific physical fuel properties influencing the evaporation process of ethanol in comparison to iso-octane. As interactions of the fuel and tracer fluorescence appear possible, TEA fluorescence was studied for different fuel blends in a cuvette, in a calibration cell under constant conditions, and in an optically accessible internal combustion engine at late injection timing. It was found that ethanol blending strongly affects the fluorescence intensity of TEA in the liquid phase, which can be explained by the interaction of the tracer and ethanol molecules. However, in the gas phase a quantification of the fuel/air ratio is possible for different ethanol fuel blends, which is demonstrated in a DISI engine. Under stratified charge conditions the engine results showed a significant impact of a high amount of ethanol on the mixture formation process, leading to a leaner mixture in comparison to iso-octane.

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

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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.

Gastroprotective Effect of Ethanolic Extract of Curcuma xanthorrhiza Leaf against Ethanol-Induced Gastric Mucosal Lesions in Sprague-Dawley Rats

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Nurhidayah Ab. Rahim

2014-01-01

Full Text Available Herbal medicines appeared promising in prevention of many diseases. This study was conducted to investigate the gastroprotective effect of Curcuma xanthorrhiza leaf in the rats induced gastric ulcer by ethanol. Normal and ulcer control received carboxymethycellulose (5 mL/kg orally, positive control was administered with 20 mg/kg omeprazole (reference drug and 2 groups were received 250 mg/kg and 500 mg/kg of the leaf extract, respectively. To induce of gastric ulcers formation, ethanol (5 mL/kg was given orally to all groups except normal control. Gross ulcer areas, histology, and amount of prostaglandin E2, superoxide dismutase and malondialdehyde were assessed to determine the potentiality of extract in prevention against gastric ulcers. Oral administration of extract showed significant gastric protection effect as the ulcer areas was remarkably decreased. Histology observation showed less edema and leucocytes infiltration as compared with the ulcer control which exhibited severe gastric mucosa injury. Furthermore, the leaf extract elevated the mucus weight, level of prostaglandin E2 and superoxide dismutase. The extract also reduced malondialdehyde amount significantly. Results showed leaf extract of Curcuma xanthorrhiza can enhanced the gastric protection and sustained the integrity of gastric mucosa structure. Acute toxicity test did not showed any sign of toxicity (2 g/kg and 5 g/kg.

Prevention of experimentally-induced gastric ulcers in rats by an ethanolic extract of "Parsley" Petroselinum crispum.

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Al-Howiriny, Tawfeq; Al-Sohaibani, Mohammed; El-Tahir, Kamal; Rafatullah, Syed

2003-01-01

An ethanolic extract of Parsley, Petroselinum crispum (Mill.) Nym.ex A.W. Hill (Umbelliferae), was tested for its ability to inhibit gastric secretion and to protect gastric mucosa against the injuries caused by pyloric ligation, hypothermic restraint stress, indomethacin and cytodestructive agents (80% ethanol, 0.2 M NaOH and 25% NaCl) in rats. The extract in doses of 1 and 2 g/kg body weight had a significant antiulcerogenic activity on the models used. Besides, ethanol-induced depleted gastric wall mucus and non-protein sulfhydryl contents were replenished by pretreatment with Parsley extract. Acute toxicity tests showed a large margin of safety for the extract. The phytochemical screening of Parsley leaves revealed the presence of tannins, flavonoids, sterols and/or triterpenes.

Ethanol-induced increase in portal blood flow: Role of acetate and A1- and A2-adenosine receptors

International Nuclear Information System (INIS)

Carmichael, F.J.; Saldivia, V.; Varghese, G.A.; Israel, Y.; Orrego, H.

1988-01-01

The increase in portal blood flow induced by ethanol appears to be adenosine mediated. Acetate, which is released by the liver during ethanol metabolism, is known to increase adenosine levels in tissues and in blood. The effects of acetate on portal blood flow were investigated in rats using the microsphere technique. The intravenous infusion of acetate resulted in vasodilation of the preportal vasculature and in a dose-dependent increase in portal blood flow. This acetate-induced increase in portal blood flow was suppressed by the adenosine receptor blocker, 8-phenyltheophylline. Using the A 1 -adenosine receptor agonist N-6-cyclohexyl adenosine and the A 2 -agonist 5'-N-ethylcarboxamido adenosine, we demonstrate that the effect of adenosine on the preportal vasculature is mediated by the A 2 -subtype of adenosine receptors. In conclusion, these data support the hypothesis that the increase in portal blood flow after ethanol administration results from a preportal vasodilatory effect of adenosine formed from acetate metabolism in extrahepatic tissues

Ethanol extract from portulaca oleracea L. attenuated acetaminophen-induced mice liver injury

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Liu, Xue-Feng; Zheng, Cheng-Gang; Shi, Hong-Guang; Tang, Gu-Sheng; Wang, Wan-Yin; Zhou, Juan; Dong, Li-Wei

2015-01-01

Acetaminophen-induced liver injury represents the most frequent cause of drug-induced liver failure in the world. Portulaca oleracea L., a widely distributed weed, has been used as a folk medicine in many countries. Previously, we reported that the ethanol extracts of Portulaca oleracea L. (PO) exhibited significant anti-hypoxic activity. In the present study, we investigated the role of PO on acetaminophen (APAP) induced hepatotoxicity. The results demonstrated that PO was an effective anti-oxidative agent, which could, to some extent, reverse APAP-induced hepatotoxicity by regulating the reactive oxygen species (ROS) in the liver of mice. At the same time, PO treatment significantly decreased mice serum levels of IL-6 and TNFα and their mRNA expression in liver tissue IL-α and TNFα play an important role during APAP-induced liver injury. Furthermore, PO inhibited APAP and TNFα-induced activation of JNK, whose activation play an important effect during APAP induced liver injury. These findings suggested that administration of PO may be an effective strategy to prevent or treat liver injury induced by APAP. PMID:25901199

Confocal laser scanning microscopy to estimate nanoparticles’ human skin penetration in vitro

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Elmahdy, Akram; Cao, Yachao; Hui, Xiaoying; Maibach, Howard

2017-01-01

Objective With rapid development of nanotechnology, there is increasing interest in nanoparticle (NP) application and its safety and efficacy on human skin. In this study, we utilized confocal laser scanning microscopy to estimate NP skin penetration. Methods Three different-sized polystyrene NPs marked with red fluorescence were applied to human skin, and Calcium Green 5N was used as a counterstain. Dimethyl sulfoxide (DMSO) and ethanol were used as alternative vehicles for NPs. Tape stripping was utilized as a barrier-damaged skin model. Skin biopsies dosed with NPs were incubated at 4°C or 37°C for 24 hours and imaged using confocal laser scanning microscopy. Results NPs were localized in the stratum corneum (SC) and hair follicles without penetrating the epidermis/dermis. Barrier alteration with tape stripping and change in incubation temperature did not induce deeper penetration. DMSO enhanced NP SC penetration but ethanol did not. Conclusion Except with DMSO vehicle, these hydrolyzed polystyrene NPs did not penetrate intact or barrier-damaged human “viable” epidermis. For further clinical relevance, in vivo human skin studies and more sensitive analytic chemical methodology are suggested. PMID:29184403

Prevention of ethanol-induced vascular injury and gastric mucosal lesions by sucralfate and its components: possible role of endogenous sulfhydryls

Energy Technology Data Exchange (ETDEWEB)

Szabo, S.; Brown, A.

1987-09-01

The authors tested the hypothesis that sucralfate, which contains eight sulfate and aluminum molecules on a sucrose and its other components might decrease ethanol-induced vascular injury and hemorrhagic mucosal lesions through a sulfhydryl (SH)-sensitive process. Experiments performed in rats revealed that the entire sucralfate molecule is not a prerequisite for protection against ethanol-induced mucosal vascular injury and erosions. It appears that sulfate and sucrose octasulfate are potent components of sucralfate, although an equimolar amount of sucralfate is at least twice as effective in gastroprotection than its components. The SH alkylator N-ethylmaleimide abolished the gastroprotection by sucralfate, suggesting SH-sensitive process in the mucosal protection which seems to be associated with the prevention of rapidly developing vascular injury in the stomach of rats given ethanol.

The interplay between ventro striatal BDNF levels and the effects of valproic acid on the acquisition of ethanol-induced conditioned place preference in mice.

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Dos Santos, Manuel Alves; Escudeiro, Sarah Sousa; Vasconcelos, Germana Silva; Matos, Natália Castelo Branco; de Souza, Marcos Romário Matos; Patrocínio, Manoel Cláudio Azevedo; Dantas, Leonardo Pimentel; Macêdo, Danielle; Vasconcelos, Silvânia Maria Mendes

2017-11-01

Alcohol addiction is a chronic, relapsing and progressive brain disease with serious consequences for health. Compulsive use of alcohol is associated with the capacity to change brain structures involved with the reward pathway, such as ventral striatum. Recent evidence suggests a role of chromatin remodeling in the pathophysiology of alcohol dependence and addictive-like behaviors. In addition, neuroadaptive changes mediated by the brain-derived neurotrophic factor (BDNF) seems to be an interesting pharmacological target for alcoholism treatment. In the present study, we evaluated the effects of the deacetylase inhibitor valproic acid (VPA) (300mg/kg) on the conditioned rewarding effects of ethanol using conditioned place preference (CPP) (15% v/v; 2g/kg). Ethanol rewarding effect was investigated using a biased protocol of CPP. BDNF levels were measured in the ventral striatum. Ethanol administration induced CPP. VPA pretreatment did not reduce ethanol-CPP acquisition. VPA pretreatment increased BDNF levels when compared to ethanol induced-CPP. VPA pretreatment increased BDNF levels even in saline conditioned mice. Taken together, our results indicate a modulatory effect of VPA on the BDNF levels in the ventral striatum. Overall, this study brings initial insights into the involvement of neurotrophic mechanisms in the ventral striatum in ethanol-induced addictive-like behavior. Copyright © 2017 Elsevier B.V. All rights reserved.

A pair of dopamine neurons target the D1-like dopamine receptor DopR in the central complex to promote ethanol-stimulated locomotion in Drosophila.

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Eric C Kong

2010-04-01

Full Text Available Dopamine is a mediator of the stimulant properties of drugs of abuse, including ethanol, in mammals and in the fruit fly Drosophila. The neural substrates for the stimulant actions of ethanol in flies are not known. We show that a subset of dopamine neurons and their targets, through the action of the D1-like dopamine receptor DopR, promote locomotor activation in response to acute ethanol exposure. A bilateral pair of dopaminergic neurons in the fly brain mediates the enhanced locomotor activity induced by ethanol exposure, and promotes locomotion when directly activated. These neurons project to the central complex ellipsoid body, a structure implicated in regulating motor behaviors. Ellipsoid body neurons are required for ethanol-induced locomotor activity and they express DopR. Elimination of DopR blunts the locomotor activating effects of ethanol, and this behavior can be restored by selective expression of DopR in the ellipsoid body. These data tie the activity of defined dopamine neurons to D1-like DopR-expressing neurons to form a neural circuit that governs acute responding to ethanol.

Stress Sensitization of Ethanol Withdrawal-Induced Reduction in Social Interaction: Inhibition by CRF-1 and Benzodiazepine Receptor Antagonists and a 5-HT1A-Receptor Agonist

OpenAIRE

Breese, George R; Knapp, Darin J; Overstreet, David H

2004-01-01

Repeated withdrawals from chronic ethanol sensitize the withdrawal-induced reduction in social interaction behaviors. This study determined whether stress might substitute for repeated withdrawals to facilitate withdrawal-induced anxiety-like behavior. When two 1-h periods of restraint stress were applied at 1-week intervals to rats fed control diet, social interaction was reduced upon withdrawal from a subsequent 5-day exposure to ethanol diet. Neither this ethanol exposure alone nor exposur...

Deletion of vanilloid receptor (TRPV1) in mice alters behavioral effects of ethanol

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Blednov, Y.A.; Harris, R.A.

2009-01-01

The vanilloid receptor TRPV1 is activated by ethanol and this may be important for some of the central and peripheral actions of ethanol. To determine if this receptor has a role in ethanol-mediated behaviors, we studied null mutant mice in which the Trpv1 gene was deleted. Mice lacking this gene showed significantly higher preference for ethanol and consumed more ethanol in a two-bottle choice test as compared with wild type littermates. Null mutant mice showed shorter duration of loss of righting reflex induced by low doses of ethanol (3.2 and 3.4 g/kg) and faster recovery from motor incoordination induced by ethanol (2 g/kg). However, there were no differences between null mutant and wild type mice in severity of ethanol-induced acute withdrawal (4 g/kg) or conditioned taste aversion to ethanol (2.5 g/kg). Two behavioral phenotypes (decreased sensitivity to ethanol-induced sedation and faster recovery from ethanol-induced motor incoordination) seen in null mutant mice were reproduced in wild type mice by injection of a TRPV1 antagonist, capsazepine (10 mg/kg). These two ethanol behaviors were changed in the opposite direction after injection of capsaicin, a selective TRPV1 agonist, in wild type mice. The studies provide the first evidence that TRPV1 is important for specific behavioral actions of ethanol. PMID:19705551

Ethanol extract of seeds of Oenothera odorata induces vasorelaxation via endothelium-dependent NO-cGMP signaling through activation of Akt-eNOS-sGC pathway.

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Kim, Hye Yoom; Oh, Hyuncheol; Li, Xiang; Cho, Kyung Woo; Kang, Dae Gill; Lee, Ho Sub

2011-01-27

The vasorelaxant effect of ethanol extract of seeds of Oenothera odorata (Onagraceae) (one species of evening primroses) (ESOO) and its mechanisms involved were defined. Changes in vascular tension, guanosine 3',5'-cyclic monophosphate (cGMP) levels, and Akt expression were measured in carotid arterial rings from rats. Seeds of Oenothera odorata were extracted with ethanol (94%) and the extract was filtered, concentrated and stored at -70°C. ESOO relaxed endothelium-intact, but not endothelium-denuded, carotid arterial rings in a concentration-dependent manner. Similarly, ESOO increased cGMP levels of the carotid arterial rings. Pretreatment of endothelium-intact arterial rings with L-NAME, an inhibitor of nitric oxide synthase (NOS), or ODQ, an inhibitor of soluble guanylyl cyclase (sGC), blocked the ESOO-induced vasorelaxation and increase in cGMP levels. Nominally Ca(2+)-free but not L-typed Ca(2+) channel inhibition attenuated the ESOO-induced vasorelaxation. Thapsigargin, Gd(3+), and 2-aminoethyl diphenylborinate, modulators of store-operated Ca(2+) entry (SOCE), significantly attenuated the ESOO-induced vasorelaxation and increase in cGMP levels. Further, wortmannin, an inhibitor of Akt, attenuated the ESOO-induced vasorelaxation and increases in cGMP levels and phosphorylated Akt2 expression. K(+) channel blockade with TEA, 4-aminopyridine, and glibenclamide attenuated the ESOO-induced vascular relaxation. Taken together, the present study demonstrates that ESOO relaxes vascular smooth muscle via endothelium-dependent NO-cGMP signaling through activation of the Akt-eNOS-sGC pathway. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Ginger extract mitigates ethanol-induced changes of alpha and beta - myosin heavy chain isoforms gene expression and oxidative stress in the heart of male wistar rats.

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Shirpoor, Alireza; Zerehpoosh, Mitra; Ansari, Mohammad Hasan Khadem; Kheradmand, Fatemeh; Rasmi, Yousef

2017-09-01

The association between ethanol consumption and heart abnormalities, such as chamber dilation, myocyte damage, ventricular hypertrophy, and hypertension is well known. However, underlying molecular mediators involved in ethanol-induced heart abnormalities remain elusive. The aim of this study was to investigate the effect of chronic ethanol exposure on alpha and beta - myosin heavy chain (MHC) isoforms gene expression transition and oxidative stress in rats' heart. It was also planned to find out whether ginger extract mitigated the abnormalities induced by ethanol in rats' heart. Male wistar rats were divided into three groups of eight animals as follows: Control, ethanol, and ginger extract treated ethanolic (GETE) groups. After six weeks of treatment, the results revealed a significant increase in the β-MHC gene expression, 8- OHdG amount, and NADPH oxidase level. Furthermore, a significant decrease in the ratio of α-MHC/β-MHC gene expression to the amount of paraoxonase enzyme in the ethanol group compared to the control group was found. The consumption of Ginger extract along with ethanol ameliorated the changes in MHC isoforms gene expression and reduced the elevated amount of 8-OHdG and NADPH oxidase. Moreover, compared to the consumption of ethanol alone, it increased the paraoxonase level significantly. These findings indicate that ethanol-induced heart abnormalities may in part be associated with MHC isoforms changes mediated by oxidative stress, and that these effects can be alleviated by using ginger extract as an antioxidant molecule. Copyright © 2017 Elsevier B.V. All rights reserved.

Autoshaping of ethanol drinking in rats: effects of ethanol concentration and trial spacing.

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Tomie, Arthur; Wong, Karlvin; Apor, Khristine; Patterson-Buckendahl, Patricia; Pohorecky, Larissa A

2003-11-01

In two studies, we evaluated the effects of ethanol concentration and trial spacing on Pavlovian autoshaping of ethanol drinking in rats. In these studies, the brief insertion of an ethanol sipper conditioned stimulus (CS) was followed by the response-independent presentation of food unconditioned stimulus (US), inducing sipper CS-directed drinking conditioned responses (CRs) in all rats. In Experiment 1, the ethanol concentration in the sipper CS [0%-16% volume/volume (vol./vol.), in increments of 1%] was systematically increased within subjects across autoshaping sessions. Groups of rats received sipper CS-food US pairings (Paired/Ethanol), a CS-US random procedure (Random/Ethanol), or water sipper CS paired with food US (Paired/Water). In Experiment 2, saccharin-fading procedures were used to initiate, in the Ethanol group, drinking of 6% (vol./vol.) ethanol in 0.1% saccharin or, in the Water group, drinking of tap water in 0.1% saccharin. After elimination of saccharin, and across days, the duration of access to the sipper CS during each autoshaping trial was increased (5, 10, 12.5, 15, 17.5, and 20 s), and subsequently, across days, the duration of the mean intertrial interval (ITI) was increased (60, 90, 120, and 150 s). In Experiment 1, Paired/Ethanol and Random/Ethanol groups showed higher intake of ethanol, in terms of grams per kilogram of body weight, at higher ethanol concentrations, with more ethanol intake recorded in the Paired/Ethanol group. In Experiment 2, the Ethanol group drank more than was consumed by the Water group, and, for both groups, fluid intake increased with longer ITIs. Results support the suggestion that autoshaping contributes to sipper CS-directed ethanol drinking.

Red sorrel (Hibiscus Sabdariffa) prevents the ethanol-induced deficits of Purkinje cells in the cerebellum.

Science.gov (United States)

Suryanti, S; Partadiredja, G; Atthobari, J

2015-01-01

The present study is aimed at investigating the possible protective effects of H. sabdariffa on ethanol-elicited deficits of motor coordination and estimated total number of the Purkinje cells of the cerebellums of adolescent male Wistar rats. Forty male Wistar rats aged 21 days were divided into five groups. Na/wtr group was given water orally and injected with normal saline intra peritoneally (ip). Eth/wtr group was given water orally and ethanol (ip). Another three experimental groups (Eth/Hsab) were given different dosages of H. sabdariffa and ethanol (ip). All groups were treated intermittently for the total period of treatment of two weeks. The motor coordination of rats was tested prior and subsequent to the treatments. The rats were euthanized, and their cerebellums were examined. The total number of Purkinje cells was estimated using physical fractionator method. Upon revolving drum test, the number of falls of rats increased following ethanol treatment. There was no significant difference between the total number of falls prior and subsequent to treatment in all Eth/Hsab groups. The estimated total number of Purkinje cells in Eth/Hsab groups was higher than in Eth/wtr group. H. sabdariffa may prevent the ethanol-induced deficits of motor coordination and estimated total number of Purkinje cells of the cerebellums in adolescent rats (Tab. 3, Fig. 1, Ref. 42).

The Diagnostic Utility of Induced Sputum Microscopy and Culture in Childhood Pneumonia.

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Murdoch, David R; Morpeth, Susan C; Hammitt, Laura L; Driscoll, Amanda J; Watson, Nora L; Baggett, Henry C; Brooks, W Abdullah; Deloria Knoll, Maria; Feikin, Daniel R; Kotloff, Karen L; Levine, Orin S; Madhi, Shabir A; O'Brien, Katherine L; Scott, J Anthony G; Thea, Donald M; Adrian, Peter V; Ahmed, Dilruba; Alam, Muntasir; Awori, Juliet O; DeLuca, Andrea N; Higdon, Melissa M; Karron, Ruth A; Kwenda, Geoffrey; Machuka, Eunice M; Makprasert, Sirirat; McLellan, Jessica; Moore, David P; Mwaba, John; Mwarumba, Salim; Park, Daniel E; Prosperi, Christine; Sangwichian, Ornuma; Sissoko, Seydou; Tapia, Milagritos D; Zeger, Scott L; Howie, Stephen R C

2017-06-15

Sputum microscopy and culture are commonly used for diagnosing the cause of pneumonia in adults but are rarely performed in children due to difficulties in obtaining specimens. Induced sputum is occasionally used to investigate lower respiratory infections in children but has not been widely used in pneumonia etiology studies. We evaluated the diagnostic utility of induced sputum microscopy and culture in patients enrolled in the Pneumonia Etiology Research for Child Health (PERCH) study, a large study of community-acquired pneumonia in children aged 1-59 months. Comparisons were made between induced sputum samples from hospitalized children with radiographically confirmed pneumonia and children categorized as nonpneumonia (due to the absence of prespecified clinical and laboratory signs and absence of infiltrate on chest radiograph). One induced sputum sample was available for analysis from 3772 (89.1%) of 4232 suspected pneumonia cases enrolled in PERCH. Of these, sputum from 2608 (69.1%) met the quality criterion of <10 squamous epithelial cells per low-power field, and 1162 (44.6%) had radiographic pneumonia. Induced sputum microscopy and culture results were not associated with radiographic pneumonia, regardless of prior antibiotic use, stratification by specific bacteria, or interpretative criteria used. The findings of this study do not support the culture of induced sputum specimens as a diagnostic tool for pneumonia in young children as part of routine clinical practice. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Efficient electron-induced removal of oxalate ions and formation of copper nanoparticles from copper(II oxalate precursor layers

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Kai Rückriem

2016-06-01

Full Text Available Copper(II oxalate grown on carboxy-terminated self-assembled monolayers (SAM using a step-by-step approach was used as precursor for the electron-induced synthesis of surface-supported copper nanoparticles. The precursor material was deposited by dipping the surfaces alternately in ethanolic solutions of copper(II acetate and oxalic acid with intermediate thorough rinsing steps. The deposition of copper(II oxalate and the efficient electron-induced removal of the oxalate ions was monitored by reflection absorption infrared spectroscopy (RAIRS. Helium ion microscopy (HIM reveals the formation of spherical nanoparticles with well-defined size and X-ray photoelectron spectroscopy (XPS confirms their metallic nature. Continued irradiation after depletion of oxalate does not lead to further particle growth giving evidence that nanoparticle formation is primarily controlled by the available amount of precursor.

Prenatal ethanol exposure modifies locomotor activity and induces selective changes in Met-enk expression in adolescent rats.

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Abate, P; Reyes-Guzmán, A C; Hernández-Fonseca, K; Méndez, M

2017-04-01

Several studies suggest that prenatal ethanol exposure (PEE) facilitates ethanol intake. Opioid peptides play a main role in ethanol reinforcement during infancy and adulthood. However, PEE effects upon motor responsiveness elicited by an ethanol challenge and the participation of opioids in these actions remain to be understood. This work assessed the susceptibility of adolescent rats to prenatal and/or postnatal ethanol exposure in terms of behavioral responses, as well as alcohol effects on Met-enk expression in brain areas related to drug reinforcement. Motor parameters (horizontal locomotion, rearings and stereotyped behaviors) in pre- and postnatally ethanol-challenged adolescents were evaluated. Pregnant rats received ethanol (2g/kg) or water during gestational days 17-20. Adolescents at postnatal day 30 (PD30) were tested in a three-trial activity paradigm (habituation, vehicle and drug sessions). Met-enk content was quantitated by radioimmunoassay in several regions: ventral tegmental area [VTA], nucleus accumbens [NAcc], prefrontal cortex [PFC], substantia nigra [SN], caudate-putamen [CP], amygdala, hypothalamus and hippocampus. PEE significantly reduced rearing responses. Ethanol challenge at PD30 decreased horizontal locomotion and showed a tendency to reduce rearings and stereotyped behaviors. PEE increased Met-enk content in the PFC, CP, hypothalamus and hippocampus, but did not alter peptide levels in the amygdala, VTA and NAcc. These findings suggest that PEE selectively modifies behavioral parameters at PD30 and induces specific changes in Met-enk content in regions of the mesocortical and nigrostriatal pathways, the hypothalamus and hippocampus. Prenatal and postnatal ethanol actions on motor activity in adolescents could involve activation of specific neural enkephalinergic pathways. Copyright © 2016 Elsevier Ltd. All rights reserved.

Reversing gastric mucosal alterations during ethanol-induced chronic gastritis in rats by oral administration of Opuntia ficus-indica mucilage

Science.gov (United States)

Vázquez-Ramírez, Ricardo; Olguín-Martínez, Marisela; Kubli-Garfias, Carlos; Hernández-Muñoz, Rolando

2006-01-01

AIM: To study the effect of mucilage obtained from cladodes of Opuntia ficus-indica (Cactaceae) on the healing of ethanol-induced gastritis in rats. METHODS: Chronic gastric mucosa injury was treated with mucilage (5 mg/kg per day) after it was induced by ethanol. Lipid composition, activity of 5’-nucleotidase (a membrane-associated ectoenzyme) and cytosolic activities of lactate and alcohol dehydrogenases in the plasma membrane of gastric mucosa were determined. Histological studies of gastric samples from the experimental groups were included. RESULTS: Ethanol elicited the histological profile of gastritis characterized by loss of the surface epithelium and infiltration of polymorphonuclear leukocytes. Phosphatidylcholine (PC) decreased and cholesterol content increased in plasma membranes of the gastric mucosa. In addition, cytosolic activity increased while the activity of alcohol dehydrogenases decreased. The administration of mucilage promptly corrected these enzymatic changes. In fact, mucilage readily accelerated restoration of the ethanol-induced histological alterations and the disturbances in plasma membranes of gastric mucosa, showing a univocal anti-inflammatory effect. The activity of 5’-nucleotidase correlated with the changes in lipid composition and the fluidity of gastric mucosal plasma membranes. CONCLUSION: The beneficial action of mucilage seems correlated with stabilization of plasma membranes of damaged gastric mucosa. Molecular interactions between mucilage monosaccharides and membrane phospholipids, mainly PC and phosphatidylethanolamine (PE), may be the relevant features responsible for changing activities of membrane-attached proteins during the healing process after chronic gastric mucosal damage. PMID:16865772

Reversing gastric mucosal alterations during ethanol-induced chronic gastritis in rats by oral administration of Opuntia ficus-indica mucilage.

Science.gov (United States)

Vázquez-Ramírez, Ricardo; Olguín-Martínez, Marisela; Kubli-Garfias, Carlos; Hernández-Muñoz, Rolando

2006-07-21

To study the effect of mucilage obtained from cladodes of Opuntia ficus-indica (Cactaceae) on the healing of ethanol-induced gastritis in rats. Chronic gastric mucosa injury was treated with mucilage (5 mg/kg per day) after it was induced by ethanol. Lipid composition, activity of 5'-nucleotidase (a membrane-associated ectoenzyme) and cytosolic activities of lactate and alcohol dehydrogenases in the plasma membrane of gastric mucosa were determined. Histological studies of gastric samples from the experimental groups were included. Ethanol elicited the histological profile of gastritis characterized by loss of the surface epithelium and infiltration of polymorphonuclear leukocytes. Phosphatidylcholine (PC) decreased and cholesterol content increased in plasma membranes of the gastric mucosa. In addition, cytosolic activity increased while the activity of alcohol dehydrogenases decreased. The administration of mucilage promptly corrected these enzymatic changes. In fact, mucilage readily accelerated restoration of the ethanol-induced histological alterations and the disturbances in plasma membranes of gastric mucosa, showing a univocal anti-inflammatory effect. The activity of 5'-nucleotidase correlated with the changes in lipid composition and the fluidity of gastric mucosal plasma membranes. The beneficial action of mucilage seems correlated with stabilization of plasma membranes of damaged gastric mucosa. Molecular interactions between mucilage monosaccharides and membrane phospholipids, mainly PC and phosphatidylethanolamine (PE), may be the relevant features responsible for changing activities of membrane-attached proteins during the healing process after chronic gastric mucosal damage.

Salt-induced square prism Pd microtubes and their ethanol electrocatalysis properties

International Nuclear Information System (INIS)

Jiang, Kunpeng; Ma, Shenghua; Wang, Yinan; Zhang, Ying; Han, Xiaojun

2017-01-01

Highlights: • A simple method is established to fabricate square prism Pd microtubes. • The novel square prism Pd microtubes are based on a salt-induced aggregation event. • The surface of the square prism tubes convert from cataphracted nanosheets to spheres after calcinations treatment. • The square prism pure Pd tubes show excellent electro catalytic activity towards ethanol oxidation. - Abstract: The synthesis of square prism tubes are always challenging due to their thermo and dynamical instability. We demonstrated a simple method using Pd"2"+ doped PoPD oligomers as building blocks to assemble into 1D square prism metal-organic microtubes, which consists of cataphracted nanosheets on the surfaces. After high temperature treatment, the microtubes became square prism Pd tubes with a cross section size of 3 μm. The pure Pd microtubes showed excellent catalyzing activity towards the electro oxidation of ethanol. Their electrochemically active surface area is 48.2 m"2 g"−"1, which indicates the square prism Pd tubes have great potential in the field of fuel cell.

Salt-induced square prism Pd microtubes and their ethanol electrocatalysis properties

Energy Technology Data Exchange (ETDEWEB)

Jiang, Kunpeng; Ma, Shenghua; Wang, Yinan; Zhang, Ying; Han, Xiaojun, E-mail: hanxiaojun@hit.edu.cn

2017-05-01

Highlights: • A simple method is established to fabricate square prism Pd microtubes. • The novel square prism Pd microtubes are based on a salt-induced aggregation event. • The surface of the square prism tubes convert from cataphracted nanosheets to spheres after calcinations treatment. • The square prism pure Pd tubes show excellent electro catalytic activity towards ethanol oxidation. - Abstract: The synthesis of square prism tubes are always challenging due to their thermo and dynamical instability. We demonstrated a simple method using Pd{sup 2+} doped PoPD oligomers as building blocks to assemble into 1D square prism metal-organic microtubes, which consists of cataphracted nanosheets on the surfaces. After high temperature treatment, the microtubes became square prism Pd tubes with a cross section size of 3 μm. The pure Pd microtubes showed excellent catalyzing activity towards the electro oxidation of ethanol. Their electrochemically active surface area is 48.2 m{sup 2} g{sup −1}, which indicates the square prism Pd tubes have great potential in the field of fuel cell.

Aqueous and ethanolic leaf extracts of Ocimum basilicum (sweet basil) protect against sodium arsenite-induced hepatotoxicity in Wistar rats.

Science.gov (United States)

Gbadegesin, M A; Odunola, O A

2010-11-25

We evaluated the effects of aqueous and ethanolic leaf extracts of Ocimum basilicum (sweet basil) on sodium arsenite-induced hepatotoxicity in Wistar rats. We observed that treatment of the animals with the extracts before or just after sodium arsenite administration significantly (p < 0.05) reduced mean liver and serum γ-Glutamyl transferase (γGT), and serum alkaline phosphatase (ALP) activities when compared with the group administered the toxin alone. In addition, treatments of the animals with aqueous or ethanolic extract of O. basilicum before the administration of sodium arsenite resulted in the attenuation of the sodium arsenite-induced aspartate and alanine aminotransferase activities: ALT (from 282.6% to 167.7% and 157.8%), AST (from 325.1% to 173.5% and 164.2%) for the group administered sodium arsenite alone, the aqueous extracts plus sodium arsenite, and ethanolic extracts plus sodium arsenite respectively, expressed as percentage of the negative control. These findings support the presence of hepatoprotective activity in the O.basilicum extracts.

PPARβ/δ modulates ethanol-induced hepatic effects by decreasing pyridoxal kinase activity

International Nuclear Information System (INIS)

Goudarzi, Maryam; Koga, Takayuki; Khozoie, Combiz; Mak, Tytus D.; Kang, Boo-Hyon; Jr, Albert J. Fornace; Peters, Jeffrey M.

2013-01-01

Because of the significant morbidity and lethality caused by alcoholic liver disease (ALD), there remains a need to elucidate the regulatory mechanisms that can be targeted to prevent and treat ALD. Toward this goal, minimally invasive biomarker discovery represents an outstanding approach for these purposes. The mechanisms underlying ALD include hepatic lipid accumulation. As the peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) has been shown to inhibit steatosis, the present study examined the role of PPARβ/δ in ALD coupling metabolomic, biochemical and molecular biological analyses. Wild-type and Pparβ/δ-null mice were fed either a control or 4% ethanol diet and examined after 4–7 months of treatment. Ethanol fed Pparβ/δ-null mice exhibited steatosis after short-term treatment compared to controls, the latter effect appeared to be due to increased activity of sterol regulatory element binding protein 1c (SREBP1c). The wild-type and Pparβ/δ-null mice fed the control diet showed clear differences in their urinary metabolomic profiles. In particular, metabolites associated with arginine and proline metabolism, and glycerolipid metabolism, were markedly different between genotypes suggesting a constitutive role for PPARβ/δ in the metabolism of these amino acids. Interestingly, urinary excretion of taurine was present in ethanol-fed wild-type mice but markedly lower in similarly treated Pparβ/δ-null mice. Evidence suggests that PPARβ/δ modulates pyridoxal kinase activity by altering K m , consistent with the observed decreased in urinary taurine excretion. These data collectively suggest that PPARβ/δ prevents ethanol-induced hepatic effects by inhibiting hepatic lipogenesis, modulation of amino acid metabolism, and altering pyridoxal kinase activity

Lithium-mediated protection against ethanol neurotoxicity

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Jia Luo

2010-06-01

Full Text Available Lithium has long been used as a mood stabilizer in the treatment of manic-depressive (bipolar disorder. Recent studies suggest that lithium has neuroprotective properties and may be useful in the treatment of acute brain injuries such as ischemia and chronic neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and amyotrophic lateral sclerosis. One of the most important neuroprotective properties of lithium is its anti-apoptotic action. Ethanol is a neuroteratogen and fetal alcohol spectrum disorders (FASD are caused by maternal ethanol exposure during pregnancy. FASD is the leading cause of mental retardation. Ethanol exposure causes neuroapoptosis in the developing brain. Ethanol-induced loss of neurons in the central nervous system underlies many of the behavioral deficits observed in FASD. Excessive alcohol consumption is also associated with Wernicke–Korsakoff syndrome and neurodegeneration in the adult brain. Recent in vivo and in vitro studies indicate that lithium is able to ameliorate ethanol-induced neuroapoptosis. Lithium is an inhibitor of glycogen synthase kinase 3 (GSK3 which has recently been identified as a mediator of ethanol neurotoxicity. Lithium’s neuroprotection may be mediated by its inhibition of GSK3. In addition, lithium also affects many other signaling proteins and pathways that regulate neuronal survival and differentiation. This review discusses the recent evidence of lithium-mediated protection against ethanol neurotoxicity and potential underlying mechanisms.

Synthesis, magnetic and ethanol gas sensing properties of semiconducting magnetite nanoparticles

Science.gov (United States)

Al-Ghamdi, Ahmed A.; Al-Hazmi, Faten; Al-Tuwirqi, R. M.; Alnowaiser, F.; Al-Hartomy, Omar A.; El-Tantawy, Farid; Yakuphanoglu, F.

2013-05-01

The superparamagnetic magnetite (Fe3O4) nanoparticles with an average size of 7 nm were synthesized using a rapid and facile microwave hydrothermal technique. The structure of the magnetite nanoparticles was characterized by X-ray diffraction (X-ray), field effect scanning electron microscopy (FESEM), energy dispersive X-ray spectroscopy (EDS), and transmission electron microscopy (TEM). The prepared Fe3O4 was shown to have a cubic phase of pure magnetite. Magnetization hysteresis loop shows that the synthesized magnetite exhibits no hysteretic features with a superparamagnetic behavior. The ethanol gas sensing properties of the synthesized magnetite were investigated, and it was found that the responsibility time is less than 10 s with good reproducibility for ethanol sensor. Accordingly, it is evaluated that the magnetite nanoparticles can be effectively used as a solid state ethanol sensor in industrial commercial product applications.

Ethanol fuels in Brazil

International Nuclear Information System (INIS)

Trindade, S.C.

1993-01-01

The largest alternative transportation fuels program in the world today is Brazil's Proalcool Program. About 6.0 million metric tons of oil equivalent (MTOE) of ethanol, derived mainly from sugar cane, were consumed as transportation fuels in 1991 (equivalent to 127,000 barrels of crude oil per day). Total primary energy consumed by the Brazilian economy in 1991 was 184.1 million MTOE, and approximately 4.3 million vehicles -- about one third of the total vehicle fleet or about 40 percent of the total car population -- run on hydrous or open-quotes neatclose quotes ethanol at the azeotropic composition (96 percent ethanol, 4 percent water, by volume). Additional transportation fuels available in the country are diesel and gasoline, the latter of which is defined by three grades. Gasoline A (regular, leaded gas)d has virtually been replaced by gasoline C, a blend of gasoline and up to 22 percent anhydrous ethanol by volume, and gasoline B (premium gasoline) has been discontinued as a result of neat ethanol market penetration

A crucial role for ethanol-induced oxidative stress in controlling lineage commitment of mesenchymal stromal cells through inhibition of wnt/beta-catenin signaling

Science.gov (United States)

Female skeletal responses to ethanol may vary depending on the physiologic status (viz. cycling, pregnancy, lactation). Nonetheless, ethanol-induced oxidative stress appears to be the key event leading to skeletal toxicity. In the current study, we chronically infused EtOH-containing liquid diets ...

Protective effects of aqueous and ethanolic extracts of Nigella sativa L. and Portulaca oleracea L. on free radical induced hemolysis of RBCs

Science.gov (United States)

Karimi, G; Aghasizadeh, M; Razavi, M; Taghiabadi, E

2011-01-01

Background and the purpose of the study It has been shown that Nigella sativa L. and Portulaca oleracea L. have many antioxidant components. In the present study, the cytoprotective effect of ethanolic and aqueous extracts of N.sativa and P.oleracea against hemolytic damages induced by free radical initiator, AAPH [2, 2’ azobis (2- amidinopropane) hydrochloride] was evaluated. Methods Hemolysis was induced by addition of AAPH. To study the cytoprotective effect, aqueous (50, 200, 300, 400, 800 µg/ml) and ethanolic (25, 100, 150, 200 and 400 µg/ml) extracts of N. sativa and aqueous (25, 50, 100, 150, 200 and 400 µg/ml) and ethanolic (300, 600, 900, 1200 and 1800 µg/ml) extracts of P. oleracea were employed. RBCs were incubated with both extracts and AAPH at 37 °C for 6 hrs. In order to evaluate the impact of the time of addition, extracts were added one and 2 hrs after AAPH. Samples of suspensions were removed at different times and the degree of hemolysis was assessed spectrophotometrically by reading the absorption of supernatants at 540 nm. Results Aqueous (300, 400 and 800 µg/ml) and ethanolic (150, 200 and 400 µg/ml) extracts of N.sativa and also, aqueous (100, 150, 200 and 400 µg/ml) and ethanolic (1200, 1800 µg/ml) extracts of P.oleracea showed concentration-dependent cytoprotective effects. Addition of extracts one hour after AAPH reduced but did not eliminate protective activities of extracts. Conclusion Cytorotective effect of aqueous and ethanolic extracts of N. sativa and P. oleracea against AAPH- induced hemolysis may be related to antioxidant properties of these plants. PMID:22615672

Desolvation of L-histidine and {alpha}-ketoisocaproic acid complex from ethanolate crystals under humidified conditions and influence of crystallinity on its desolvation; Histidine Ketoisocapron san ensan ethanol wamono kessho no koshitsudo jokenka deno datsu ethanol to datsu ethanol sei ni oyobosu kesshosei no eikyo

Energy Technology Data Exchange (ETDEWEB)

Kishimoto, S.; Tanabe, T.; Maruyama, S.; Kishishita, A.; Nagashima, N. [Ajinomoto Co. Inc., Tokyo (Japan)

1996-07-10

Desolvation of L-histidine and a-ketoisocaproic acid complex from ethanolate crystals was investigated. The ethanolate crystals were obtained from ethanol aqueous solutions of above 60 wt% of ethanol. It was difficult to remove ethanol molecules from the crystals lay vacuum drying. However, it was found that ethanol molecules in the crystal lattice could be released under humidified conditions, for example, 313 K and 60% relative humidity, accompanied by transformation to non-solvated crystals. When the peak of 2{theta}=9.0{degree}(CuK{alpha} radiation) in powder X-ray diffraction pattern of the ethanolate crystals was weak, ethanol molecules (about 1wt.%) remained in the crystals at the end of transformations and then the residual ethanol decreased slowly. A controlled moderate cooling process, where the supersaturation is released slowly, is the key point to obtain ethanolate crystals having high `crystallinity` (defined as peak height of 2{theta}=9.0{degree}) which shows quick desolation rather than adding ethanol for a rapid increase of supersaturation in crystallization. 6 refs., 7 figs.

INCREASES IN ANXIETY-LIKE BEHAVIOR INDUCED BY ACUTE STRESS ARE REVERSED BY ETHANOL IN ADOLESCENT BUT NOT ADULT RATS

OpenAIRE

Varlinskaya, Elena I.; Spear, Linda P.

2011-01-01

Repeated exposure to stressors has been found to increase anxiety-like behavior in laboratory rodents, with the social anxiety induced by repeated restraint being extremely sensitive to anxiolytic effects of ethanol in both adolescent and adult rats. No studies, however, have compared social anxiogenic effects of acute stress or the capacity of ethanol to reverse this anxiety in adolescent and adult animals. Therefore, the present study was designed to investigate whether adolescent [postnata...

Morphology-dependent activity of Pt nanocatalysts for ethanol oxidation in acidic media: Nanowires versus nanoparticles

International Nuclear Information System (INIS)

Zhou Weiping; Li Meng; Koenigsmann, Christopher; Ma Chao; Wong, Stanislaus S.; Adzic, Radoslav R.

2011-01-01

Highlights: → We demonstrate the morphology effect of Pt catalysts in electrooxidation of ethanol and CO in an acidic solution. → Pt nanowires and nanoparticles were used as catalysts. → Pt nanowires display a higher catalytic activity by a factor of at least two relative to those nanoparticles for ethanol oxidation. → The rate for CO monolayer oxidation exhibits similar morphology-dependent behavior with a markedly enhanced rate on the Pt nanowires. - Abstract: The morphology of nanostructured Pt catalysts is known to affect significantly the kinetics of various reactions. Herein, we report on a pronounced morphology effect in the electrooxidation of ethanol and carbon monoxide (CO) on Pt nanowires and nanoparticles in an acidic solution. The high resolution transmission electron microscopy analysis showed the inherent morphology difference between these two nanostructured catalysts. Voltammetric and chronoamperometric studies of the ethanol electrooxidation revealed that these nanowires had a higher catalytic activity by a factor of two relative to these nanoparticles. The rate for CO monolayer oxidation exhibits similar morphology-dependent behavior with a markedly enhanced rate on the Pt nanowires. In situ infrared reflection-absorption spectroscopy measurements revealed a different trend for chemisorbed CO formation and CO 2 -to-acetic acid reaction product ratios on these two nanostructures. The morphology-induced change in catalytic activity and selectivity in ethanol electrocatalysis is discussed in detail.

Morphology-dependent activity of Pt nanocatalysts for ethanol oxidation in acidic media: Nanowires versus nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Zhou Weiping, E-mail: wpzhou@bnl.gov [Chemistry Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Li Meng [Chemistry Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Koenigsmann, Christopher [Department of Chemistry, State University of New York at Stony Brook, Stony Brook, NY 11794 (United States); Ma Chao [Condensed Matter Physics and Materials Sciences Department, Brookhaven National Laboratory, Building 480, Upton, NY 11973 (United States); Wong, Stanislaus S. [Department of Chemistry, State University of New York at Stony Brook, Stony Brook, NY 11794 (United States); Condensed Matter Physics and Materials Sciences Department, Brookhaven National Laboratory, Building 480, Upton, NY 11973 (United States); Adzic, Radoslav R. [Chemistry Department, Brookhaven National Laboratory, Upton, NY 11973 (United States)

2011-11-30

Highlights: > We demonstrate the morphology effect of Pt catalysts in electrooxidation of ethanol and CO in an acidic solution. > Pt nanowires and nanoparticles were used as catalysts. > Pt nanowires display a higher catalytic activity by a factor of at least two relative to those nanoparticles for ethanol oxidation. > The rate for CO monolayer oxidation exhibits similar morphology-dependent behavior with a markedly enhanced rate on the Pt nanowires. - Abstract: The morphology of nanostructured Pt catalysts is known to affect significantly the kinetics of various reactions. Herein, we report on a pronounced morphology effect in the electrooxidation of ethanol and carbon monoxide (CO) on Pt nanowires and nanoparticles in an acidic solution. The high resolution transmission electron microscopy analysis showed the inherent morphology difference between these two nanostructured catalysts. Voltammetric and chronoamperometric studies of the ethanol electrooxidation revealed that these nanowires had a higher catalytic activity by a factor of two relative to these nanoparticles. The rate for CO monolayer oxidation exhibits similar morphology-dependent behavior with a markedly enhanced rate on the Pt nanowires. In situ infrared reflection-absorption spectroscopy measurements revealed a different trend for chemisorbed CO formation and CO{sub 2}-to-acetic acid reaction product ratios on these two nanostructures. The morphology-induced change in catalytic activity and selectivity in ethanol electrocatalysis is discussed in detail.

Methanolic extract of Morinda citrifolia L. (noni unripe fruit attenuates ethanol-induced conditioned place preferences in mice

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Yasmin Khan

2016-09-01

Full Text Available Phytotherapy is an emerging field successfully utilized to treat various chronic diseases including alcohol dependence. In the present study, we examined the effect of the standardized methanolic extract of Morinda citrifolia Linn. unripe fruit (MMC, on compulsive ethanol-seeking behaviour using the mouse conditioned place preference (CPP test. CPP was established by injections of ethanol (2g/kg, i.p. in a 12-day conditioning schedule in mice. The effect of MMC and the reference drug, acamprosate (ACAM, on the reinforcing properties of ethanol in mice was studied by the oral administration of MMC (1, 3 and 5g/kg and ACAM (300 mg/kg 60 min prior to the final CPP test postconditioning. Furthermore, CPPs weakened with repeated testing in the absence of ethanol over the next 12 days (extinction, during which the treatment groups received MMC (1, 3 and 5g/kg, p.o. or ACAM (300 mg/kg, p.o.. Finally, a priming injection of a low dose of ethanol (0.4g/kg, i.p. in the home cage (Reinstatement was sufficient to reinstate CPPs, an effect that was challenged by the administration of MMC or ACAM. MMC (3 and 5g/kg, p.o and ACAM (300 mg/kg, p.o. significantly reversed the establishment of ethanol-induced CPPs and effectively facilitated the extinction of ethanol CPP. In light of these findings, it has been suggested that M. citrifolia unripe fruit could be utilized for novel drug development to combat alcohol dependence.

Ethanol induces impulsive-like responding in a delay-of-reward operant choice procedure: impulsivity predicts autoshaping.

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Tomie, A; Aguado, A S; Pohorecky, L A; Benjamin, D

1998-10-01

Autoshaping conditioned responses (CRs) are reflexive and targeted motor responses expressed as a result of experience with reward. To evaluate the hypothesis that autoshaping may be a form of impulsive responding, within-subjects correlations between performance on autoshaping and impulsivity tasks were assessed in 15 Long-Evans hooded rats. Autoshaping procedures [insertion of retractable lever conditioned stimulus (CS) followed by the response-independent delivery of food (US)] were followed by testing for impulsive-like responding in a two-choice lever-press operant delay-of-reward procedure (immediate small food reward versus delayed large food reward). Delay-of-reward functions revealed two distinct subject populations. Subjects in the Sensitive group (n=7) were more impulsive-like, increasing immediate reward choices at longer delays for large reward, while those in the Insensitive group (n=8) responded predominantly on only one lever. During the prior autoshaping phase, the Sensitive group had performed more autoshaping CRs, and correlations revealed that impulsive subjects acquired the autoshaping CR in fewer trials. In the Sensitive group, acute injections of ethanol (0, 0.25, 0.50, 1.00, 1.50 g/kg) given immediately before delay-of-reward sessions yielded an inverted U-shaped dose-response curve with increased impulsivity induced by the 0.25, 0.50, and 1.00 g/kg doses of ethanol, while choice strategy of the Insensitive group was not influenced by ethanol dose. Ethanol induced impulsive-like responding only in rats that were flexible in their response strategy (Sensitive group), and this group also performed more autoshaping CRs. Data support the hypothesis that autoshaping and impulsivity are linked.

Effect of lawsonia innermis (linn) leaves ethanolic extract on blood glucose and malondialdehyde level in alloxan-induced diabetic rats

Science.gov (United States)

Indah Sari, Mutiara; Ilyas, Syafruddin; Widyawati, Tri; Anjelir Antika, Maya

2018-03-01

The case of diabetes mellitus (DM) tends to increase worldwide. DM triggers the oxidative stress condition that caused by the increasing of free radical. The present study was conducted to evaluate the effect of giving ethanolic extract of Lawsonia inermis (Linn) leaves to the glucose and malondialdehyde (MDA) level in alloxan-induced diabetic Wistar male rats. The powder of dry leaves of L.inermis was macerated in ethanol 96% to obtain ethanolic extract (LLEE).Thirty five of rats were divided into five groups, ie. K (normal and given 0.9% NaCl solution ), P1-P4 were induced using alloxan (120 mg/kg) intraperitoneally to get diabetic condition. Diabetic rats then were treated as follows: P1 (given 0.9% NaCl solution) P2 (LLEE (200 mg/kg BW), P3 (LLEE (400 mg/kg BW)), P4 ( LLEE (600 mg/kg BW)). All groups were treated for 28 days. The fasting blood glucose levels were measured at day 1, 7, 14, 21, 28 whereas MDA levels were measured at the end of treatment. The result showed that LLEE improved blood glucose level (BGLs) of alloxan-induced diabetic rats significantly (p 0.5). The study concluded that LLEE have antihyperglycemic properties.

Gastrointestinal protective effect of dietary spices during ethanol-induced oxidant stress in experimental rats.

Science.gov (United States)

Prakash, Usha N S; Srinivasan, Krishnapura

2010-04-01

Spices are traditionally known to have digestive stimulant action and to cure digestive disorders. In this study, the protective effect of dietary spices with respect to activities of antioxidant enzymes in gastric and intestinal mucosa was examined. Groups of Wistar rats were fed for 8 weeks with diets containing black pepper (0.5%), piperine (0.02%), red pepper (3.0%), capsaicin (0.01%), and ginger (0.05%). All these spices significantly enhanced the activities of antioxidant enzymes--superoxide dismutase, catalase, glutathione reductase, and glutathione-S-transferase--in both gastric and intestinal mucosa, suggesting a gastrointestinal protective role for these spices. In a separate study, these dietary spices were found to alleviate the diminished activities of antioxidant enzymes in gastric and intestinal mucosa under conditions of ethanol-induced oxidative stress. The gastroprotective effect of the spices was also reflected in their positive effect on mucosal glycoproteins, thereby lowering mucosal injury. The amelioration of the ethanol-induced decrease in the activities of antioxidant enzymes in gastric and intestinal mucosa by dietary spices suggests their beneficial gastrointestinal protective role. This is the first report on the gastrointestinal protective potential of dietary spices.

Renewable corn-ethanol and energy security

International Nuclear Information System (INIS)

Eaves, James

2007-01-01

Though corn-ethanol is promoted as renewable, models of the production process assume fossil fuel inputs. Moreover, ethanol is promoted as a means of increasing energy security, but there is little discussion of the dependability of its supply. This study investigates the sensibility of promoting corn-ethanol as an automobile fuel, assuming a fully renewable production process. We then use historical data to estimate the supply risk of ethanol relative to imported petroleum. We find that devoting 100% of US corn to ethanol would displace 3.5% of gasoline consumption and the annual supply of the ethanol would be inherently more risky than that of imported oil. Finally, because large temperature increases can simultaneously increase fuel demand and the cost of growing corn, the supply responses of ethanol producers to temperature-induced demand shocks would likely be weaker than those of gasoline producers. (author)

Loss of ethanol conditioned taste aversion and motor stimulation in knockin mice with ethanol-insensitive α2-containing GABA(A) receptors.

Science.gov (United States)

Blednov, Y A; Borghese, C M; McCracken, M L; Benavidez, J M; Geil, C R; Osterndorff-Kahanek, E; Werner, D F; Iyer, S; Swihart, A; Harrison, N L; Homanics, G E; Harris, R A

2011-01-01

GABA type A receptors (GABA(A)-Rs) are potential targets of ethanol. However, there are multiple subtypes of this receptor, and, thus far, individual subunits have not been definitively linked with specific ethanol behavioral actions. Interestingly, though, a chromosomal cluster of four GABA(A)-R subunit genes, including α2 (Gabra2), was associated with human alcoholism (Am J Hum Genet 74:705-714, 2004; Pharmacol Biochem Behav 90:95-104, 2008; J Psychiatr Res 42:184-191, 2008). The goal of our study was to determine the role of receptors containing this subunit in alcohol action. We designed an α2 subunit with serine 270 to histidine and leucine 277 to alanine mutations that was insensitive to potentiation by ethanol yet retained normal GABA sensitivity in a recombinant expression system. Knockin mice containing this mutant subunit were tested in a range of ethanol behavioral tests. These mutant mice did not develop the typical conditioned taste aversion in response to ethanol and showed complete loss of the motor stimulant effects of ethanol. Conversely, they also demonstrated changes in ethanol intake and preference in multiple tests. The knockin mice showed increased ethanol-induced hypnosis but no difference in anxiolytic effects or recovery from acute ethanol-induced motor incoordination. Overall, these studies demonstrate that the effects of ethanol at GABAergic synapses containing the α2 subunit are important for specific behavioral effects of ethanol that may be relevant to the genetic linkage of this subunit with human alcoholism.

Loss of Ethanol Conditioned Taste Aversion and Motor Stimulation in Knockin Mice with Ethanol-Insensitive α2-Containing GABAA Receptors

Science.gov (United States)

Borghese, C. M.; McCracken, M. L.; Benavidez, J. M.; Geil, C. R.; Osterndorff-Kahanek, E.; Werner, D. F.; Iyer, S.; Swihart, A.; Harrison, N. L.; Homanics, G. E.; Harris, R. A.

2011-01-01

GABA type A receptors (GABAA-Rs) are potential targets of ethanol. However, there are multiple subtypes of this receptor, and, thus far, individual subunits have not been definitively linked with specific ethanol behavioral actions. Interestingly, though, a chromosomal cluster of four GABAA-R subunit genes, including α2 (Gabra2), was associated with human alcoholism (Am J Hum Genet 74:705–714, 2004; Pharmacol Biochem Behav 90:95–104, 2008; J Psychiatr Res 42:184–191, 2008). The goal of our study was to determine the role of receptors containing this subunit in alcohol action. We designed an α2 subunit with serine 270 to histidine and leucine 277 to alanine mutations that was insensitive to potentiation by ethanol yet retained normal GABA sensitivity in a recombinant expression system. Knockin mice containing this mutant subunit were tested in a range of ethanol behavioral tests. These mutant mice did not develop the typical conditioned taste aversion in response to ethanol and showed complete loss of the motor stimulant effects of ethanol. Conversely, they also demonstrated changes in ethanol intake and preference in multiple tests. The knockin mice showed increased ethanol-induced hypnosis but no difference in anxiolytic effects or recovery from acute ethanol-induced motor incoordination. Overall, these studies demonstrate that the effects of ethanol at GABAergic synapses containing the α2 subunit are important for specific behavioral effects of ethanol that may be relevant to the genetic linkage of this subunit with human alcoholism. PMID:20876231

Hepatoprotective potential of ethanolic extract of Ziziphus oenoplia (L.) Mill roots against antitubercular drugs induced hepatotoxicity in experimental models.

Science.gov (United States)

Rao, Ch V; Rawat, A K S; Singh, Anil P; Singh, Arpita; Verma, Neeraj

2012-04-01

To evaluate the hepatoprotective potential of ethanolic (50%) extract of Ziziphus oenoplia (L.) Mill (Z. oenoplia) root against isoniazid (INH) and rifampicin (RIF) induced liver damage in animal models. Five groups of six rats each were selected for the study. Ethanolic extract at a dose of 150 and 300 mg/kg as well as silymarin (100 mg/kg) were administered orally once daily for 21 d in INH + RIF treated groups. The serum levels of glutamic oxaloacetic transaminase (SGOT), glutamate pyruvate transaminase (SGPT), alkaline phosphatase (SALP), and bilirubin were estimated along with activities of superoxide dismutase, catalase, glutathione S-transferase, glutathione peroxidase, and hepatic melondialdehyde formation. Histopathological analysis was carried out to assess injury to the liver. The considerably elevated serum enzymatic activities of glutamic oxaloacetic transaminase, glutamate pyruvate transaminase, alkaline phosphatase and bilirubin due to INH + RIF treatment were restored towards normal in a dose dependent manner after the treatment with ethanolic extract of Z. oenoplia roots. Meanwhile, the decreased activities of superoxide dismutase, catalase, glutathione S-transferase and glutathione peroxidase were also restored towards normal dose dependently. In addition, ethanolic extract also significantly prevented the elevation of hepatic melondialdehyde formation in the liver of INH + RIF intoxicated rats in a dose dependent manner. The biochemical observations were supplemented with histopathological examination of rat liver sections. The results of this study strongly indicate that ethanolic extract of Z. oenoplia has a potent hepatoprotective action against INH + RIF induced hepatic damage in rats. Copyright © 2012 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Pathophysiology of chronic pancreatitis induced by dibutyltin dichloride joint ethanol in mice.

Science.gov (United States)

Zhang, Hong; Liu, Bin; Xu, Xiao-Fan; Jiang, Ting-Ting; Zhang, Xiao-Qin; Shi, Ying-Li; Chen, Yu; Liu, Fang; Gu, Jie; Zhu, Lin-Jia; Wu, Nan

2016-03-14

To search for a new chronic pancreatitis model in mice suitable for investigating the pathophysiological processes leading to pancreatic fibrosis. The mice were randomly divided into 2 groups (n = 50), control group and model group. The mice in model group were given ethanol (10%) in drinking water after injection of dibutyltin dichloride (DBTC) (8 mg/kg BW) in tail vein. The mice in control group were injected with only solvent into tail vein (60% ethanol, 20% glycerine and 20% normal saline) and drank common water. At days 1, 7, 14, 28, and 56 after application of DBTC or solvent, 10 mice in one group were killed at each time point respectively. Blood was obtained by inferior vena cava puncture. The activity of amylase, concentration of bilirubin and hyaluronic acid in serum were assayed. The pancreas was taken to observe the pancreatic morphology by HE staining, and to characterize the pancreatic fibrosis by Masson staining. The expression of F4/80, CD3 and fibronectin (FN) were assayed by immuno-histochemistry or Immunofluorescence technique. Collagen type I (COL1A1) in pancreas were detected by Western blot. The expression of matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinases-1 (TIMP-1) mRNA in the pancreas was assessed by real time PCR. DBTC induced an acute edematous pancreatitis within 1 d. The dilated acini, scattered acinar cell necrosis, and inflammatory cells were found at day 7. Extensive infiltration with inflammatory cells following deposition of connective tissue was observed at day 14. At day 28, level of pancreatic fibrosis was aggravated. The pancreatic tissue was replaced by an extended interstitial fibrosis at the end of 2 mo. There was significant difference in the level of amylase, bilirubin and hyaluronic acid in serum between control group and model group (P chronic pancreatitis in accordance with the pathophysiological modification of human. DBTC joint Ethanol-induced pancreatitis in mice is an effective and

The neuroprotective effects of an ethanolic turmeric (Curcuma longa L.) extract against trimethyltin-induced oxidative stress in rats.

Science.gov (United States)

Yuliani, Sapto; Mustofa; Partadiredja, Ginus

2018-03-07

Oxidative stress is known to contribute to the pathogenesis of neurodegenerative disorders. An ethanolic turmeric (Curcuma longa L.) extract containing curcumin has been reported to produce antioxidant effects. The present study aims to investigate the possible neuroprotective effects of the ethanolic turmeric extract against trimethyltin (TMT)-induced oxidative stress in Sprague Dawley rats. The ethanolic turmeric extract and citicoline were administered to the TMT exposed rats from day 1 to day 28 of the experiment. The TMT injection was administered on day 8 of the experiment. The plasma and brain malondialdehyde (MDA) and reduced glutathione (GSH) levels, and the activities of the superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) enzymes in the brain were examined at the end of the experiment. The administration of 200 mg/kg bw of the ethanolic turmeric extract prevented oxidative stress by decreasing the plasma and brain MDA levels and increasing the SOD, CAT, and GPx enzyme activities and GSH levels in the brain. These effects seem to be comparable to those of citicoline. The ethanolic turmeric extract at a dose of 200 mg/kg bw may exert neuroprotective effects on TMT-exposed Sprague Dawley rats by preventing them from oxidative stress.

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

OpenAIRE

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)...

Ethanol vapour induced dilated cardiomyopathy in chick embryos

International Nuclear Information System (INIS)

Kamran, K.; Khan, M.Y.; Minhas, L.A.

2013-01-01

Objective: To study the effects of ethanol vapour inhalation on the heart chambers of chick embryo. Methods: The case-control study was conducted at the College of Physicians and Surgeons Pakistan regional centre in Islamabad from January to October 2007. Both experimental and control groups were divided into three sub-groups each, based on the day of the sacrifice. Each group was dissected on day 7, day 10 and day 22 or hatching whichever was earlier. The experimental sub-groups sacrificed on day 7, day 10 and on hatching, were exposed to ethanol vapours till day 6, 9 and 9 of incubation respectively. The diameter of all 4 chambers was measured in experimental hearts and compared with age-matched controls. SPSS 10 was used for statistical analysis. Results: Ethanol vapour exposure caused widening of all heart chambers in the experimental chick embryos sacrificed on day 7 and day 10 compared to the controls. The chambers of newly hatched chick hearts showed dilatation in all the chambers except the left ventricle. Conclusion: Ethanol vapour exposure during development affects the heart, resulting in the widening of all heart chambers. The exposure is as dangerous as drinking alcohol. Alcohol vapour exposure during development leads to progressive dilatation in different heart chambers, producing dilated cardiomyopathy. (author)

Protective effects of aqueous and ethanolic extracts of Nigella sativa L.and Portulaca oleracea L. on free radical induced hemolysis of RBCs

Directory of Open Access Journals (Sweden)

E Taghiabadi

2011-10-01

Full Text Available "n  Background and the purpose of the study: It has been shown that Nigella sativa L. and Portulaca oleracea L. have many antioxidant components. In the present study, the cytoprotective effect of ethanolic and aqueous extracts of N.sativa and P.oleracea against hemolytic damages induced by free radical initiator, AAPH [2, 2' azobis (2- amidinopropane hydrochloride] was evaluated. "n  Methods: Hemolysis was induced by addition of AAPH. To study the cytoprotective effect, aqueous (50, 200, 300, 400, 800 μg/ml and ethanolic (25, 100, 150, 200 and 400 μg/ml extracts of N. sativa and aqueous (25, 50, 100, 150, 200 and 400 μg/ml and ethanolic (300, 600, 900, 1200 and 1800 μg/ml extracts of P. oleracea were employed. RBCs were incubated with both extracts and AAPH at 37 °C for 6 hrs. In order to evaluate the impact of the time of addition, extracts were added one and 2 hrs after AAPH. Samples of suspensions were removed at different times and the degree of hemolysis was assessed spectrophotometrically by reading the absorption of supernatants at 540 nm. "n  Results: Aqueous (300, 400 and 800 μg/ml and ethanolic (150, 200 and 400 μg/ml extracts of N.sativa and also, aqueous (100, 150, 200 and 400 μg/ml and ethanolic (1200, 1800 μg/ml extracts of P.oleracea showed concentration-dependent cytoprotective effects. Addition of extracts one hour after AAPH reduced but did not eliminate protective activities of extracts. "n  Conclusion: Cytorotective effect of aqueous and ethanolic extracts of N. sativa and P. oleracea against AAPH- induced hemolysis may be related to antioxidant properties of these plants.

influence of fructose on the mechanisms for ethanol- induced ...

African Journals Online (AJOL)

Mgina

TAG production. Table 1, shows that ethanol + fructose consumption increased plasma VLDL- and. HDL- but decreased LDL- components. These data suggest that in the presence of fructose, ethanol may produce accelerated clearance of LDL, decreased conversion of. VLDL to LDL or increased hepatic synthesis of VLDL.

Antidiabetic Activity Test of Ethanolic Seri Leave’s (Muntingia Calabura L. Extract in Male Rats Induced by Alloxan

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Herlina Herlina

2018-01-01

Full Text Available Antidiabetic activity test of ethanol extract of seri leave (Muntingia calabura L. rats induced by alloxan has been done. Male wistar albino rats are used as animal models which divided into 6 groups, normal group (aquadest, negative control group (Na CMC 0,5%, positive control group (glibenclamide 0,43 mg/200 gBB, and 1, 2, and 3 treatment groups (ethanol extract of seri leave 65, 130, dan 260 mg/kgBB. Rats blood glucose level after induced intraperitoneally by alloxan 130 mg/kgBB can be stated as diabetes when >200 mg/dL. Preprandial blood glucose levels are measured using DTN-410-K photometer, on day 0, 5, 10, and 15. The average result of AUC0-15 and percentage of decreasing blood glucose level for positive control group are 2732,5 and 37,43%, and 3 treatment groups (65 mg/kgBB, 130 mg/kgBB, and 260 mg/kgBB 3105 and 28,90%; 2962,5 and 32,16%; 2810 and 35,66%. This point indicated that the ethanol extract of seri leave has an antidiabetic activity and there is no significant difference compared with glibenclamide (p<0,05. Percentage of blood glucose decrease level the third treatment group there is no significant difference compare with positive control group. According to the relation between percentage of blood glucose decrease level with dose, value of ED50 of ethanol extract of seri leave is 692,424 mg/kgBB.

Role of cannabinoidergic mechanisms in ethanol self-administration and ethanol seeking in rat adult offspring following perinatal exposure to Δ9-tetrahydrocannabinol

International Nuclear Information System (INIS)

Economidou, Daina; Mattioli, Laura; Ubaldi, Massimo; Lourdusamy, Anbarasu; Soverchia, Laura; Hardiman, Gary; Campolongo, Patrizia; Cuomo, Vincenzo; Ciccocioppo, Roberto

2007-01-01

The present study evaluated the consequences of perinatal Δ 9 -tetrahydrocannabinol (Δ 9 -THC) treatment (5 mg/kg/day by gavage), either alone or combined with ethanol (3% v/v as the only fluid available), on ethanol self-administration and alcohol-seeking behavior in rat adult offspring. Furthermore, the effect of the selective cannabinoid CB 1 receptor antagonist, SR-141716A, on ethanol self-administration and on reinstatement of ethanol-seeking behavior induced either by stress or conditioned drug-paired cues was evaluated in adult offspring of rats exposed to the same perinatal treatment. Lastly, microarray experiments were conducted to evaluate if perinatal treatment with Δ 9 -tetrahydrocannabinol, ethanol or their combination causes long-term changes in brain gene expression profile in rats. The results of microarray data analysis showed that 139, 112 and 170 genes were differentially expressed in the EtOH, Δ 9 -THC, or EtOH + Δ 9 -THC group, respectively. No differences in alcohol self-administration and alcohol seeking were observed between rat groups. Intraperitoneal (IP) administration of SR-141716A (0.3-3.0 mg/kg) significantly reduced lever pressing for ethanol and blocked conditioned reinstatement of alcohol seeking. At the same doses SR-141716A failed to block foot-shock stress-induced reinstatement of alcohol seeking. The results reveal that perinatal exposure to Δ 9 -THC ethanol or their combination results in evident changes in gene expression patterns. However, these treatments do not significantly affect vulnerability to ethanol abuse in adult offspring. On the other hand, the results obtained with SR-141716A emphasize that endocannabinoid mechanisms play a major role in ethanol self-administration, as well as in the reinstatement of ethanol-seeking behavior induced by conditioned cues, supporting the idea that cannabinoid CB 1 receptor antagonists may represent interesting agents for the pharmacotherapy of alcoholism

Experimental investigation and modeling of adsorption of water and ethanol on cornmeal in an ethanol-water binary vapor system

Energy Technology Data Exchange (ETDEWEB)

Chang, H.; Yuan, X.G.; Tian, H.; Zeng, A.W. [State Key Laboratory of Chemical Engineering, Tianjin University, Tianjin 300072 (China)

2006-04-15

The adsorption capacity of water and ethanol on cornmeal in an ethanol-water binary vapor system was investigated in a fixed-bed apparatus for ethanol dehydration. Experiments were performed at temperatures of 82-100 C for different relative humidities of ethanol-water vapor. Adsorption equilibrium models, including those based on the adsorption potential theory of Polanyi and Sircar's model, have been used to fit the experimental data for water adsorption on cornmeal, and all gave good fits. For ethanol adsorption, pseudo-equilibrium was defined as the mass adsorbed on the cornmeal within the time needed for the equilibrium for water on the same adsorbent. Based on this limiting condition, adsorption behaviors and mechanisms were analyzed. (Abstract Copyright [2006], Wiley Periodicals, Inc.)

Veronicastrum axillare Alleviates Ethanol-Induced Injury on Gastric Epithelial Cells via Downregulation of the NF-kB Signaling Pathway

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Wei-chun Zhao

2017-01-01

Full Text Available We used human gastric epithelial cells (GES-1 line in an ethanol-induced cell damage model to study the protective effect of Veronicastrum axillare and its modulation to NF-κB signal pathway. The goal was to probe the molecular mechanism of V. axillare decoction in the prevention of gastric ulcer and therefore provide guidance in the clinical application of V. axillare on treating injuries from chronic nephritis, pleural effusion, gastric ulcer, and other ailments. The effects of V. axillare-loaded serums on cell viability were detected by MTT assays. Enzyme-linked immunosorbent assay (ELISA and Real-Time PCR methods were used to analyze the protein and mRNA expression of TNF-α, NF-κB, IκBα, and IKKβ. The results showed that V. axillare-loaded serum partially reversed the damaging effects of ethanol and NF-κB activator (phorbol-12-myristate-13-acetate: PMA and increased cell viability. The protein and mRNA expressions of TNF-α, NF-κB, IκBα, and IKKβ were significantly upregulated by ethanol and PMA while they were downregulated by V. axillare-loaded serum. In summary, V. axillare-loaded serum has significantly protective effect on GES-1 against ethanol-induced injury. The protective effect was likely linked to downregulation of TNF-α based NF-κB signal pathway.

26 CFR 48.4041-19 - Exemption for qualified methanol and ethanol fuel.

Science.gov (United States)

2010-04-01

... 26 Internal Revenue 16 2010-04-01 2010-04-01 true Exemption for qualified methanol and ethanol....4041-19 Exemption for qualified methanol and ethanol fuel. (a) In general. Under section 4041(b)(2... or use of qualified methanol or ethanol fuel. (b) Qualified methanol or ethanol fuel defined. For...

Antioxidant Mechanism is Involved in the Gastroprotective Effects of Ozonized Sunflower Oil in Ethanol-Induced Ulcers in Rats

Directory of Open Access Journals (Sweden)

Zullyt B. Zamora Rodríguez

2007-01-01

In summary, our results demonstrate that OSO pretreatment exerts protective effects in ethanol-induced gastric ulcers in rats. Furthermore, these results provide evidence that these protective effects of OSO are mediated at least partially by stimulation of some important antioxidant enzymes such as SOD and GSH-Px, which are scavengers of ROS and therefore prevent gastric injury induced by them.

Prenatal ethanol exposure-induced adrenal developmental abnormality of male offspring rats and its possible intrauterine programming mechanisms

Energy Technology Data Exchange (ETDEWEB)

Huang, Hegui; He, Zheng; Zhu, Chunyan; Liu, Lian; Kou, Hao; Shen, Lang [Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan 430071 (China); Wang, Hui, E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan 430071 (China); Hubei Provincial Key Laboratory of Developmentally Originated Disorder, Wuhan 430071 (China)

2015-10-01

Fetal adrenal developmental status is the major determinant of fetal tissue maturation and offspring growth. We have previously proposed that prenatal ethanol exposure (PEE) suppresses fetal adrenal corticosterone (CORT) synthesis. Here, we focused on PEE-induced adrenal developmental abnormalities of male offspring rats before and after birth, and aimed to explore its intrauterine programming mechanisms. A rat model of intrauterine growth retardation (IUGR) was established by PEE (4 g/kg·d). In PEE fetus, increased serum CORT concentration and decreased insulin-like growth factor 1 (IGF1) concentration, with lower bodyweight and structural abnormalities as well as a decreased Ki67 expression (proliferative marker), were observed in the male fetal adrenal cortex. Adrenal glucocorticoid (GC)-metabolic activation system was enhanced while gene expression of IGF1 signaling pathway with steroidogenic acute regulatory protein (StAR), 3β-hydroxysteroid dehydrogenase (3β-HSD) was decreased. Furthermore, in the male adult offspring of PEE, serum CORT level was decreased but IGF1 was increased with partial catch-up growth, and Ki67 expression demonstrated no obvious change. Adrenal GC-metabolic activation system was inhibited, while IGF1 signaling pathway and 3β-HSD was enhanced with the steroidogenic factor 1 (SF1), and StAR was down-regulated in the adult adrenal. Based on these findings, we propose a “two-programming” mechanism for PEE-induced adrenal developmental toxicity: “the first programming” is a lower functional programming of adrenal steroidogenesis, and “the second programming” is GC-metabolic activation system-related GC-IGF1 axis programming. - Highlights: • Prenatal ethanol exposure induces adrenal developmental abnormality in offspring rats. • Prenatal ethanol exposure induces intrauterine programming of adrenal steroidogenesis. • Intrauterine GC-IGF1 axis programming might mediate adrenal developmental abnormality.

Prenatal ethanol exposure-induced adrenal developmental abnormality of male offspring rats and its possible intrauterine programming mechanisms

International Nuclear Information System (INIS)

Huang, Hegui; He, Zheng; Zhu, Chunyan; Liu, Lian; Kou, Hao; Shen, Lang; Wang, Hui

2015-01-01

Fetal adrenal developmental status is the major determinant of fetal tissue maturation and offspring growth. We have previously proposed that prenatal ethanol exposure (PEE) suppresses fetal adrenal corticosterone (CORT) synthesis. Here, we focused on PEE-induced adrenal developmental abnormalities of male offspring rats before and after birth, and aimed to explore its intrauterine programming mechanisms. A rat model of intrauterine growth retardation (IUGR) was established by PEE (4 g/kg·d). In PEE fetus, increased serum CORT concentration and decreased insulin-like growth factor 1 (IGF1) concentration, with lower bodyweight and structural abnormalities as well as a decreased Ki67 expression (proliferative marker), were observed in the male fetal adrenal cortex. Adrenal glucocorticoid (GC)-metabolic activation system was enhanced while gene expression of IGF1 signaling pathway with steroidogenic acute regulatory protein (StAR), 3β-hydroxysteroid dehydrogenase (3β-HSD) was decreased. Furthermore, in the male adult offspring of PEE, serum CORT level was decreased but IGF1 was increased with partial catch-up growth, and Ki67 expression demonstrated no obvious change. Adrenal GC-metabolic activation system was inhibited, while IGF1 signaling pathway and 3β-HSD was enhanced with the steroidogenic factor 1 (SF1), and StAR was down-regulated in the adult adrenal. Based on these findings, we propose a “two-programming” mechanism for PEE-induced adrenal developmental toxicity: “the first programming” is a lower functional programming of adrenal steroidogenesis, and “the second programming” is GC-metabolic activation system-related GC-IGF1 axis programming. - Highlights: • Prenatal ethanol exposure induces adrenal developmental abnormality in offspring rats. • Prenatal ethanol exposure induces intrauterine programming of adrenal steroidogenesis. • Intrauterine GC-IGF1 axis programming might mediate adrenal developmental abnormality.

IMMUNOHISTOCHEMICAL APPROACH REVEALS LOCALIZATION OF CYSTATHIONINE-?-LYASE AND CYSTATHIONINE-ß-SYNTHETASE IN ETHANOL-INDUCED GASTRIC MUCOSA DAMAGE IN MICE

Directory of Open Access Journals (Sweden)

Jand-Venes Rolim MEDEIROS

2013-04-01

Full Text Available Context Hydrogen sulphide (H2S has been proved to be a neuromodulator and contributes to the maintenance of gastric mucosal integrity in damage caused by anti-inflammatory nonsteroidal drugs. Previously, we demonstrated that H2S synthesis is essential to gastric protection against ethanol. Objective To better understanding the role of H2S and the detailed localization of its production in both normal and injured stomach due to ethanol injection, we studied the expression of cystathionine-γ-lyase (CSE and cystathionine-β-synthetase (CBS isoforms in gastric mucosa of mice treated with saline or 50% ethanol. Methods Mice were treated by gavage with saline or 50% ethanol (0.5 mL/25 g. After 1 hour, mice were sacrificed, and gastric tissue was evaluated by histological and immunohistochemical analysis specific for CSE and CBS. Results We have demonstrated a non-specific expression of CBS in the normal gastric mucosa and expression of CSE occurring mainly in the parietal cells of the animals treated with ethanol. Conclusion Thus, we demonstrated that the expression of CBS appears to be constitutive and diffuse across the gastric epithelium, while the expression of CSE appears to be induced in parietal cells by damage agents such as ethanol.

Effects of topiramate and other anti-glutamatergic drugs on the acute intoxicating actions of ethanol in mice: modulation by genetic strain and stress

Science.gov (United States)

Chen, Yi-Chyan; Holmes, Andrew

2008-01-01

Compounds with anti-glutamatergic properties currently in clinical use for various indications (e.g., Alzheimer's disease, epilepsy, psychosis, mood disorders) have potential utility as novel treatments for alcoholism. Enhanced sensitivity to certain acute intoxicating effects (ataxia, sedative) of alcohol may be one mechanism by which anti-glutamatergic drugs modulate alcohol use. We examined the effects of six compounds (memantine, dextromethorphan, haloperidol, lamotrigine, oxcarbazepine, topiramate) on sensitivity to acute intoxicating effects of ethanol (ataxia, hypothermia, sedation/hypnosis) in C57BL/6J mice. Analysis of topiramate was extended to determine the influence of genetic background (via comparison of the 129S1, BALB/cJ, C57BL/6J, DBA/2J inbred strains) and prior stress history (via chronic exposure of C57BL/6J to swim stress) on topiramate's effects on ethanol-induced sedation/hypnosis. Results showed that one N-methyl-D-aspartate receptor (NMDAR) antagonist, memantine, but not another, dextromethorphan, potentiated the ataxic but not hypothermic or sedative/hypnotic effects of ethanol. Haloperidol increased ethanol-induced ataxia and sedation/hypnosis to a similar extent as the prototypical NMDAR antagonist MK-801. Of the anticonvulsants tested, lamotrigine accentuated ethanol-induced sedation/hypnosis, while oxcarbazepine was without effect. Topiramate was without effect per se under baseline conditions in C57BL/6J, but had a synergistic effect with MK-801 on ethanol-induced sedation/hypnosis. Comparing inbred strains, topiramate was found to significantly potentiated ethanol's sedative/hypnotic effects in BALB/cJ, but not 129S1, C57BL/6J or DBA/2J strains. Topiramate also increased ethanol-induced sedation/hypnosis in C57BL/6J after exposure to chronic stress exposure. Current data demonstrate that, with the exception of MK-801 and haloperidol, the compounds tested had either no significant or assay-selective effects on sensitivity to acute

Chronic Ethanol Consumption in Mice Alters Hepatocyte Lipid Droplet Properties

Science.gov (United States)

Orlicky, David J.; Roede, James R.; Bales, Elise; Greenwood, Carrie; Greenberg, Andrew; Petersen, Dennis; McManaman, James L.

2014-01-01

Background Hepatosteatosis is a common pathological feature of impaired hepatic metabolism following chronic alcohol consumption. Although often benign and reversible, it is widely believed that steatosis is a risk factor for development of advanced liver pathologies, including steatohepatitis and fibrosis. The hepatocyte alterations accompanying the initiation of steatosis are not yet clearly defined. Methods Induction of hepatosteatosis by chronic ethanol consumption was investigated using the Lieber-DeCarli (LD) high fat diet model. Effects were assessed by immunohistochemistry and blood and tissue enzymatic assays. Cell culture models were employed for mechanistic studies. Results Pair feeding mice ethanol (LD-Et) or isocaloric control (LD-Co) diets for 6 weeks progressively increased hepatocyte triglyceride accumulation in morphological, biochemical, and zonally distinct cytoplasmic lipid droplets (CLD). The LD-Et diet induced zone 2-specific triglyceride accumulation in large CLD coated with perilipin, adipophilin (ADPH), and TIP47. In LD-Co- fed mice, CLD were significantly smaller than those in LD-Et-fed mice and lacked perilipin. A direct role of perilipin in formation of large CLD was further suggested by cell culture studies showing that perilipin-coated CLD were significantly larger than those coated with ADPH or TIP47. LD-Co- and LD-Et-fed animals also differed in hepatic metabolic stress responses. In LD-Et but not LD-Co-fed mice, inductions were observed in the following: microsomal ethanol-oxidizing system [cytochrome P-4502E1 (CYP2E1)], hypoxia response pathway (hypoxia-inducible factor 1 alpha, HIF1α), endoplasmic reticulum stress pathway (calreticulin), and synthesis of lipid peroxidation products [4-hydroxynonenal (4-HNE)]. CYP2E1 and HIF1 α immunostaining localized to zone 3 and did not correlate with accumulation of large CLD. In contrast, calreticulin and 4-HNE immunostaining closely correlated with large CLD accumulation. Importantly, 4

Identification and ultrastructural imaging of photodynamic therapy-induced microfilaments by atomic force microscopy

International Nuclear Information System (INIS)

Jung, Se-Hui; Park, Jin-Young; Yoo, Je-Ok; Shin, Incheol; Kim, Young-Myeong; Ha, Kwon-Soo

2009-01-01

Atomic force microscopy (AFM) is an emerging technique for imaging biological samples at subnanometer resolution; however, the method is not widely used for cell imaging because it is limited to analysis of surface topology. In this study, we demonstrate identification and ultrastructural imaging of microfilaments using new approaches based on AFM. Photodynamic therapy (PDT) with a new chlorin-based photosensitizer DH-II-24 induced cell shrinkage, membrane blebbing, and reorganization of cytoskeletons in bladder cancer J82 cells. We investigated cytoskeletal changes using confocal microscopy and atomic force microscopy. Extracellular filaments formed by PDT were analyzed with a tandem imaging approach based on confocal microscopy and atomic force microscopy. Ultrathin filaments that were not visible by confocal microscopy were identified as microfilaments by on-stage labeling/imaging using atomic force microscopy. Furthermore, ultrastructural imaging revealed that these microfilaments had a stranded helical structure. Thus, these new approaches were useful for ultrastructural imaging of microfilaments at the molecular level, and, moreover, they may help to overcome the current limitations of fluorescence-based microscopy and atomic force microscopy in cell imaging.

Ethanol Forensic Toxicology.

Science.gov (United States)

Perry, Paul J; Doroudgar, Shadi; Van Dyke, Priscilla

2017-12-01

Ethanol abuse can lead to negative consequences that oftentimes result in criminal charges and civil lawsuits. When an individual is suspected of driving under the influence, law enforcement agents can determine the extent of intoxication by measuring the blood alcohol concentration (BAC) and performing a standardized field sobriety test. The BAC is dependent on rates of absorption, distribution, and elimination, which are influenced mostly by the dose of ethanol ingested and rate of consumption. Other factors contributing to BAC are gender, body mass and composition, food effects, type of alcohol, and chronic alcohol exposure. Because of individual variability in ethanol pharmacology and toxicology, careful extrapolation and interpretation of the BAC is needed, to justify an arrest and assignment of criminal liability. This review provides a summary of the pharmacokinetic properties of ethanol and the clinical effects of acute intoxication as they relate to common forensic questions. Concerns regarding the extrapolation of BAC and the implications of impaired memory caused by alcohol-induced blackouts are discussed. © 2017 American Academy of Psychiatry and the Law.

Autoshaping of ethanol drinking: an animal model of binge drinking.

Science.gov (United States)

Tomie, Arthur; di Poce, Jason; Derenzo, Christopher C; Pohorecky, Larissa A

2002-01-01

To examine the hypothesis that Pavlovian autoshaping provides an animal learning model of drug abuse, two studies evaluated the induction of ethanol drinking by autoshaping procedures. In Experiment 1, the sipper tube conditioned stimulus (CS) contained saccharin/ethanol solution and was repeatedly paired with food as an unconditioned stimulus (US). The CS-US paired group consumed more of the 0.1% saccharin-6% ethanol solution than did the CS-US random group, revealing that autoshaping conditioned responses (CR) induce ethanol drinking not attributable to pseudo-conditioning. Experiment 2 employed saccharin-fading procedures and showed that the paired vs random group differences in ethanol drinking were maintained, even as the saccharin was eliminated from the solution. The results show that Pavlovian autoshaping procedures induce high volumes of ethanol drinking when the presentation of a sipper tube containing an ethanol solution precedes the response-independent delivery of food. The high volume of ethanol consumed in a brief period of time suggests that Pavlovian autoshaping may be a model of binge drinking.

Control of Biofilm Formation in Fungi Using Ethanol

International Nuclear Information System (INIS)

El Sebaey, R.T.

2015-01-01

The use of fungi in biotechnology requires that no cell loss takes place; a maximal level of cell-nutrient interaction is required to achieve efficient performance and avoid cell loss. The main aim of the present study is to use ethanol to control cell-cell and cell-surface adhesion through manipulating cell surface properties. A Fungal isolate with a phenol oxidase activity (43.2 U/ml) was chosen out of twelve isolates belonging to two main genera: Aspergillus sp. and Penicillium sp. The fungus isolate, assigned as the highest phenol oxidase producer, was morphologically identified as Penicillium purpurogenum. Penicillium purpurogenum formed a ring around the bottle in static and shaking conditions, therefore, a number of different stress conditions, such as ph, temperature, different nitrogen sources, gamma radiation and ethanol, were employed separately to control biofilm formation in the fungus under study. The fungus was tested for its morphology, mycelia weight, stress response (catalase, lipid peroxidation and red pigment synthesis) and extracellular and surface bound protein and exo polysaccharides. The obtained results correlate the biofilm formation to stress response and surface bound protein. Combining all types of stress did not result in more biofilm formation control; on the contrary, it posed more stress on the fungus and affected the biomass. Ethanol on its own was successively used to control biofilm, which was inhibited in the presence of 2.5% v/v ethanol without affecting the growth. The addition of ethanol also increased the intracellular phenol oxidase activity from 43.2 to 228.43 U/ml. scanning electron microscopy showed that the addition of ethanol resulted in the formation of loose mycelia network as compared to a tight mycelia network in ethanol free cultures. The presence of Yap1p gene, the detection of an oxidized form of glutathione (GSSG) and catalase after ethanol addition all suggest that a stress response might be involved in the

Ethanol acts as a potent agent sensitizing colon cancer cells to the TRAIL-induced apoptosis

Czech Academy of Sciences Publication Activity Database

Vaculová, Alena; Hofmanová, Jiřina; Souček, Karel; Anděra, Ladislav; Kozubík, Alois

2004-01-01

Roč. 577, 1-2 (2004), s. 309-313 ISSN 0014-5793 R&D Projects: GA ČR GA524/04/0895; GA AV ČR KSK5011112; GA AV ČR IBS5004009 Institutional research plan: CEZ:AV0Z5004920 Keywords : TNF-related apoptosis-inducing ligand * ethanol * apoptosis Subject RIV: BO - Biophysics Impact factor: 3.843, year: 2004

Explaining the reductions in US corn ethanol processing costs: Testing competing hypotheses

International Nuclear Information System (INIS)

Chen Xiaoguang; Khanna, Madhu

2012-01-01

The processing costs of US corn ethanol have declined by 45% since 1983 as production volumes have increased seventeen-fold. We investigate the role of various factors that could explain this, including economies of scale, cumulative experience, induced innovation in response to rising input prices, an autonomous technological change, and trade induced competition from imported ethanol. Using data on dry-mill ethanol processing costs over the 1983–2005 period, we find evidence to show that US corn ethanol production exhibited decreasing returns to scale, that learning by doing played an important role in reducing these processing costs with a learning rate of 0.25, and that sugarcane ethanol imports contributed to making the corn ethanol industry more competitive. Other factors such as the rising prices of energy and labor did induce lower processing costs, but the effect is not statistically significant. The inclusion of these competing explanations for the reduction in processing costs of US corn ethanol lead to a significantly higher learning rate than otherwise, and this learning rate is found to be robust across specifications. - Highlights: ► We investigate the role of various factors that could explain the reduction in US corn ethanol processing costs over the period 1983–2005. ► We find that US corn ethanol production exhibited decreasing returns to scale. ► Learning by doing played an important role in reducing these costs with a learning rate of 0.25. ► Sugarcane ethanol imports contributed to making the corn ethanol industry more competitive. ► Rising prices of energy and labor did induce lower processing costs, but the effect is not statistically significant.

Palladium-based electrocatalysts for ethanol oxidation reaction in alkaline direct ethanol fuel cell

Energy Technology Data Exchange (ETDEWEB)

Moraes, Leticia Poras Reis de; Amico, Sandro Campos; Malfatti, Celia de Fraga, E-mail: leticiamoraes@usp.br [Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre (Brazil); Matos, Bruno R.; Santiago, Elisabete Inacio; Fonseca, Fabio Coral [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

2016-07-01

Full text: Direct ethanol fuel cells require adequate electrocatalysts to promote the carbon carbon cleavage of ethanol molecule. Typical electrocatalysts are based on platinum, which have shown improved activity in acidic media. However, Pt-based catalysts have high cost and are easily deactivated by CO poisoning. Therefore, novel catalysts have been developed, and among then, palladium-based materials have shown promising results for the oxidation of ethanol in alkaline media. The present study reports on the performance of alkaline direct ethanol fuel cell (ADEFC) by using carbon-supported Pd, PdSn, PdNi, and PdNiSn produced by impregnation-reduction of the metallic precursors. The effect of chemical functionalization by acid treatment of the carbon support (Vulcan) was investigated. The electrocatalysts were studied by thermogravimetric analysis (TGA), X-rays diffraction (XRD), transmission electron microscopy (TEM), cyclic voltammetry (CV), and ADEFC tests. TGA measurements of functionalized Vulcan evidenced the characteristic weight losses attributed to the presence of surface functional groups due to the acid treatment. A high degree of alloying between Pd and Sn was inferred from XRD data, whereas in both PdNi and PdNiSn, Ni occurs mostly segregated in the oxide form. TEM analyses indicated agglomeration of Pd and PdSn particles, whereas a more uniform particle distribution was observed for PdNi and PdNiSn samples. CV curves showed that the peak potential for the oxidation of ethanol shifts towards negative values for all samples supported on functionalized Vulcan indicating that ethanol oxidation is facilitated. Microstructural and electrochemical features were confirmed by ADEFC tests, which revealed that the highest open circuit voltage and maximum power density were achieved for PdNiSn electrocatalysts supported on functionalized Vulcan with uniform particle distribution and improved triple phase boundaries. (author)

Palladium-based electrocatalysts for ethanol oxidation reaction in alkaline direct ethanol fuel cell

International Nuclear Information System (INIS)

Moraes, Leticia Poras Reis de; Amico, Sandro Campos; Malfatti, Celia de Fraga; Matos, Bruno R.; Santiago, Elisabete Inacio; Fonseca, Fabio Coral

2016-01-01

Full text: Direct ethanol fuel cells require adequate electrocatalysts to promote the carbon carbon cleavage of ethanol molecule. Typical electrocatalysts are based on platinum, which have shown improved activity in acidic media. However, Pt-based catalysts have high cost and are easily deactivated by CO poisoning. Therefore, novel catalysts have been developed, and among then, palladium-based materials have shown promising results for the oxidation of ethanol in alkaline media. The present study reports on the performance of alkaline direct ethanol fuel cell (ADEFC) by using carbon-supported Pd, PdSn, PdNi, and PdNiSn produced by impregnation-reduction of the metallic precursors. The effect of chemical functionalization by acid treatment of the carbon support (Vulcan) was investigated. The electrocatalysts were studied by thermogravimetric analysis (TGA), X-rays diffraction (XRD), transmission electron microscopy (TEM), cyclic voltammetry (CV), and ADEFC tests. TGA measurements of functionalized Vulcan evidenced the characteristic weight losses attributed to the presence of surface functional groups due to the acid treatment. A high degree of alloying between Pd and Sn was inferred from XRD data, whereas in both PdNi and PdNiSn, Ni occurs mostly segregated in the oxide form. TEM analyses indicated agglomeration of Pd and PdSn particles, whereas a more uniform particle distribution was observed for PdNi and PdNiSn samples. CV curves showed that the peak potential for the oxidation of ethanol shifts towards negative values for all samples supported on functionalized Vulcan indicating that ethanol oxidation is facilitated. Microstructural and electrochemical features were confirmed by ADEFC tests, which revealed that the highest open circuit voltage and maximum power density were achieved for PdNiSn electrocatalysts supported on functionalized Vulcan with uniform particle distribution and improved triple phase boundaries. (author)

Chronic intermittent ethanol exposure in early adolescent and adult male rats: effects on tolerance, social behavior, and ethanol intake.

Science.gov (United States)

Broadwater, Margaret; Varlinskaya, Elena I; Spear, Linda P

2011-08-01

Given the prevalence of alcohol use in adolescence, it is important to understand the consequences of chronic ethanol exposure during this critical period in development. The purpose of this study was to assess possible age-related differences in susceptibility to tolerance development to ethanol-induced sedation and withdrawal-related anxiety, as well as voluntary ethanol intake after chronic exposure to relatively high doses of ethanol during adolescence or adulthood. Juvenile/adolescent and adult male Sprague-Dawley rats were assigned to one of five 10-day exposure conditions: chronic ethanol (4 g/kg every 48 hours), chronic saline (equivalent volume every 24 hours), chronic saline/acutely challenged with ethanol (4 g/kg on day 10), nonmanipulated/acutely challenged with ethanol (4 g/kg on day 10), or nonmanipulated. For assessment of tolerance development, duration of the loss of righting reflex (LORR) and blood ethanol concentrations (BECs) upon regaining of righting reflex (RORR) were tested on the first and last ethanol exposure days in the chronic ethanol group, with both saline and nonmanipulated animals likewise challenged on the last exposure day. Withdrawal-induced anxiety was indexed in a social interaction test 24 hours after the last ethanol exposure, with ethanol-naïve chronic saline and nonmanipulated animals serving as controls. Voluntary intake was assessed 48 hours after the chronic exposure period in chronic ethanol, chronic saline and nonmanipulated animals using an 8-day 2 bottle choice, limited-access ethanol intake procedure. In general, adolescent animals showed shorter durations of LORR and higher BECs upon RORR than adults on the first and last ethanol exposure days, regardless of chronic exposure condition. Adults, but not adolescents, developed chronic tolerance to the sedative effects of ethanol, tolerance that appeared to be metabolic in nature. Social deficits were observed after chronic ethanol in both adolescents and adults

Enhancement of gamma-ray-induced mutation frequency in rice by post-treatment with chloral hydrate, methanol and their mixtures with ethanol

International Nuclear Information System (INIS)

Reddy, T.P.; Vaidyanath, K.

1979-01-01

An evaluation has been made of the mutagenic activity of ethanol, chlorate hydrate (CH) and methanol on rice seed. In independent treatments with ethanol, methanol, CH and four aqueous mixtures of these chemicals, chlorophyll-deficient mutants were not recovered in the M 2 generation. However, in sequential treatments with gamma rays + CH, gamma rays + methanol and gamma rays + aqueous mixtures of these chemicals, significant increases in the yields of chlorophyll mutations were observed as compared to that of a 30 kR gamma ray treatment. In contrast, post-irradiation treatment with ethanol failed to provoke any increase in the frequency of chlorophyll mutants in the M 2 generation. The results indicate that CH and methanol alone and mixed with ethanol can potentiate gamma ray-induced genetic lesions in rice seed. (author)

Chronic plus binge ethanol exposure causes more severe pancreatic injury and inflammation

Energy Technology Data Exchange (ETDEWEB)

Ren, Zhenhua [Department of Anatomy, School of Basic Medicine, Anhui Medical University, Hefei, Anhui, China 230032 (China); Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536 (United States); Yang, Fanmuyi; Wang, Xin; Wang, Yongchao; Xu, Mei; Frank, Jacqueline A. [Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536 (United States); Ke, Zun-ji [Department of Biochemistry, Shanghai University of Traditional Chinese Medicine, Shanghai 201203 (China); Zhang, Zhuo; Shi, Xianglin [Department of Toxicology and Cancer Biology, University of Kentucky College of Medicine, Lexington, KY 40536 (United States); Luo, Jia, E-mail: jialuo888@uky.edu [Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536 (United States)

2016-10-01

Alcohol abuse increases the risk for pancreatitis. The pattern of alcohol drinking may impact its effect. We tested a hypothesis that chronic ethanol consumption in combination with binge exposure imposes more severe damage to the pancreas. C57BL/6 mice were divided into four groups: control, chronic ethanol exposure, binge ethanol exposure and chronic plus binge ethanol exposure. For the control group, mice were fed with a liquid diet for two weeks. For the chronic ethanol exposure group, mice were fed with a liquid diet containing 5% ethanol for two weeks. In the binge ethanol exposure group, mice were treated with ethanol by gavage (5 g/kg, 25% ethanol w/v) daily for 3 days. For the chronic plus binge exposure group, mice were fed with a liquid diet containing 5% ethanol for two weeks and exposed to ethanol by gavage during the last 3 days. Chronic and binge exposure alone caused minimal pancreatic injury. However, chronic plus binge ethanol exposure induced significant apoptotic cell death. Chronic plus binge ethanol exposure altered the levels of alpha-amylase, glucose and insulin. Chronic plus binge ethanol exposure caused pancreatic inflammation which was shown by the macrophages infiltration and the increase of cytokines and chemokines. Chronic plus binge ethanol exposure increased the expression of ADH1 and CYP2E1. It also induced endoplasmic reticulum stress which was demonstrated by the unfolded protein response. In addition, chronic plus binge ethanol exposure increased protein oxidation and lipid peroxidation, indicating oxidative stress. Therefore, chronic plus binge ethanol exposure is more detrimental to the pancreas. - Highlights: • Chronic plus binge alcohol drinking causes more pancreatic injury. • Chronic plus binge alcohol drinking induces more pancreatic inflammation. • Chronic plus binge alcohol causes more endoplasmic reticulum stress and oxidative stress.

Chronic plus binge ethanol exposure causes more severe pancreatic injury and inflammation

International Nuclear Information System (INIS)

Ren, Zhenhua; Yang, Fanmuyi; Wang, Xin; Wang, Yongchao; Xu, Mei; Frank, Jacqueline A.; Ke, Zun-ji; Zhang, Zhuo; Shi, Xianglin; Luo, Jia

2016-01-01

Alcohol abuse increases the risk for pancreatitis. The pattern of alcohol drinking may impact its effect. We tested a hypothesis that chronic ethanol consumption in combination with binge exposure imposes more severe damage to the pancreas. C57BL/6 mice were divided into four groups: control, chronic ethanol exposure, binge ethanol exposure and chronic plus binge ethanol exposure. For the control group, mice were fed with a liquid diet for two weeks. For the chronic ethanol exposure group, mice were fed with a liquid diet containing 5% ethanol for two weeks. In the binge ethanol exposure group, mice were treated with ethanol by gavage (5 g/kg, 25% ethanol w/v) daily for 3 days. For the chronic plus binge exposure group, mice were fed with a liquid diet containing 5% ethanol for two weeks and exposed to ethanol by gavage during the last 3 days. Chronic and binge exposure alone caused minimal pancreatic injury. However, chronic plus binge ethanol exposure induced significant apoptotic cell death. Chronic plus binge ethanol exposure altered the levels of alpha-amylase, glucose and insulin. Chronic plus binge ethanol exposure caused pancreatic inflammation which was shown by the macrophages infiltration and the increase of cytokines and chemokines. Chronic plus binge ethanol exposure increased the expression of ADH1 and CYP2E1. It also induced endoplasmic reticulum stress which was demonstrated by the unfolded protein response. In addition, chronic plus binge ethanol exposure increased protein oxidation and lipid peroxidation, indicating oxidative stress. Therefore, chronic plus binge ethanol exposure is more detrimental to the pancreas. - Highlights: • Chronic plus binge alcohol drinking causes more pancreatic injury. • Chronic plus binge alcohol drinking induces more pancreatic inflammation. • Chronic plus binge alcohol causes more endoplasmic reticulum stress and oxidative stress.

Vanillin abrogates ethanol induced gastric injury in rats via modulation of gastric secretion, oxidative stress and inflammation.

Science.gov (United States)

Al Asmari, Abdulrahman; Al Shahrani, Hamoud; Al Masri, Nasser; Al Faraidi, Ahmed; Elfaki, Ibrahim; Arshaduddin, Mohammed

2016-01-01

Vanillin is commonly used as an additive in food, medicine and cosmetics, but its effect has not yet been studied in gastric injury. Therefore the effect of vanillin was studied in experimental gastric ulcer. Gastric secretion and acidity were studied in pylorus ligated rats. Ulcer index, levels of gastric mucus, malondialdehyde (MDA), myeloperoxidase activity (MPO), expression of nuclear factor kappa B (NF-κB) p65, and histopathological changes were determined in ethanol induced gastric ulcer. Pre treatment with vanillin significantly reduced gastric secretion ( P  Vanillin significantly restored the depleted gastric wall mucus levels ( P  Vanillin was also effective in alleviating the damage to the histological architecture and the activation of mast cells induced by ethanol. Together the results of this study highlight the gastroprotective activity of vanillin in gastric ulcers of rats through multiple actions that include inhibition of gastric secretion and acidity, reduction of inflammation and oxidative stress, suppression of expression of NF-κB, and restoration of the histological architecture.

Moderate Ethanol Preconditioning of Rat Brain Cultures Engenders Neuroprotection Against Dementia-Inducing Neuroinflammatory Proteins: Possible Signaling Mechanisms

Science.gov (United States)

Neafsey, Edward J.; Wang, Kewei; Achille, Nicholas J.; Mitchell, Robert M.; Sivaswamy, Sreevidya

2010-01-01

There is no question that chronic alcohol (ethanol) abuse, a leading worldwide problem, causes neuronal dysfunction and brain damage. However, various epidemiologic studies in recent years have indicated that in comparisons with abstainers or never-drinkers, light/moderate alcohol consumers have lower risks of age-dependent cognitive decline and/or dementia, including Alzheimer’s disease (AD). Such reduced risks have been variously attributed to favorable circulatory and/or cerebrovascular effects of moderate ethanol intake, but they could also involve ethanol “preconditioning” phenomena in brain glia and neurons. Here we summarize our experimental studies showing that moderate ethanol preconditioning (MEP; 20–30 mM ethanol) of rat brain cultures prevents neurodegeneration due to β-amyloid, an important protein implicated in AD, and to other neuroinflammatory proteins such as gp120, the human immunodeficiency virus 1 envelope protein linked to AIDS dementia. The MEP neuroprotection is associated with suppression of neurotoxic protein-evoked initial increases in [Ca+2]i and proinflammatory mediators—e.g., superoxide anion, arachidonic acid, and glutamate. Applying a sensor → transducer → effector model to MEP, we find that onset of neuroprotection correlates temporally with elevations in “effector” heat shock proteins (HSP70, HSP27, and phospho-HSP27). The effector status of HSPs is supported by the fact that inhibiting HSP elevations due to MEP largely restores gp120-induced superoxide potentiation and subsequent neurotoxicity. As upstream mediators, synaptic N-methyl-d-aspartate receptors may be initial prosurvival sensors of ethanol, and protein kinase C epsilon and focal adhesion kinase are likely transducers during MEP that are essential for protective HSP elevations. Regarding human consumption, we speculate that moderate ethanol intake might counter incipient cognitive deterioration during advanced aging or AD by exerting preconditioning

Moderate ethanol preconditioning of rat brain cultures engenders neuroprotection against dementia-inducing neuroinflammatory proteins: possible signaling mechanisms.

Science.gov (United States)

Collins, Michael A; Neafsey, Edward J; Wang, Kewei; Achille, Nicholas J; Mitchell, Robert M; Sivaswamy, Sreevidya

2010-06-01

There is no question that chronic alcohol (ethanol) abuse, a leading worldwide problem, causes neuronal dysfunction and brain damage. However, various epidemiologic studies in recent years have indicated that in comparisons with abstainers or never-drinkers, light/moderate alcohol consumers have lower risks of age-dependent cognitive decline and/or dementia, including Alzheimer's disease (AD). Such reduced risks have been variously attributed to favorable circulatory and/or cerebrovascular effects of moderate ethanol intake, but they could also involve ethanol "preconditioning" phenomena in brain glia and neurons. Here we summarize our experimental studies showing that moderate ethanol preconditioning (MEP; 20-30 mM ethanol) of rat brain cultures prevents neurodegeneration due to beta-amyloid, an important protein implicated in AD, and to other neuroinflammatory proteins such as gp120, the human immunodeficiency virus 1 envelope protein linked to AIDS dementia. The MEP neuroprotection is associated with suppression of neurotoxic protein-evoked initial increases in [Ca(+2)](i) and proinflammatory mediators--e.g., superoxide anion, arachidonic acid, and glutamate. Applying a sensor --> transducer --> effector model to MEP, we find that onset of neuroprotection correlates temporally with elevations in "effector" heat shock proteins (HSP70, HSP27, and phospho-HSP27). The effector status of HSPs is supported by the fact that inhibiting HSP elevations due to MEP largely restores gp120-induced superoxide potentiation and subsequent neurotoxicity. As upstream mediators, synaptic N-methyl-d-aspartate receptors may be initial prosurvival sensors of ethanol, and protein kinase C epsilon and focal adhesion kinase are likely transducers during MEP that are essential for protective HSP elevations. Regarding human consumption, we speculate that moderate ethanol intake might counter incipient cognitive deterioration during advanced aging or AD by exerting preconditioning

Anti-inflammatory effect of bee pollen ethanol extract from Cistus sp. of Spanish on carrageenan-induced rat hind paw edema

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Araki Yoko

2010-06-01

Full Text Available Abstract Background Bee pollen, a honeybee product, is the feed for honeybees prepared themselves by pollens collecting from plants and has been consumed as a perfect food in Europe, because it is nutritionally well balanced. In this study, we aimed to investigate the anti-inflammatory effect of bee pollen from Cistus sp. of Spanish origin by a method of carrageenan-induced paw edema in rats, and to investigate the mechanism of anti-inflammatory action and also to elucidate components involved in bee pollen extracted with ethanol. Methods The bee pollen bulk, its water extract and its ethanol extract were administered orally to rats. One hour later, paw edema was produced by injecting of 1% solution of carrageenan, and paw volume was measured before and after carrageenan injection up to 5 h. The ethanol extract and water extract were measured COX-1 and COX-2 inhibitory activities using COX inhibitor screening assay kit, and were compared for the inhibition of NO production in LPS-stimulated RAW 264.7 cells. The constituents of bee pollen were purified from the ethanol extract subjected to silica gel or LH-20 column chromatography. Each column chromatography fractions were further purified by repeated ODS or silica gel column chromatography. Results The bee pollen bulk mildly suppressed the carrageenan-induced paw edema and the water extract showed almost no inhibitory activity, but the ethanol extract showed relatively strong inhibition of paw edema. The ethanol extract inhibited the NO production and COX-2 but not COX-1 activity, but the water extract did not affect the NO production or COX activities. Flavonoids were isolated and purified from the ethanol extract of bee pollen, and identified at least five flavonoids and their glycosides. Conclusions It is suggested that the ethanol extract of bee pollen show a potent anti-inflammatory activity and its effect acts via the inhibition of NO production, besides the inhibitory activity of COX-2

Adenylyl cylases 1 and 8 mediate select striatal-dependent behaviors and sensitivity to ethanol stimulation in the adolescent period following acute neonatal ethanol exposure.

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Susick, Laura L; Lowing, Jennifer L; Bosse, Kelly E; Hildebrandt, Clara C; Chrumka, Alexandria C; Conti, Alana C

2014-08-01

Neonatal alcohol exposure in rodents causes dramatic neurodegenerative effects throughout the developing nervous system, particularly in the striatum, acutely after exposure. These acute neurodegenerative effects are augmented in mice lacking adenylyl cyclases 1 and 8 (AC1/8) as neonatal mice with a genetic deletion of both AC isoforms (DKO) have increased vulnerability to ethanol-induced striatal neurotoxicity compared to wild type (WT) controls. While neonatal ethanol exposure is known to negatively impact cognitive behaviors, such as executive functioning and working memory in adolescent and adult animals, the threshold of ethanol exposure required to impinge upon developmental behaviors in mice has not been extensively examined. Therefore, the purpose of this study was to determine the behavioral effects of neonatal ethanol exposure using various striatal-dependent developmental benchmarks and to assess the impact of AC1/8 deletion on this developmental progression. WT and DKO mice were treated with 2.5 g/kg ethanol or saline on postnatal day (P)6 and later subjected to the wire suspension, negative geotaxis, postural reflex, grid hang, tail suspension and accelerating rotarod tests at various time points. At P30, mice were evaluated for their hypnotic responses to 4.0 g/kg ethanol by using the loss of righting reflex assay and ethanol-induced stimulation of locomotor activity after 2.0 g/kg ethanol. Ethanol exposure significantly impaired DKO performance in the negative geotaxis test while genetic deletion of AC1/8 alone increased grid hang time and decreased immobility time in the tail suspension test with a concomitant increase in hindlimb clasping behavior. Locomotor stimulation was significantly increased in animals that received ethanol as neonates, peaking significantly in ethanol-treated DKO mice compared to ethanol-treated WT controls, while sedation duration following high-dose ethanol challenge was unaffected. These data indicate that the

Strawberry polyphenols attenuate ethanol-induced gastric lesions in rats by activation of antioxidant enzymes and attenuation of MDA increase.

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José M Alvarez-Suarez

Full Text Available BACKGROUND AND AIM: Free radicals are implicated in the aetiology of gastrointestinal disorders such as gastric ulcer, colorectal cancer and inflammatory bowel disease. Strawberries are common and important fruit due to their high content of essential nutrient and beneficial phytochemicals which seem to have relevant biological activity on human health. In the present study we investigated the antioxidant and protective effects of three strawberry extracts against ethanol-induced gastric mucosa damage in an experimental in vivo model and to test whether strawberry extracts affect antioxidant enzyme activities in gastric mucosa. METHODS/PRINCIPAL FINDINGS: Strawberry extracts were obtained from Adria, Sveva and Alba cultivars. Total antioxidant capacity and radical scavenging capacity were performed by TEAC, ORAC and electron paramagnetic resonance assays. Identification and quantification of anthocyanins was carried out by HPLC-DAD-MS analyses. Different groups of animals received 40 mg/day/kg body weight of strawberry crude extracts for 10 days. Gastric damage was induced by ethanol. The ulcer index was calculated together with the determination of catalase and SOD activities and MDA contents. Strawberry extracts are rich in anthocyanins and present important antioxidant capacity. Ethanol caused severe gastric damage and strawberry consumption protected against its deleterious role. Antioxidant enzyme activities increased significantly after strawberry extract intake and a concomitantly decrease in gastric lipid peroxidation was found. A significant correlation between total anthocyanin content and percent of inhibition of ulcer index was also found. CONCLUSIONS: Strawberry extracts prevented exogenous ethanol-induced damage to rats' gastric mucosa. These effects seem to be associated with the antioxidant activity and phenolic content in the extract as well as with the capacity of promoting the action of antioxidant enzymes. A diet rich in

Strawberry Polyphenols Attenuate Ethanol-Induced Gastric Lesions in Rats by Activation of Antioxidant Enzymes and Attenuation of MDA Increase

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Alvarez-Suarez, José M.; Dekanski, Dragana; Ristić, Slavica; Radonjić, Nevena V.; Petronijević, Nataša D.; Giampieri, Francesca; Astolfi, Paola; González-Paramás, Ana M.; Santos-Buelga, Celestino; Tulipani, Sara; Quiles, José L.; Mezzetti, Bruno; Battino, Maurizio

2011-01-01

Background and Aim Free radicals are implicated in the aetiology of gastrointestinal disorders such as gastric ulcer, colorectal cancer and inflammatory bowel disease. Strawberries are common and important fruit due to their high content of essential nutrient and beneficial phytochemicals which seem to have relevant biological activity on human health. In the present study we investigated the antioxidant and protective effects of three strawberry extracts against ethanol-induced gastric mucosa damage in an experimental in vivo model and to test whether strawberry extracts affect antioxidant enzyme activities in gastric mucosa. Methods/Principal Findings Strawberry extracts were obtained from Adria, Sveva and Alba cultivars. Total antioxidant capacity and radical scavenging capacity were performed by TEAC, ORAC and electron paramagnetic resonance assays. Identification and quantification of anthocyanins was carried out by HPLC-DAD-MS analyses. Different groups of animals received 40 mg/day/kg body weight of strawberry crude extracts for 10 days. Gastric damage was induced by ethanol. The ulcer index was calculated together with the determination of catalase and SOD activities and MDA contents. Strawberry extracts are rich in anthocyanins and present important antioxidant capacity. Ethanol caused severe gastric damage and strawberry consumption protected against its deleterious role. Antioxidant enzyme activities increased significantly after strawberry extract intake and a concomitantly decrease in gastric lipid peroxidation was found. A significant correlation between total anthocyanin content and percent of inhibition of ulcer index was also found. Conclusions Strawberry extracts prevented exogenous ethanol-induced damage to rats' gastric mucosa. These effects seem to be associated with the antioxidant activity and phenolic content in the extract as well as with the capacity of promoting the action of antioxidant enzymes. A diet rich in strawberries might exert a

The protective activity of Conyza blinii saponin against acute gastric ulcer induced by ethanol.

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Ma, Long; Liu, Jiangguang

2014-12-02

Conyza blinii H.Lév., is a type of natural plant. Its dried overground section is used to treat infections and inflammations in traditional Chinese medicine. Triterpenoidal saponins have a wide range of bioactivities, for instance, anti-cancer, anti-virus and anti-anaphylaxis. Conyza blinii saponin (CBS), mainly composed of triterpenoidal saponins, is the total saponin of Conyza blinii H.Lév. It has been reported that CBS also has gastric mucous membrane protection activity. This study aims to test CBS׳s protective activity of gastric׳s mucous membrane against ethanol. This investigation may lead to the development of novel drug from natural products as anti-ulcer agent, or as gastric mucous protective against chemical damage. CBS (Conyza blinii saponin) is the total saponin of Conyza blinii H.Lév., which was obtained as described previously. We tested the protective activity of CBS against ethanol-induced ulcer. Thirty six rats were grouped randomly as 'NORMAL', 'CONTROL', 'MODEL', 'LOW DOSE', 'MEDIUM DOSE' and 'HIGH DOSE'. The 'NORMAL' group were rats with no pathological model established within it. The 'CONTROL' group was administrated with colloidal bismuth subcitrate, while 'MODEL' group was not given any active agents apart from absolute ethanol in order to obtain gastric ulcer model. The three 'DOSE' groups were treated with different concentrations of CBS (5, 10, 20mg/mL) before administration followed by absolute ethanol. All rats were sacrificed after the experiment to acquire the gastric tissue. The ulcer index (UI), malondialdehyde (MDA) and superoxide dismutase (SOD) were measured to monitor the activity of CBS. Besides, the rat gastric tissue was made to paraffin section and stained using the Hematoxylin-Eosin (HE) method. The histopathology examination was carried out to examine CBS efficacy in terms of gastric mucous protection. We found that CBS had a profound protection activity against acute gastric ulcer induced by ethanol and this

Evaluation of hepatoprotective activity of aqueous and ethanolic extract of Oxalis corniculata against intoxication of thioacetamide induced rats

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Kuntal Das

2012-04-01

Full Text Available The present study was carried out to evaluate the hepatoprotective activity of aqueous and ethanolic leaves extracts of Oxalis corniculata L., Oxalidaceae, against thioacetamide-induced hepatotoxicity. Hepatotoxicity was induced in Wistar rats of either sex by subcutaneous injection of thioacetamide. An aqueous and ethanolic extract of aerial parts of O. corniculata (200 and 400 mg/kg/day were evaluated. Oral administration of O. corniculata aqueous and ethanolic leaves extract at 400 mg/kg resulted in a significant reduction in SGOT (146.42±2.54 and 136.75±1.37 IU/L respectively, SGPT (81.96±3.15 and 72.05±2.33 IU/L respectively, GGTP (16.6±0.49 and 15.02±0.68 IU/L respectively, ALP (241.86±3.94 and 202.42±5.37 IU/L respectively and total bilirubin (0.226±0.00 mg/dL 0.288±0.01 mg/dL respectively content that were lesser than positive control, thioacetamide damaged rats. Histology of the liver sections of the animals treated with the extract also showed dose dependent reduction of necrosis. Hence the study concluded that O. corniculata has potential hepatoprotective activity.

Evaluation of hepatoprotective activity of aqueous and ethanolic extract of Oxalis corniculata against intoxication of thioacetamide induced rats

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Kuntal Das

2011-10-01

Full Text Available The present study was carried out to evaluate the hepatoprotective activity of aqueous and ethanolic leaves extracts of Oxalis corniculata L., Oxalidaceae, against thioacetamide-induced hepatotoxicity. Hepatotoxicity was induced in Wistar rats of either sex by subcutaneous injection of thioacetamide. An aqueous and ethanolic extract of aerial parts of O. corniculata (200 and 400 mg/kg/day were evaluated. Oral administration of O. corniculata aqueous and ethanolic leaves extract at 400 mg/kg resulted in a significant reduction in SGOT (146.42±2.54 and 136.75±1.37 IU/L respectively, SGPT (81.96±3.15 and 72.05±2.33 IU/L respectively, GGTP (16.6±0.49 and 15.02±0.68 IU/L respectively, ALP (241.86±3.94 and 202.42±5.37 IU/L respectively and total bilirubin (0.226±0.00 mg/dL 0.288±0.01 mg/dL respectively content that were lesser than positive control, thioacetamide damaged rats. Histology of the liver sections of the animals treated with the extract also showed dose dependent reduction of necrosis. Hence the study concluded that O. corniculata has potential hepatoprotective activity.

Protective effect of the leaves of Vitex negundo against ethanol ...

African Journals Online (AJOL)

The present study investigated the effect of the various fractions of hydromethanolic extract of the leaves of Vitex negundo (Verbenaceae) against ethanol-induced cerebral oxidative stress in rats. Cerebral oxidative stress was induced by the administration of 20% ethanol (5 ml/100g bw) for a period of 28 days.

Temperature dependence of heat sensitization and thermotolerance induction with ethanol

International Nuclear Information System (INIS)

Henle, K.J.; Nagle, W.A.; Moss, A.J.

1987-01-01

Cytoxicity of 1 M ethanol was strongly temperature dependent; survival curves between 34 0 and 39 0 C were similar to heat survival curves between 40 and 45 0 without ethanol. Ethanol was non-toxic at 22 0 ; at 34.5 0 and 35.5 0 ethanol survival curves were biphasic. The major effect of 1 M ethanol was an effective temperature shift of 6.4 Celsius degrees, although temperatures between 34 0 and 36 0 caused additional sensitization reminiscent of the stepdown heating phenomenon. Induction of thermotolerance with equitoxic ethanol exposures at 35.5 0 and 37 0 or with heat alone (10 min, 45 0 ) resulted in tolerance development with similar kinetics; in contrast, ethanol exposures at 22 0 did not induce any tolerance development with similar kinetics; in contrast, ethanol exposures at 22 0 did not induce any tolerance to hyperthermia. These data provide a rationale for conflicting reports in the literature regarding thermotolerance induction by ethanol and suggest that ethanol causes ''heat'' stress at temperatures that are generally considered to be physiological. This interpretation predicts that the use of ethanol and other organic solvents in high concentrations will cause effects at 37 0 that normally occur only at hyperthermic temperatures, including membrane perturbations and HSP synthesis, and that ''physiological'' temperatures must be precisely controlled under those conditions

Grapefruit-seed extract attenuates ethanol-and stress-induced gastric lesions via activation of prostaglandin, nitric oxide and sensory nerve pathways

OpenAIRE

Brzozowski, Tomasz; Konturek, Peter C; Drozdowicz, Danuta; Konturek, Stanislaw J; Zayachivska, Oxana; Pajdo, Robert; Kwiecien, Slawomir; Pawlik, Wieslaw W; Hahn, Eckhart G

2005-01-01

AIM: Grapefruit-seed extract (GSE) containing flavonoids, possesses antibacterial and antioxidative properties but whether it influences the gastric defense mechanism and gastroprotection against ethanol- and stress-induced gastric lesions remains unknown.

Evidence for a Role for the Plasma Membrane in the Nanomechanical Properties of the Cell Wall as Revealed by an Atomic Force Microscopy Study of the Response of Saccharomyces cerevisiae to Ethanol Stress.

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Schiavone, Marion; Formosa-Dague, Cécile; Elsztein, Carolina; Teste, Marie-Ange; Martin-Yken, Helene; De Morais, Marcos A; Dague, Etienne; François, Jean M

2016-08-01

A wealth of biochemical and molecular data have been reported regarding ethanol toxicity in the yeast Saccharomyces cerevisiae However, direct physical data on the effects of ethanol stress on yeast cells are almost nonexistent. This lack of information can now be addressed by using atomic force microscopy (AFM) technology. In this report, we show that the stiffness of glucose-grown yeast cells challenged with 9% (vol/vol) ethanol for 5 h was dramatically reduced, as shown by a 5-fold drop of Young's modulus. Quite unexpectedly, a mutant deficient in the Msn2/Msn4 transcription factor, which is known to mediate the ethanol stress response, exhibited a low level of stiffness similar to that of ethanol-treated wild-type cells. Reciprocally, the stiffness of yeast cells overexpressing MSN2 was about 35% higher than that of the wild type but was nevertheless reduced 3- to 4-fold upon exposure to ethanol. Based on these and other data presented herein, we postulated that the effect of ethanol on cell stiffness may not be mediated through Msn2/Msn4, even though this transcription factor appears to be a determinant in the nanomechanical properties of the cell wall. On the other hand, we found that as with ethanol, the treatment of yeast with the antifungal amphotericin B caused a significant reduction of cell wall stiffness. Since both this drug and ethanol are known to alter, albeit by different means, the fluidity and structure of the plasma membrane, these data led to the proposition that the cell membrane contributes to the biophysical properties of yeast cells. Ethanol is the main product of yeast fermentation but is also a toxic compound for this process. Understanding the mechanism of this toxicity is of great importance for industrial applications. While most research has focused on genomic studies of ethanol tolerance, we investigated the effects of ethanol at the biophysical level and found that ethanol causes a strong reduction of the cell wall rigidity (or

Evidence for a Role for the Plasma Membrane in the Nanomechanical Properties of the Cell Wall as Revealed by an Atomic Force Microscopy Study of the Response of Saccharomyces cerevisiae to Ethanol Stress

Science.gov (United States)

Schiavone, Marion; Formosa-Dague, Cécile; Elsztein, Carolina; Teste, Marie-Ange; Martin-Yken, Helene; De Morais, Marcos A.; Dague, Etienne

2016-01-01

ABSTRACT A wealth of biochemical and molecular data have been reported regarding ethanol toxicity in the yeast Saccharomyces cerevisiae. However, direct physical data on the effects of ethanol stress on yeast cells are almost nonexistent. This lack of information can now be addressed by using atomic force microscopy (AFM) technology. In this report, we show that the stiffness of glucose-grown yeast cells challenged with 9% (vol/vol) ethanol for 5 h was dramatically reduced, as shown by a 5-fold drop of Young's modulus. Quite unexpectedly, a mutant deficient in the Msn2/Msn4 transcription factor, which is known to mediate the ethanol stress response, exhibited a low level of stiffness similar to that of ethanol-treated wild-type cells. Reciprocally, the stiffness of yeast cells overexpressing MSN2 was about 35% higher than that of the wild type but was nevertheless reduced 3- to 4-fold upon exposure to ethanol. Based on these and other data presented herein, we postulated that the effect of ethanol on cell stiffness may not be mediated through Msn2/Msn4, even though this transcription factor appears to be a determinant in the nanomechanical properties of the cell wall. On the other hand, we found that as with ethanol, the treatment of yeast with the antifungal amphotericin B caused a significant reduction of cell wall stiffness. Since both this drug and ethanol are known to alter, albeit by different means, the fluidity and structure of the plasma membrane, these data led to the proposition that the cell membrane contributes to the biophysical properties of yeast cells. IMPORTANCE Ethanol is the main product of yeast fermentation but is also a toxic compound for this process. Understanding the mechanism of this toxicity is of great importance for industrial applications. While most research has focused on genomic studies of ethanol tolerance, we investigated the effects of ethanol at the biophysical level and found that ethanol causes a strong reduction of the cell

Role of interleukin-1 receptor signaling in the behavioral effects of ethanol and benzodiazepines.

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Blednov, Yuri A; Benavidez, Jillian M; Black, Mendy; Mayfield, Jody; Harris, R Adron

2015-08-01

Gene expression studies identified the interleukin-1 receptor type I (IL-1R1) as part of a pathway associated with a genetic predisposition to high alcohol consumption, and lack of the endogenous IL-1 receptor antagonist (IL-1ra) strongly reduced ethanol intake in mice. Here, we compared ethanol-mediated behaviors in mice lacking Il1rn or Il1r1. Deletion of Il1rn (the gene encoding IL-1ra) increases sensitivity to the sedative/hypnotic effects of ethanol and flurazepam and reduces severity of acute ethanol withdrawal. Conversely, deletion of Il1r1 (the gene encoding the IL-1 receptor type I, IL-1R1) reduces sensitivity to the sedative effects of ethanol and flurazepam and increases the severity of acute ethanol withdrawal. The sedative effects of ketamine and pentobarbital were not altered in the knockout (KO) strains. Ethanol intake and preference were not changed in mice lacking Il1r1 in three different tests of ethanol consumption. Recovery from ethanol-induced motor incoordination was only altered in female mice lacking Il1r1. Mice lacking Il1rn (but not Il1r1) showed increased ethanol clearance and decreased ethanol-induced conditioned taste aversion. The increased ethanol- and flurazepam-induced sedation in Il1rn KO mice was decreased by administration of IL-1ra (Kineret), and pre-treatment with Kineret also restored the severity of acute ethanol withdrawal. Ethanol-induced sedation and withdrawal severity were changed in opposite directions in the null mutants, indicating that these responses are likely regulated by IL-1R1 signaling, whereas ethanol intake and preference do not appear to be solely regulated by this pathway. Copyright © 2015 Elsevier Ltd. All rights reserved.

Acute effects of ethanol and acetate on glucose kinetics in normal subjects

International Nuclear Information System (INIS)

Yki-Jaervinen, H.; Koivisto, V.A.; Ylikahri, R.; Taskinen, M.R.

1988-01-01

The authors compared the effects of two ethanol doses on glucose kinetics and assessed the role of acetate as a mediator of ethanol-induced insulin resistance. Ten normal males were studied on four occasions, during which either a low or moderate ethanol, acetate, or saline dose was administered. Both ethanol doses similarly inhibited basal glucose production. The decrease in R a was matched by a comparable decrease in glucose utilization (R d ), resulting in maintenance of normoglycemia. During hyperinsulinemia glucose disposal was lower in the moderate than the low-dose ethanol or saline studies. During acetate infusion, the blood acetate level was comparable with those in the ethanol studies. Acetate had no effect on glucose kinetics. In conclusion, (1) in overnight fasted subjects, ethanol does not cause hypoglycemia because its inhibitory effect on R a is counterbalanced by equal inhibition of R d ; (2) basal R a and R d are maximally inhibited already by small ethanol doses, whereas inhibition of insulin-stimulated glucose disposal requires a moderate ethanol dose; and (3) acetate is not the mediator of ethanol-induced insulin resistance

Chronic intermittent ethanol exposure during adolescence: Effects on stress-induced social alterations and social drinking in adulthood.

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Varlinskaya, Elena I; Kim, Esther U; Spear, Linda P

2017-01-01

We previously observed lasting and sex-specific detrimental consequences of early adolescent intermittent ethanol exposure (AIE), with male, but not female, rats showing social anxiety-like alterations when tested as adults. The present study used Sprague Dawley rats to assess whether social alterations induced by AIE (3.5g/kg, intragastrically, every other day, between postnatal days [P] 25-45) are further exacerbated by stressors later in life. Another aim was to determine whether AIE alone or in combination with stress influenced intake of a sweetened ethanol solution (Experiment 1) or a sweetened solution ("supersac") alone (Experiment 2) under social circumstances. Animals were exposed to restraint on P66-P70 (90min/day) or left nonstressed, with corticosterone (CORT) levels assessed on day 1 and day 5 in Experiment 2. Social anxiety-like behavior emerged after AIE in non-stressed males, but not females, whereas stress-induced social anxiety was evident only in water-exposed males and females. Adult-typical habituation of the CORT response to repeated restraint was not evident in adult animals after AIE, a lack of habituation reminiscent of that normally evident in adolescents. Neither AIE nor stress affected ethanol intake under social circumstances, although AIE and restraint independently increased adolescent-typical play fighting in males during social drinking. Among males, the combination of AIE and restraint suppressed "supersac" intake; this index of depression-like behavior was not seen in females. The results provide experimental evidence associating adolescent alcohol exposure, later stress, anxiety, and depression, with young adolescent males being particularly vulnerable to long-lasting adverse effects of repeated ethanol. This article is part of a Special Issue entitled SI: Adolescent plasticity. Copyright © 2016 Elsevier B.V. All rights reserved.

Forced swim stress increases ethanol consumption in C57BL/6J mice with a history of chronic intermittent ethanol exposure.

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Anderson, Rachel I; Lopez, Marcelo F; Becker, Howard C

2016-06-01

Stress exposure has been identified as one risk factor for alcohol abuse that may facilitate the transition from social or regulated alcohol use to the development of alcohol dependence. Additionally, stress is a common trigger for relapse and subsequent loss of control of drinking in alcohol-dependent individuals. The present study was designed to characterize effects of repeated forced swim stress (FSS) on ethanol consumption in three rodent drinking models that engender high levels of ethanol consumption. Adult male C57BL/6J mice were exposed to 10-min FSS 4 h prior to each drinking session in three different models of high ethanol consumption: chronic intermittent ethanol (CIE) drinking (a model of dependence-like drinking), drinking-in-the-dark (DID; a model of binge-like drinking), and intermittent vs. continuous access (a model of escalated drinking). In the CIE drinking paradigm, daily FSS facilitated the escalation of ethanol intake that is typically seen in CIE-exposed mice without altering ethanol consumption in control mice exposed to FSS. FSS prior to drinking sessions did not alter ethanol consumption in the DID or intermittent access paradigms, whereas stressed mice in the continuous access procedure consumed less ethanol than their nonstressed counterparts. The CIE drinking paradigm may provide a helpful preclinical model of stress-induced transition to ethanol dependence that can be used to (1) identify underlying neural mechanisms that facilitate this transition and (2) evaluate the therapeutic potential of various pharmacological agents hypothesized to alleviate stress-induced drinking.

Anti-fatty liver effects of oils from Zingiber officinale and Curcuma longa on ethanol-induced fatty liver in rats.

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Nwozo, Sarah Onyenibe; Osunmadewa, Damilola Adeola; Oyinloye, Babatunji Emmanuel

2014-01-01

The present study is aimed at evaluating the protective effects of oils from Zingiber officinale (ginger) and Curcuma longa (turmeric) on acute ethanol-induced fatty liver in male Wistar rats. Ferric reducing antioxidant power activity and oxygen radical absorbance capacity of the oils were evaluated ex vivo. Rats were pretreated for 28 d with standard drug (Livolin Forte) and oils from Z. officinale and C. longa before they were exposed to 45% ethanol (4.8 g/kg) to induce acute fatty liver. Histological changes were observed and the degree of protection was measured by using biochemical parameters such as alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase activities. Serum triglyceride (TG) level, total cholesterol (TC) level and the effects of both oils on reduced gluthatione (GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD) and hepatic malondialdehyde (MDA) levels were estimated. Oils from Z. officinale and C. longa at a dose of 200 mg/kg showed hepatoprotection by decreasing the activities of serum enzymes, serum TG, serum TC and hepatic MDA, while they significantly restored the level of GSH as well as GST and SOD activities. Histological examination of rats tissues was related to the obtained results. From the results it may be concluded that oils from Z. officinale and C. longa (200 mg/kg) exhibited hepatoprotective activity in acute ethanol-induced fatty liver and Z. officinale oil was identified to have better effects than C. longa oil.

Junk food diet-induced obesity increases D2 receptor autoinhibition in the ventral tegmental area and reduces ethanol drinking.

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Cook, Jason B; Hendrickson, Linzy M; Garwood, Grant M; Toungate, Kelsey M; Nania, Christina V; Morikawa, Hitoshi

2017-01-01

Similar to drugs of abuse, the hedonic value of food is mediated, at least in part, by the mesostriatal dopamine (DA) system. Prolonged intake of either high calorie diets or drugs of abuse both lead to a blunting of the DA system. Most studies have focused on DAergic alterations in the striatum, but little is known about the effects of high calorie diets on ventral tegmental area (VTA) DA neurons. Since high calorie diets produce addictive-like DAergic adaptations, it is possible these diets may increase addiction susceptibility. However, high calorie diets consistently reduce psychostimulant intake and conditioned place preference in rodents. In contrast, high calorie diets can increase or decrease ethanol drinking, but it is not known how a junk food diet (cafeteria diet) affects ethanol drinking. In the current study, we administered a cafeteria diet consisting of bacon, potato chips, cheesecake, cookies, breakfast cereals, marshmallows, and chocolate candies to male Wistar rats for 3-4 weeks, producing an obese phenotype. Prior cafeteria diet feeding reduced homecage ethanol drinking over 2 weeks of testing, and transiently reduced sucrose and chow intake. Importantly, cafeteria diet had no effect on ethanol metabolism rate or blood ethanol concentrations following 2g/kg ethanol administration. In midbrain slices, we showed that cafeteria diet feeding enhances DA D2 receptor (D2R) autoinhibition in VTA DA neurons. These results show that junk food diet-induced obesity reduces ethanol drinking, and suggest that increased D2R autoinhibition in the VTA may contribute to deficits in DAergic signaling and reward hypofunction observed with obesity.

Chronic ethanol exposure during adolescence in rats induces motor impairments and cerebral cortex damage associated with oxidative stress.

Science.gov (United States)

Teixeira, Francisco Bruno; Santana, Luana Nazaré da Silva; Bezerra, Fernando Romualdo; De Carvalho, Sabrina; Fontes-Júnior, Enéas Andrade; Prediger, Rui Daniel; Crespo-López, Maria Elena; Maia, Cristiane Socorro Ferraz; Lima, Rafael Rodrigues

2014-01-01

Binge drinking is common among adolescents, and this type of ethanol exposure may lead to long-term nervous system damage. In the current study, we evaluated motor performance and tissue alterations in the cerebral cortex of rats subjected to intermittent intoxication with ethanol from adolescence to adulthood. Adolescent male Wistar rats (35 days old) were treated with distilled water or ethanol (6.5 g/kg/day, 22.5% w/v) during 55 days by gavage to complete 90 days of age. The open field, inclined plane and the rotarod tests were used to assess the spontaneous locomotor activity and motor coordination performance in adult animals. Following completion of behavioral tests, half of animals were submitted to immunohistochemical evaluation of NeuN (marker of neuronal bodies), GFAP (a marker of astrocytes) and Iba1 (microglia marker) in the cerebral cortex while the other half of the animals were subjected to analysis of oxidative stress markers by biochemical assays. Chronic ethanol intoxication in rats from adolescence to adulthood induced significant motor deficits including impaired spontaneous locomotion, coordination and muscle strength. These behavioral impairments were accompanied by marked changes in all cellular populations evaluated as well as increased levels of nitrite and lipid peroxidation in the cerebral cortex. These findings indicate that continuous ethanol intoxication from adolescence to adulthood is able to provide neurobehavioral and neurodegenerative damage to cerebral cortex.

A hot water extract of turmeric (Curcuma longa) suppresses acute ethanol-induced liver injury in mice by inhibiting hepatic oxidative stress and inflammatory cytokine production.

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Uchio, Ryusei; Higashi, Yohei; Kohama, Yusuke; Kawasaki, Kengo; Hirao, Takashi; Muroyama, Koutarou; Murosaki, Shinji

2017-01-01

Turmeric ( Curcuma longa ) is a widely used spice that has various biological effects, and aqueous extracts of turmeric exhibit potent antioxidant activity and anti-inflammatory activity. Bisacurone, a component of turmeric extract, is known to have similar effects. Oxidative stress and inflammatory cytokines play an important role in ethanol-induced liver injury. This study was performed to evaluate the influence of a hot water extract of C. longa (WEC) or bisacurone on acute ethanol-induced liver injury. C57BL/6 mice were orally administered WEC (20 mg/kg body weight; BW) or bisacurone (60 µg/kg BW) at 30 min before a single dose of ethanol was given by oral administration (3·0 g/kg BW). Plasma levels of aspartate aminotransferase and alanine aminotransferase were markedly increased in ethanol-treated mice, while the increase of these enzymes was significantly suppressed by prior administration of WEC. The increase of alanine aminotransferase was also significantly suppressed by pretreatment with bisacurone. Compared with control mice, animals given WEC had higher hepatic tissue levels of superoxide dismutase and glutathione, as well as lower hepatic tissue levels of thiobarbituric acid-reactive substances, TNF-α protein and IL-6 mRNA. These results suggest that oral administration of WEC may have a protective effect against ethanol-induced liver injury by suppressing hepatic oxidation and inflammation, at least partly through the effects of bisacurone.

Atomic Layer Deposition of Pd Nanoparticles on TiO₂ Nanotubes for Ethanol Electrooxidation: Synthesis and Electrochemical Properties.

Science.gov (United States)

Assaud, Loïc; Brazeau, Nicolas; Barr, Maïssa K S; Hanbücken, Margrit; Ntais, Spyridon; Baranova, Elena A; Santinacci, Lionel

2015-11-11

Palladium nanoparticles are grown on TiO2 nanotubes by atomic layer deposition (ALD), and the resulting three-dimensional nanostructured catalysts are studied for ethanol electrooxidation in alkaline media. The morphology, the crystal structure, and the chemical composition of the Pd particles are fully characterized using scanning and transmission electron microscopies, X-ray diffraction, and X-ray photoelectron spectroscopy. The characterization revealed that the deposition proceeds onto the entire surface of the TiO2 nanotubes leading to the formation of well-defined and highly dispersed Pd nanoparticles. The electrooxidation of ethanol on Pd clusters deposited on TiO2 nanotubes shows not only a direct correlation between the catalytic activity and the particle size but also a steep increase of the response due to the enhancement of the metal-support interaction when the crystal structure of the TiO2 nanotubes is modified by annealing at 450 °C in air.

Contrast distortion induced by modulation voltage in scanning capacitance microscopy

Science.gov (United States)

Chang, M. N.; Hu, C. W.; Chou, T. H.; Lee, Y. J.

2012-08-01

With a dark-mode scanning capacitance microscopy (SCM), we directly observed the influence of SCM modulation voltage (MV) on image contrasts. For electrical junctions, an extensive modulated area induced by MV may lead to noticeable changes in the SCM signal phase and intensity, resulting in a narrowed junction image and a broadened carrier concentration profile. This contrast distortion in SCM images may occur even if the peak-to-peak MV is down to 0.3 V. In addition, MV may shift the measured electrical junction depth. The balance of SCM signals components explain these MV-induced contrast distortions.

An experimental study on renal infarction with ethanol

International Nuclear Information System (INIS)

Han, Man Chung; Choi, Byung Ihn; Park, Jae Hyung; Ha, Sung Whan; Chang, Kee Hyun

1982-01-01

Renal infarction with ethanol was induced experimentally in rabbits and selective renal angiography was performed to evaluate the effectiveness of ethanol as embolic material. The results were as follows: 1. Complete obstruction of renal artery was produced in all cases within 1 week after injection of absolute ethanol (0.5 ml/Kg). 2. Incomplete obstruction of renal artery was produced in majority after injection of absolute ethanol (0.2 ml/Kg) and changed to complete obstruction above half cases with time. 3. Incomplete obstructive of renal artery was produced in minority after injection of 60% ethanol (0.2 ml/Kg) and complete obstruction of renal artery was not produced. It was consider that ethanol is an effective agent for complete renal infarction and 0.2 to 0.5 ml/Kg of absolute ethanol is effective dose for complete renal infarction

Ethanol demand in Brazil: Regional approach

International Nuclear Information System (INIS)

Freitas, Luciano Charlita de; Kaneko, Shinji

2011-01-01

Successive studies attempting to clarify national aspects of ethanol demand have assisted policy makers and producers in defining strategies, but little information is available on the dynamic of regional ethanol markets. This study aims to analyze the characteristics of ethanol demand at the regional level taking into account the peculiarities of the developed center-south and the developing north-northeast regions. Regional ethanol demand is evaluated based on a set of market variables that include ethanol price, consumer's income, vehicle stock and prices of substitute fuels; i.e., gasoline and natural gas. A panel cointegration analysis with monthly observations from January 2003 to April 2010 is employed to estimate the long-run demand elasticity. The results reveal that the demand for ethanol in Brazil differs between regions. While in the center-south region the price elasticity for both ethanol and alternative fuels is high, consumption in the north-northeast is more sensitive to changes in the stock of the ethanol-powered fleet and income. These, among other evidences, suggest that the pattern of ethanol demand in the center-south region most closely resembles that in developed nations, while the pattern of demand in the north-northeast most closely resembles that in developing nations. - Research highlights: → Article consists of a first insight on regional demand for ethanol in Brazil. → It proposes a model with multiple fuels, i.e., hydrous ethanol, gasohol and natural gas. → Results evidence that figures for regional demand for ethanol differ amongst regions and with values reported for national demand. → Elasticities for the center-south keep similarities to patterns for fuel demand in developed nations while coefficients for the north-northeast are aligned to patterns on developing countries.

Ethanol demand in Brazil: Regional approach

Energy Technology Data Exchange (ETDEWEB)

Freitas, Luciano Charlita de, E-mail: lucianofreitas@hiroshima-u.ac.j [Graduate School for International Development and Cooperation, Development Policy, Hiroshima University 1-5-1 Kagamiyama, Higashi-Hiroshima, Hiroshima 739-8529 (Japan); Kaneko, Shinji [Graduate School for International Development and Cooperation, Development Policy, Hiroshima University 1-5-1 Kagamiyama, Higashi-Hiroshima, Hiroshima 739-8529 (Japan)

2011-05-15

Successive studies attempting to clarify national aspects of ethanol demand have assisted policy makers and producers in defining strategies, but little information is available on the dynamic of regional ethanol markets. This study aims to analyze the characteristics of ethanol demand at the regional level taking into account the peculiarities of the developed center-south and the developing north-northeast regions. Regional ethanol demand is evaluated based on a set of market variables that include ethanol price, consumer's income, vehicle stock and prices of substitute fuels; i.e., gasoline and natural gas. A panel cointegration analysis with monthly observations from January 2003 to April 2010 is employed to estimate the long-run demand elasticity. The results reveal that the demand for ethanol in Brazil differs between regions. While in the center-south region the price elasticity for both ethanol and alternative fuels is high, consumption in the north-northeast is more sensitive to changes in the stock of the ethanol-powered fleet and income. These, among other evidences, suggest that the pattern of ethanol demand in the center-south region most closely resembles that in developed nations, while the pattern of demand in the north-northeast most closely resembles that in developing nations. - Research highlights: {yields} Article consists of a first insight on regional demand for ethanol in Brazil. {yields} It proposes a model with multiple fuels, i.e., hydrous ethanol, gasohol and natural gas. {yields} Results evidence that figures for regional demand for ethanol differ amongst regions and with values reported for national demand. {yields} Elasticities for the center-south keep similarities to patterns for fuel demand in developed nations while coefficients for the north-northeast are aligned to patterns on developing countries.

Evaluation of cell proliferation, apoptosis, and dna-repair genes as potential biomarkers for ethanol-induced cns alterations

Directory of Open Access Journals (Sweden)

Hicks Steven D

2012-10-01

Full Text Available Abstract Background Alcohol use disorders (AUDs lead to alterations in central nervous system (CNS architecture along with impaired learning and memory. Previous work from our group and that of others suggests that one mechanism underlying these changes is alteration of cell proliferation, apoptosis, and DNA-repair in neural stem cells (NSCs produced as a consequence of ethanol-induced effects on the expression of genes related to p53-signaling. This study tests the hypothesis that changes in the expression of p53-signaling genes represent biomarkers of ethanol abuse which can be identified in the peripheral blood of rat drinking models and human AUD subjects and posits that specific changes may be correlated with differences in neuropsychological measures and CNS structure. Results Remarkably, microarray analysis of 350 genes related to p53-signaling in peripheral blood leukocytes (PBLs of binge-drinking rats revealed 190 genes that were significantly altered after correcting for multiple testing. Moreover, 40 of these genes overlapped with those that we had previously observed to be changed in ethanol-exposed mouse NSCs. Expression changes in nine of these genes were tested for independent confirmation by a custom QuantiGene Plex (QGP assay for a subset of p53-signaling genes, where a consistent trend for decreased expression of mitosis-related genes was observed. One mitosis-related gene (Pttg1 was also changed in human lymphoblasts cultured with ethanol. In PBLs of human AUD subjects seven p53-signaling genes were changed compared with non-drinking controls. Correlation and principal components analysis were then used to identify significant relationships between the expression of these seven genes and a set of medical, demographic, neuropsychological and neuroimaging measures that distinguished AUD and control subjects. Two genes (Ercc1 and Mcm5 showed a highly significant correlation with AUD-induced decreases in the volume of the left

Stereospecificity (ST) of the microsomal ethanol oxidizing system (MEOS)

International Nuclear Information System (INIS)

Alderman, J.; Kato, S.; Lasker, J.; Lieber, C.S.

1987-01-01

The ST of MEOS for the ethanol 1R hydrogen has been variously reported as absolute, partial or absent, with free radical involvement postulated in the latter case. To determine both the ST of MEOS and the participation of free radicals in the reaction, they investigated MEOS ST using 1R[1- 3 H] ethanol as substrate. ST is expressed as the fraction of 3 H labeling in acetaldehyde formed, relative to that in ethanol, and ranges from 0.5 to 0. Partial ST was observed using liver microsomes from both rats and hamsters; it significantly decreased after ethanol feeding. 0.1 mM desferrioxamine (dfx) did not increase ST in any of these microsomal preparations while ferric EDTA decreased it, suggesting that ethanol treatment induces a cytochrome P-450 with lower ST rather than increasing free radical involvement. This is supported by a virtual absence of ST observed in a reconstituted system containing purified hamster P-450/sub ALC/, a liver cytochrome P-450 isozyme induced in hamsters by ethanol treatment. Their results indicate that, unlike other enzymes that oxidize ethanol, MEOS has only partial ST. Thus, ST alone cannot be used as an index of free radical involvement but, when evaluated with the response of ST to dfx, it indicated that MEOS is unlikely to involve free radical attack on ethanol in solution

Ethanol- and trifluoroethanol-induced changes in phase states of DPPC membranes. Prodan emission-excitation fluorescence spectroscopy supported by PARAFAC analysis

Science.gov (United States)

Horochowska, Martyna; Cieślik-Boczula, Katarzyna; Rospenk, Maria

2018-03-01

It has been shown that Prodan emission-excitation fluorescence spectroscopy supported by Parallel Factor (PARAFAC) analysis is a fast, simple and sensitive method used in the study of the phase transition from the noninterdigitated gel (Lβ‧) state to the interdigitated gel (LβI) phase, triggered by ethanol and 2,2,2-trifluoroethanol (TFE) molecules in dipalmitoylphosphatidylcholines (DPPC) membranes. The relative contribution of lipid phases with spectral characteristics of each pure phase component has been presented as a function of an increase in alcohol concentration. It has been stated that both alcohol molecules can induce a formation of the LβI phase, but TFE is over six times stronger inducer of the interdigitated phase in DPPC membranes than ethanol molecules. Moreover, in the TFE-mixed DPPC membranes, the transition from the Lβ‧ to LβI phase is accompanied by a formation of the fluid phase, which most probably serves as a boundary phase between the Lβ‧ and LβI regions. Contrary to the three phase-state model of TFE-mixed DPPC membranes, in ethanol-mixed DPPC membranes only the two phase-state model has been detected.

Confocal laser scanning microscopy to estimate nanoparticles’ human skin penetration in vitro

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Zou Y

2017-10-01

Full Text Available Ying Zou,1,2,* Anna Celli,2,3,* Hanjiang Zhu,2,* Akram Elmahdy,2 Yachao Cao,2 Xiaoying Hui,2 Howard Maibach2 1Skin & Cosmetic Research Department, Shanghai Skin Disease Hospital, Shanghai, People’s Republic of China; 2Department of Dermatology, School of Medicine, University of California San Francisco, San Francisco, CA, USA; 3San Francisco Veterans Medical Center, San Francisco, CA, USA *These authors contributed equally to this work Objective: With rapid development of nanotechnology, there is increasing interest in nanoparticle (NP application and its safety and efficacy on human skin. In this study, we utilized confocal laser scanning microscopy to estimate NP skin penetration.Methods: Three different-sized polystyrene NPs marked with red fluorescence were applied to human skin, and Calcium Green 5N was used as a counterstain. Dimethyl sulfoxide (DMSO and ethanol were used as alternative vehicles for NPs. Tape stripping was utilized as a barrier-damaged skin model. Skin biopsies dosed with NPs were incubated at 4°C or 37°C for 24 hours and imaged using confocal laser scanning microscopy.Results: NPs were localized in the stratum corneum (SC and hair follicles without penetrating the epidermis/dermis. Barrier alteration with tape stripping and change in incubation temperature did not induce deeper penetration. DMSO enhanced NP SC penetration but ethanol did not.Conclusion: Except with DMSO vehicle, these hydrolyzed polystyrene NPs did not penetrate intact or barrier-damaged human “viable” epidermis. For further clinical relevance, in vivo human skin studies and more sensitive analytic chemical methodology are suggested. Keywords: nanoparticles, skin penetration, stratum corneum, confocal laser scanning microscopy, tape stripping

Quantification of high-power ultrasound induced damage on potato starch granules using light microscopy.

Science.gov (United States)

Zuo, Yue Yue J; Hébraud, Pascal; Hemar, Yacine; Ashokkumar, Muthupandian

2012-05-01

A simple light microscopic technique was developed in order to quantify the damage inflicted by high-power low-frequency ultrasound (0-160 W, 20 kHz) treatment on potato starch granules in aqueous dispersions. The surface properties of the starch granules were modified using ethanol and SDS washing methods, which are known to displace proteins and lipids from the surface of the starch granules. The study showed that in the case of normal and ethanol-washed potato starch dispersions, two linear regions were observed. The number of defects first increased linearly with an increase in ultrasound power up to a threshold level. This was then followed by another linear dependence of the number of defects on the ultrasound power. The power threshold where the change-over occurred was higher for the ethanol-washed potato dispersions compared to non-washed potato dispersions. In the case of SDS-washed potato starch, although the increase in defects was linear with the ultrasound power, the power threshold for a second linear region was not observed. These results are discussed in terms of the different possible mechanisms of cavitation induced-damage (hydrodynamic shear stresses and micro-jetting) and by taking into account the hydrophobicity of the starch granule surface. Copyright © 2011 Elsevier B.V. All rights reserved.

Highly stable and active Ni-doped ordered mesoporous carbon catalyst on the steam reforming of ethanol application

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Josh Y.Z. Chiou

2017-02-01

Full Text Available A novel one-step direct synthesis of nickel embedded in an ordered mesoporous carbon catalyst (NiOMC is done in a basic medium of nonaqueous solution by a solvent evaporation-induced self-assembly process. The NiOMC sample is characterized by a variety of analytical and spectroscopy techniques, e.g., N2 adsorption/desorption isotherm measurement, X-ray diffraction (XRD, transmission electron microscopy (TEM and temperature-programed reduction (TPR. In this study, the NiOMC catalyst is found to exhibit superior catalytic activity for the steam reforming of ethanol (SRE, showing high hydrogen selectivity and durability. Ethanol can be completely converted at 350 °C over the NiOMC catalyst. Also, the durability of the NiOMC catalyst on the SRE reaction exceeds 100 h at 450 °C, with SH2 approaching 65% and SCO of less than 1%.

The effects of continuous and intermittent ethanol exposure in adolesence on the aversive properties of ethanol during adulthood.

Science.gov (United States)

Diaz-Granados, Jaime L; Graham, Danielle L

2007-12-01

Alcohol abuse among adolescents is prevalent. Epidemiological studies suggest that alcohol abuse during the adolescent developmental period may result in long-term changes such as an increased susceptibility to alcohol-related problems in adulthood. Laboratory findings suggest that alcohol exposure during the adolescent developmental period, as compared with adulthood, may differentially impact subsequent neurobehavioral responses to alcohol. The present study was designed to examine whether ethanol exposure, continuous versus intermittent, during the adolescent developmental period would alter the aversive properties of ethanol in adult C3H mice. Periadolescent (PD28) male C3H mice were exposed to 64 hours of continuous or intermittent ethanol vapor. As a comparison, adult (PD70) C3H mice were also exposed to 64 hours of continuous or intermittent ethanol vapor. Six weeks after ethanol exposure, taste aversion conditioning was carried out on both ethanol pre-exposed and ethanol-naive animals using a 1-trial, 1-flavor taste-conditioning procedure. Ethanol exposure during the periadolescent period significantly attenuated a subsequent ethanol-induced conditioned taste aversion, as compared with control animals. Adult animals exposed to chronic ethanol vapor during adolescence showed less of an aversion to an ethanol-paired flavor than ethanol-naive adults. Intermittent exposure to ethanol vapor during periadolescence produced a greater attenuation. It is suggested that ethanol exposure during the periadolescent period results in long-term neurobehavioral changes, which lessen a conditioned aversion to ethanol in adulthood. It is suggested that this age-related effect may underlie the increased susceptibility to alcohol-related problems which is negatively correlated with the age of onset for alcohol abuse.

Preparation and characterization of micro-arc-induced Pd/TM(TM = Ni, Co and Ti) catalysts and comparison of their electrocatalytic activities toward ethanol oxidation

International Nuclear Information System (INIS)

Wang, Xiaoguang; Ma, Guanshui; Zhu, Fuchun; Lin, Naiming; Tang, Bin; Zhang, Zhonghua

2013-01-01

Using the electro-spark deposition technique, a novel kind of Pd/TM (TM = Ni, Co and Ti) electrode was successfully prepared by arc-depositing Pd on the transition metal substrates. The structure, morphology and chemical composition of the arc-deposited films were investigated using thin-film X-ray diffraction (TF-XRD), scanning electron microscopy (SEM) and energy dispersive X-ray analysis (EDX). The results show that, a coarsening topographical morphology can be obtained, being composed of numerous craters/spots with sizes ranging from nano-scales to several microns. The electrochemical measurements indicate that the arc-deposited Pd/TM electrodes exhibit distinct electrochemical behaviors and the catalytic activity toward ethanol electro-oxidation reaction (EOR) is highly dependent upon the nature of substrate. Among the Pd/TM electrodes investigated, the arc-deposited Pd/Co reveals the best activity and superior poisoning tolerance towards ethanol oxidation and will find promising applications as a candidate for the anode catalyst of direct ethanol fuel cells (DEFCs)

Chronic intermittent ethanol exposure during adolescence: effects on social behavior and ethanol sensitivity in adulthood.

Science.gov (United States)

Varlinskaya, Elena I; Truxell, Eric; Spear, Linda P

2014-08-01

This study assessed long-lasting consequences of repeated ethanol exposure during two different periods of adolescence on 1) baseline levels of social investigation, play fighting, and social preference and 2) sensitivity to the social consequences of acute ethanol challenge. Adult male and female Sprague-Dawley rats were tested 25 days after repeated exposure to ethanol (3.5 g/kg intragastrically [i.g.], every other day for a total of 11 exposures) in a modified social interaction test. Early-mid adolescent intermittent exposure (e-AIE) occurred between postnatal days (P) 25 and 45, whereas late adolescent intermittent exposure (l-AIE) was conducted between P45 and P65. Significant decreases in social investigation and social preference were evident in adult male rats, but not their female counterparts following e-AIE, whereas neither males nor females demonstrated these alterations following l-AIE. In contrast, both e-AIE and l-AIE produced alterations in sensitivity to acute ethanol challenge in males tested 25 days after adolescent exposure. Ethanol-induced facilitation of social investigation and play fighting, reminiscent of that normally seen during adolescence, was evident in adult males after e-AIE, whereas control males showed an age-typical inhibition of social behavior. Males after l-AIE were found to be insensitive to the socially suppressing effects of acute ethanol challenge, suggesting the development of chronic tolerance in these animals. In contrast, females showed little evidence for alterations in sensitivity to acute ethanol challenge following either early or late AIE. The results of the present study demonstrate a particular vulnerability of young adolescent males to long-lasting detrimental effects of repeated ethanol. Retention of adolescent-typical sensitivity to the socially facilitating effects of ethanol could potentially make ethanol especially appealing to these males, therefore promoting relatively high levels of ethanol intake later

Can nerve regeneration on an artificial nerve conduit be enhanced by ethanol-induced cervical sympathetic ganglion block?

Directory of Open Access Journals (Sweden)

Yoshiki Shionoya

Full Text Available This study aimed to determine whether nerve regeneration by means of an artificial nerve conduit is promoted by ethanol-induced cervical sympathetic ganglion block (CSGB in a canine model. This study involved two experiments-in part I, the authors examined the effect of CSGB by ethanol injection on long-term blood flow to the orofacial region; part II involved evaluation of the effect of CSGB by ethanol injection on inferior alveolar nerve (IAN repair using polyglycolic acid-collagen tubes. In part I, seven Beagles were administered left CSGB by injection of 99.5% ethanol under direct visualization by means of thoracotomy, and changes in oral mucosal blood flow in the mental region and nasal skin temperature were evaluated. The increase in blood flow on the left side lasted for 7 weeks, while the increase in average skin temperature lasted 10 weeks on the left side and 3 weeks on the right. In part II, fourteen Beagles were each implanted with a polyglycolic acid-collagen tube across a 10-mm gap in the left IAN. A week after surgery, seven of these dogs were administered CSGB by injection of ethanol. Electrophysiological findings at 3 months after surgery revealed significantly higher sensory nerve conduction velocity and recovery index (ratio of left and right IAN peak amplitudes after nerve regeneration in the reconstruction+CSGB group than in the reconstruction-only group. Myelinated axons in the reconstruction+CSGB group were greater in diameter than those in the reconstruction-only group. Administration of CSGB with ethanol resulted in improved nerve regeneration in some IAN defects. However, CSGB has several physiological effects, one of which could possibly be the long-term increase in adjacent blood flow.

Can nerve regeneration on an artificial nerve conduit be enhanced by ethanol-induced cervical sympathetic ganglion block?

Science.gov (United States)

Sunada, Katsuhisa; Shigeno, Keiji; Nakada, Akira; Honda, Michitaka; Nakamura, Tatsuo

2017-01-01

This study aimed to determine whether nerve regeneration by means of an artificial nerve conduit is promoted by ethanol-induced cervical sympathetic ganglion block (CSGB) in a canine model. This study involved two experiments—in part I, the authors examined the effect of CSGB by ethanol injection on long-term blood flow to the orofacial region; part II involved evaluation of the effect of CSGB by ethanol injection on inferior alveolar nerve (IAN) repair using polyglycolic acid-collagen tubes. In part I, seven Beagles were administered left CSGB by injection of 99.5% ethanol under direct visualization by means of thoracotomy, and changes in oral mucosal blood flow in the mental region and nasal skin temperature were evaluated. The increase in blood flow on the left side lasted for 7 weeks, while the increase in average skin temperature lasted 10 weeks on the left side and 3 weeks on the right. In part II, fourteen Beagles were each implanted with a polyglycolic acid-collagen tube across a 10-mm gap in the left IAN. A week after surgery, seven of these dogs were administered CSGB by injection of ethanol. Electrophysiological findings at 3 months after surgery revealed significantly higher sensory nerve conduction velocity and recovery index (ratio of left and right IAN peak amplitudes) after nerve regeneration in the reconstruction+CSGB group than in the reconstruction-only group. Myelinated axons in the reconstruction+CSGB group were greater in diameter than those in the reconstruction-only group. Administration of CSGB with ethanol resulted in improved nerve regeneration in some IAN defects. However, CSGB has several physiological effects, one of which could possibly be the long-term increase in adjacent blood flow. PMID:29220373

Ethanol metabolism, oxidative stress, and endoplasmic reticulum stress responses in the lungs of hepatic alcohol dehydrogenase deficient deer mice after chronic ethanol feeding

Energy Technology Data Exchange (ETDEWEB)

Kaphalia, Lata [Department of Internal Medicine, The University of Texas Medical Branch, Galveston, TX 775555 (United States); Boroumand, Nahal [Department of Pathology, The University of Texas Medical Branch, Galveston, TX 775555 (United States); Hyunsu, Ju [Department of Preventive Medicine and Community Health, The University of Texas Medical Branch, Galveston, TX 775555 (United States); Kaphalia, Bhupendra S., E-mail: bkaphali@utmb.edu [Department of Pathology, The University of Texas Medical Branch, Galveston, TX 775555 (United States); Calhoun, William J. [Department of Internal Medicine, The University of Texas Medical Branch, Galveston, TX 775555 (United States)

2014-06-01

Consumption and over-consumption of alcoholic beverages are well-recognized contributors to a variety of pulmonary disorders, even in the absence of intoxication. The mechanisms by which alcohol (ethanol) may produce disease include oxidative stress and prolonged endoplasmic reticulum (ER) stress. Many aspects of these processes remain incompletely understood due to a lack of a suitable animal model. Chronic alcohol over-consumption reduces hepatic alcohol dehydrogenase (ADH), the principal canonical metabolic pathway of ethanol oxidation. We therefore modeled this situation using hepatic ADH-deficient deer mice fed 3.5% ethanol daily for 3 months. Blood ethanol concentration was 180 mg% in ethanol fed mice, compared to < 1.0% in the controls. Acetaldehyde (oxidative metabolite of ethanol) was minimally, but significantly increased in ethanol-fed vs. pair-fed control mice. Total fatty acid ethyl esters (FAEEs, nonoxidative metabolites of ethanol) were 47.6 μg/g in the lungs of ethanol-fed mice as compared to 1.5 μg/g in pair-fed controls. Histological and immunohistological evaluation showed perivascular and peribronchiolar lymphocytic infiltration, and significant oxidative injury, in the lungs of ethanol-fed mice compared to pair-fed controls. Several fold increases for cytochrome P450 2E1, caspase 8 and caspase 3 found in the lungs of ethanol-fed mice as compared to pair-fed controls suggest role of oxidative stress in ethanol-induced lung injury. ER stress and unfolded protein response signaling were also significantly increased in the lungs of ethanol-fed mice. Surprisingly, no significant activation of inositol-requiring enzyme-1α and spliced XBP1 was observed indicating a lack of activation of corrective mechanisms to reinstate ER homeostasis. The data suggest that oxidative stress and prolonged ER stress, coupled with formation and accumulation of cytotoxic FAEEs may contribute to the pathogenesis of alcoholic lung disease. - Highlights: • Chronic

Ethanol metabolism, oxidative stress, and endoplasmic reticulum stress responses in the lungs of hepatic alcohol dehydrogenase deficient deer mice after chronic ethanol feeding

International Nuclear Information System (INIS)

Kaphalia, Lata; Boroumand, Nahal; Hyunsu, Ju; Kaphalia, Bhupendra S.; Calhoun, William J.

2014-01-01

Consumption and over-consumption of alcoholic beverages are well-recognized contributors to a variety of pulmonary disorders, even in the absence of intoxication. The mechanisms by which alcohol (ethanol) may produce disease include oxidative stress and prolonged endoplasmic reticulum (ER) stress. Many aspects of these processes remain incompletely understood due to a lack of a suitable animal model. Chronic alcohol over-consumption reduces hepatic alcohol dehydrogenase (ADH), the principal canonical metabolic pathway of ethanol oxidation. We therefore modeled this situation using hepatic ADH-deficient deer mice fed 3.5% ethanol daily for 3 months. Blood ethanol concentration was 180 mg% in ethanol fed mice, compared to < 1.0% in the controls. Acetaldehyde (oxidative metabolite of ethanol) was minimally, but significantly increased in ethanol-fed vs. pair-fed control mice. Total fatty acid ethyl esters (FAEEs, nonoxidative metabolites of ethanol) were 47.6 μg/g in the lungs of ethanol-fed mice as compared to 1.5 μg/g in pair-fed controls. Histological and immunohistological evaluation showed perivascular and peribronchiolar lymphocytic infiltration, and significant oxidative injury, in the lungs of ethanol-fed mice compared to pair-fed controls. Several fold increases for cytochrome P450 2E1, caspase 8 and caspase 3 found in the lungs of ethanol-fed mice as compared to pair-fed controls suggest role of oxidative stress in ethanol-induced lung injury. ER stress and unfolded protein response signaling were also significantly increased in the lungs of ethanol-fed mice. Surprisingly, no significant activation of inositol-requiring enzyme-1α and spliced XBP1 was observed indicating a lack of activation of corrective mechanisms to reinstate ER homeostasis. The data suggest that oxidative stress and prolonged ER stress, coupled with formation and accumulation of cytotoxic FAEEs may contribute to the pathogenesis of alcoholic lung disease. - Highlights: • Chronic

Percutaneous Ethanol Injection via an Artificially Induced Right Hydrothorax for Hepatocellular Carcinoma in the Hepatic Dome

International Nuclear Information System (INIS)

Kume, Akimichi; Nimura, Yuji; Kamiya, Junichi; Nagino, Masato; Kito, Yasushi

2003-01-01

To evaluate the efficacy of sonographically (US) guided percutaneous ethanol injection (PEI) via an artificially induced right hydrothorax (transthoracic PEI) to treat US-invisible hepatocellular carcinoma (HCC) in the hepatic dome. Five cirrhotic patients with US-invisible HCC in the hepatic dome, who were poor surgical candidates, underwent transthoracic PEI. An artificial right hydrothorax was created by instilling 500 ml saline, and absolute ethanol was injected transhydrothoracically into the hepatic dome lesion under local anesthesia. The success and complications were assessed radiologically. The patients were followed up serologically and radiologically for 12-44 (mean 28.4) months. Twenty-five hydrothoraces were induced. All hydrothoraces enabled US visualization of the entire hepatic dome. Eight of the nine small lesions were treated successfully by the treatment. Two of the three local recurrences were eradicated by repeat transthoracic PEI. One large lesion was treated by a combination of transthoracic and regular PEI. The only complication was one clinically insignificant pneumothorax. Induction of a right hydrothorax is feasible and safe. The hydrothorax enables US visualization of the entire hepatic dome and permits US-guided PEI for HCC in the hepatic dome that otherwise would not be possible

Predictors of ethanol consumption in adult Sprague-Dawley rats: relation to hypothalamic peptides that stimulate ethanol intake.

Science.gov (United States)

Karatayev, Olga; Barson, Jessica R; Carr, Ambrose J; Baylan, Jessica; Chen, Yu-Wei; Leibowitz, Sarah F

2010-06-01

To investigate mechanisms in outbred animals that increase the propensity to consume ethanol, it is important to identify and characterize these animals before or at early stages in their exposure to ethanol. In the present study, different measures were examined in adult Sprague-Dawley rats to determine whether they can predict long-term propensity to overconsume ethanol. Before consuming 9% ethanol with a two-bottle choice paradigm, rats were examined with the commonly used behavioral measures of novelty-induced locomotor activity and anxiety, as assessed during 15 min in an open-field activity chamber. Two additional measures, intake of a low 2% ethanol concentration or circulating triglyceride (TG) levels after a meal, were also examined with respect to their ability to predict chronic 9% ethanol consumption. The results revealed significant positive correlations across individual rats between the amount of 9% ethanol ultimately consumed and three of these different measures, with high scores for activity, 2% ethanol intake, and TGs identifying rats that consume 150% more ethanol than rats with low scores. Measurements of hypothalamic peptides that stimulate ethanol intake suggest that they contribute early to the greater ethanol consumption predicted by these high scores. Rats with high 2% ethanol intake or high TGs, two measures found to be closely related, had significantly elevated expression of enkephalin (ENK) and galanin (GAL) in the hypothalamic paraventricular nucleus (PVN) but no change in neuropeptide Y (NPY) in the arcuate nucleus (ARC). This is in contrast to rats with high activity scores, which in addition to elevated PVN ENK expression showed enhanced NPY in the ARC but no change in GAL. Elevated ENK is a common characteristic related to all three predictors of chronic ethanol intake, whereas the other peptides differentiate these predictors, with GAL enhanced with high 2% ethanol intake and TG measures but NPY related to activity. 2010 Elsevier

A mouse model of prenatal ethanol exposure using a voluntary drinking paradigm.

Science.gov (United States)

Allan, Andrea M; Chynoweth, Julie; Tyler, Lani A; Caldwell, Kevin K

2003-12-01

The incidence of fetal alcohol spectrum disorders is estimated to be as high as 1 in 100 births. Efforts to better understand the basis of prenatal ethanol-induced impairments in brain functioning, and the mechanisms by which ethanol produces these defects, will rely on the use of animal models of fetal alcohol exposure (FAE). Using a saccharin-sweetened alcohol solution, we developed a free-choice, moderate alcohol access model of prenatal alcohol exposure. Stable drinking of a saccharin solution (0.066%) was established in female mice. Ethanol then was added to the saccharin in increasing concentrations (2%, 5%, 10% w/v) every 2 days. Water was always available, and mice consumed standard pellet chow. Control mice drank saccharin solution without ethanol. After a stable baseline of ethanol consumption (14 g/kg/day) was obtained, females were impregnated. Ethanol consumption continued throughout pregnancy and then was decreased to 0% in a step-wise fashion over a period of 6 days after pups were delivered. Characterization of the model included measurements of maternal drinking patterns, blood alcohol levels, food consumption, litter size, pup weight, pup retrieval times for the dams, and effects of FAE on performance in fear-conditioned learning and novelty exploration. Maternal food consumption, maternal care, and litter size and number were all found to be similar for the alcohol-exposed and saccharin control animals. FAE did not alter locomotor activity in an open field but did increase the time spent inspecting a novel object introduced into the open field. FAE mice displayed reduced contextual fear when trained using a delay fear conditioning procedure. The mouse model should be a useful tool in testing hypotheses about the neural mechanisms underlying the learning deficits present in fetal alcohol spectrum disorders. Moreover, a mouse prenatal ethanol model should increase the opportunity to use the power of genetically defined and genetically altered mouse

Phenolic Compounds Protect Cultured Hippocampal Neurons against Ethanol-Withdrawal Induced Oxidative Stress

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Marianna E. Jung

2009-04-01

Full Text Available Ethanol withdrawal is linked to elevated oxidative damage to neurons. Here we report our findings on the contribution of phenolic antioxidants (17β-estradiol, p-octyl-phenol and 2,6-di-tert-butyl-4-methylphenol to counterbalance sudden ethanol withdrawal-initiated oxidative events in hippocampus-derived cultured HT-22 cells. We showed that ethanol withdrawal for 4 h after 24-h ethanol treatment provoked greater levels of oxidative damage than the preceding ethanol exposure. Phenolic antioxidant treatment either during ethanol exposure or ethanol withdrawal only, however, dose-dependently reversed cellular oxidative damage, as demonstrated by the significantly enhanced cell viability, reduced malondialdehyde production and protein carbonylation, compared to untreated cells. Interestingly, the antioxidant treatment schedule had no significant impact on the observed neuroprotection. In addition, the efficacy of the three phenolic compounds was practically equipotent in protecting HT-22 cells in spite of predictions based on an in silico study and a cell free assay of lipid peroxidation. This finding implies that free-radical scavenging may not be the sole factor responsible for the observed neuroprotection and warrants further studies to establish, whether the HT-22 line is indeed a suitable model for in vitro screening of antioxidants against EW-related neuronal damage.

The time course of ethanol tolerance: associative learning

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J.L.O. Bueno

2007-11-01

Full Text Available The effect of different contextual stimuli on different ethanol-induced internal states was investigated during the time course of both the hypothermic effect of the drug and of drug tolerance. Minimitters were surgically implanted in 16 Wistar rats to assess changes in their body temperature under the effect of ethanol. Rat groups were submitted to ethanol or saline trials every other day. The animals were divided into two groups, one receiving a constant dose (CD of ethanol injected intraperitoneally, and the other receiving increasing doses (ID during the 10 training sessions. During the ethanol training sessions, conditioned stimuli A (tone and B (buzzer were presented at "state +" (35 min after drug injection and "state -" (170 min after drug injection, respectively. Conditioned stimuli C (bip and D (white noise were presented at moments equivalent to stimuli A and B, respectively, but during the saline training sessions. All stimuli lasted 15 min. The CD group, but not the ID group, developed tolerance to the hypothermic effect of ethanol. Stimulus A (associated with drug "state +" induced hyperthermia with saline injection in the ID group. Stimulus B (associated with drug "state -" reduced ethanol tolerance in the CD group and modulated the hypothermic effect of the drug in the ID group. These results indicate that contextual stimuli acquire modulatory conditioned properties that are associated with the time course of both the action of the drug and the development of drug tolerance.

Effect of Ipomoea aquatica ethanolic extract in streptozotocin (STZ) induced diabetic rats via1H NMR-based metabolomics approach.

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Abu Bakar Sajak, Azliana; Mediani, Ahmed; Maulidiani; Mohd Dom, Nur Sumirah; Machap, Chandradevan; Hamid, Muhajir; Ismail, Amin; Khatib, Alfi; Abas, Faridah

2017-12-01

Ipomoea aquatica (locally known as "kangkung") has previously been reported to have hypoglycemic activities on glucose level in diabetes patients. However, the effect of I. aquatica ethanolic extract on the metabolites in the body has remained unknown. This study provides new insights on the changes of endogenous metabolites caused by I. aquatica ethanolic extract and improves the understanding on the therapeutic efficacy and mechanism of I. aquatica ethanolic extract. By using a combination of 1 H nuclear magnetic resonance (NMR) with multivariate analysis (MVDA), the changes of metabolites due to I. aquatica ethanolic extract administration in obese diabetic-induced Sprague Dawley rats (OB+STZ+IA) were identified. The results suggested 19 potential biomarkers with variable importance projections (VIP) above 0.5, which include creatine/creatinine, glucose, creatinine, citrate, carnitine, 2-oxoglutarate, succinate, hippurate, leucine, 1-methylnicotinamice (MNA), taurine, 3-hydroxybutyrate (3-HB), tryptophan, lysine, trigonelline, allantoin, formiate, acetoacetate (AcAc) and dimethylamine. From the changes in the metabolites, the affected pathways and aspects of metabolism were identified. I. aquatica ethanolic extract increases metabolite levels such as creatinine/creatine, carnitine, MNA, trigonelline, leucine, lysine, 3-HB and decreases metabolite levels, including glucose and tricarboxylic acid (TCA) intermediates. This implies capabilities of I. aquatica ethanolic extract promoting glycolysis, gut microbiota and nicotinate/nicotinamide metabolism, improving the glomerular filtration rate (GFR) and reducing the β-oxidation rate. However, the administration of I. aquatica ethanolic extract has several drawbacks, such as unimproved changes in amino acid metabolism, especially in reducing branched chain amino acid (BCAA) synthesis pathways and lipid metabolism. Copyright © 2017 Elsevier GmbH. All rights reserved.

Femtosecond laser fluence based nanostructuring of W and Mo in ethanol

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Bashir, Shazia; Rafique, Muhammad Shahid; Nathala, Chandra Sekher; Ajami, Ali Asghar; Husinsky, Wolfgang

2017-05-01

The effect of femtosecond laser fluence on nanostructuring of Tungsten (W) and Molybdenum (Mo) has been investigated after ablation in ethanol environment. A Ti: Sapphire laser (800 nm, 30 fs) at fluences ranging from 0.6 to 5.7 J cm-2 was employed to ablate targets. The growth of structures on the surface of irradiated targets is investigated by Field Emission Scanning Electron Microscope (FESEM) analysis. The SEM was performed for both central as well as the peripheral ablated regions. It is observed that both the development and shape of nanoscale features is dependent upon deposited energies to the target surface as well as nature of material. Nanostructures grown on Mo are more distinct and well defined as compared to W. At central ablated areas of W, unorganized Laser Induced Periodic Surface Structures (LIPSS) are grown at low fluences, whereas, nonuniform melting along with cracking is observed at higher fluences. In case of Mo, well-defined and organized LIPSS are observed for low fluences. With increasing fluence, LIPSS become unorganized and broken with an appearance of cracks and are completely vanished with the formation of nanoscale cavities and conical structures. In case of peripheral ablated areas broken and bifurcated LIPSS are grown for all fluences for both materials. The, ablated diameter, ablation depth, ablation rate and the dependence of periodicity of LIPSS on the laser fluence are also estimated for both W and Mo. Parametric instabilities of laser-induced plasma along with generation and scattering of surface plasmons is considered as a possible cause for the formation of LIPSS. For ethanol assisted ablation, the role of bubble cavitation, precipitation, confinement and the convective flow is considered to be responsible for inducing increased hydrodynamic instabilities at the liquid-solid interface.

Femtosecond laser fluence based nanostructuring of W and Mo in ethanol

Energy Technology Data Exchange (ETDEWEB)

Bashir, Shazia, E-mail: shaziabashir@gcu.edu.pk [Institute of Applied Physics, Vienna University of Technology, Vienna (Austria); Centre for Advanced Studies in Physics, Government College University Lahore (Pakistan); Rafique, Muhammad Shahid [Institute of Applied Physics, Vienna University of Technology, Vienna (Austria); Department of Physics, University of Engineering and Technology Lahore (Pakistan); Nathala, Chandra Sekher [Institute of Applied Physics, Vienna University of Technology, Vienna (Austria); Ajami, Ali Asghar [Institute of Applied Physics, Vienna University of Technology, Vienna (Austria); Faculty of Physics, Semnan University, Semnan (Iran, Islamic Republic of); Husinsky, Wolfgang [Institute of Applied Physics, Vienna University of Technology, Vienna (Austria)

2017-05-15

The effect of femtosecond laser fluence on nanostructuring of Tungsten (W) and Molybdenum (Mo) has been investigated after ablation in ethanol environment. A Ti: Sapphire laser (800 nm, 30 fs) at fluences ranging from 0.6 to 5.7 J cm{sup −2} was employed to ablate targets. The growth of structures on the surface of irradiated targets is investigated by Field Emission Scanning Electron Microscope (FESEM) analysis. The SEM was performed for both central as well as the peripheral ablated regions. It is observed that both the development and shape of nanoscale features is dependent upon deposited energies to the target surface as well as nature of material. Nanostructures grown on Mo are more distinct and well defined as compared to W. At central ablated areas of W, unorganized Laser Induced Periodic Surface Structures (LIPSS) are grown at low fluences, whereas, nonuniform melting along with cracking is observed at higher fluences. In case of Mo, well-defined and organized LIPSS are observed for low fluences. With increasing fluence, LIPSS become unorganized and broken with an appearance of cracks and are completely vanished with the formation of nanoscale cavities and conical structures. In case of peripheral ablated areas broken and bifurcated LIPSS are grown for all fluences for both materials. The, ablated diameter, ablation depth, ablation rate and the dependence of periodicity of LIPSS on the laser fluence are also estimated for both W and Mo. Parametric instabilities of laser-induced plasma along with generation and scattering of surface plasmons is considered as a possible cause for the formation of LIPSS. For ethanol assisted ablation, the role of bubble cavitation, precipitation, confinement and the convective flow is considered to be responsible for inducing increased hydrodynamic instabilities at the liquid-solid interface.

Weak-beam electron microscopy of radiation-induced segregation

International Nuclear Information System (INIS)

Saka, H.

1983-01-01

The segregation of solute atoms to dislocations during irradiation by 1 MeV electrons in a HVEM was studied by measuring the dissociation width of extended dislocations in Cu-5.1 at.%Si, Cu-5.3 at.%Ge, Ag-9.4 at.% In and Ag-9.6 at.%Al alloys. 'Weak-beam' electron microscopy was used. In Cu-Si (oversized solute), Cu-Ge (oversize) and Ag-Al (undersize), solute enrichment was observed near dislocations, while in Ag-In (oversize) solute depletion was observed. The results are discussed in terms of current mechanisms for radiation-induced segregation. (author)

Hippocampal nicotinic receptors have a modulatory role for ethanol and MDMA interaction in memory retrieval.

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Rostami, Maryam; Rezayof, Ameneh; Alijanpour, Sakineh; Sharifi, Khadijeh Alsadat

2017-08-15

The aim of the current study was to examine the effect of dorsal hippocampal nicotinic acetylcholine receptors (nAChRs) activation on the functional interaction between ethanol and 3,4-methylenedioxy-N-methylamphetamine (MDMA or ecstasy) in memory retrieval. The dorsal hippocampal CA1 regions of adult male NMRI mice were bilaterally cannulated and memory retrieval was measured in a step-down type passive avoidance apparatus. Post-training or pre-test systemic administration of ethanol (1g/kg, i.p.) induced amnesia. Pre-test administration of ethanol reversed pre-training ethanol-induced amnesia, suggesting ethanol state-dependent learning. Pre-test intra-CA1 microinjection of different doses of MDMA (0.25-1µg/mouse) with an ineffective dose of ethanol (0.25g/kg, i.p.) also induced amnesia. Interestingly, pre-test intra-CA1 microinjection of MDMA (0.25-1µg/mouse) potentiated ethanol state-dependent learning. On the other hand, the activation of the dorsal hippocampal nAChRs by pre-test microinjection of nicotine (0.1-1µg/mouse, intra-CA1) improved amnesia induced by the co-administration of MDMD and ethanol. It is important to note that intra-CA1 microinjection of the same doses of MDMA or nicotine could not affect memory formation by itself. Pre-test intra-CA1 microinjection of nicotine (0.3-0.9µg/mouse) could not reverse amnesia induced by pre-training administration of ethanol while this treatment enhanced MDMA response on ethanol state-dependent learning. Thus, it can be concluded that there may be functional interactions among ethanol, MDMA and nicotine via the dorsal hippocampal nicotinic acetylcholine receptor mechanism in memory retrieval and drug state-dependent learning. Copyright © 2017 Elsevier B.V. All rights reserved.

SELECTIVE VULNERABILITY OF EMBRYONIC CELL POPULATIONS TO ETHANOL-INDUCED APOPTOSIS: IMPLICATIONS FOR ALCOHOL RELATED BIRTH DEFECTS AND NEURODEVELOPMENTAL DISORDER

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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...

Ethanol stimulates ROS generation by mitochondria through Ca2+ mobilization and increases GFAP content in rat hippocampal astrocytes.

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González, Antonio; Pariente, José A; Salido, Ginés M

2007-10-31

We have employed rat hippocampal astrocytes in culture to investigate the effect of ethanol on reactive oxygen species (ROS) production as well as its effect on [Ca2+]c and GFAP expression. Cells were loaded with the fluorescent probes fura-2 and H2DCFDA for the determination of changes in [Ca2+]c and ROS production respectively, employing spectrofluorimetry. GFAP content was determined by immunocytochemistry and confocal scanning microscopy. Our results show ROS production in response to 50 mM ethanol, that was reduced in Ca2+-free medium (containing 0.5 mM EGTA) and in the presence of the intracellular Ca2+ chelator BAPTA (10 microM). The effect of ethanol on ROS production was significantly reduced in the presence of the alcohol dehydrogenase inhibitor 4-methylpyrazole (1 mM), and the antioxidants resveratrol (100 microM) or catalase (300 U/ml). Preincubation of astrocytes in the presence of 10 microM antimycin plus 10 microM oligomycin to inhibit mitochondria completely blocked ethanol-evoked ROS production. In addition, ethanol led to a sustained increase in [Ca2+]c that reached a constant level over the prestimulation values. Finally, incubation of astrocytes in the presence of ethanol increased the content of GFAP that was significantly reduced in the absence of extracellular Ca2+ and by resveratrol and catalase pretreatment. The data obtained in the present study suggest that astrocytes are able to metabolize ethanol, which induces two effects on intracellular homeostasis: an immediate response (Ca2+ release and ROS generation) and later changes involving GFAP expression. Both effects may underline various signaling pathways which are important for cell proliferation, differentiation and function.

Drinking typography established by scheduled induction predicts chronic heavy drinking in a monkey model of ethanol self-administration.

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Grant, Kathleen A; Leng, Xiaoyan; Green, Heather L; Szeliga, Kendall T; Rogers, Laura S M; Gonzales, Steven W

2008-10-01

We have developed an animal model of alcohol self-administration that initially employs schedule-induced polydipsia (SIP) to establish reliable ethanol consumption under open access (22 h/d) conditions with food and water concurrently available. SIP is an adjunctive behavior that is generated by constraining access to an important commodity (e.g., flavored food). The induction schedule and ethanol polydipsia generated under these conditions affords the opportunity to investigate the development of drinking typologies that lead to chronic, excessive alcohol consumption. Adult male cynomolgus monkeys (Macaca fascicularis) were induced to drink water and 4% (w/v in water) ethanol by a Fixed-Time 300 seconds (FT-300 seconds) schedule of banana-flavored pellet delivery. The FT-300 seconds schedule was in effect for 120 consecutive sessions, with daily induction doses increasing from 0.0 to 0.5 g/kg to 1.0 g/kg to 1.5 g/kg every 30 days. Following induction, the monkeys were allowed concurrent access to 4% (w/v) ethanol and water for 22 h/day for 12 months. Drinking typographies during the induction of drinking 1.5 g/kg ethanol emerged that were highly predictive of the daily ethanol intake over the next 12 months. Specifically, the frequency in which monkeys ingested 1.5 g/kg ethanol without a 5-minute lapse in drinking (defined as a bout of drinking) during induction strongly predicted (correlation 0.91) subsequent ethanol intake over the next 12 months of open access to ethanol. Blood ethanol during induction were highly correlated with intake and with drinking typography and ranged from 100 to 160 mg% when the monkeys drank their 1.5 g/kg dose in a single bout. Forty percent of the population became heavy drinkers (mean daily intakes >3.0 g/kg for 12 months) characterized by frequent "spree" drinking (intakes >4.0 g/kg/d). This model of ethanol self-administration identifies early alcohol drinking typographies (gulping the equivalent of 6 drinks) that evolve into

Protective effect of Opuntia ficus indica f. inermis prickly pear juice upon ethanol-induced damages in rat erythrocytes.

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Alimi, Hichem; Hfaeidh, Najla; Bouoni, Zouhour; Sakly, Mohsen; Ben Rhouma, Khémais

2012-05-01

Juice from the fruit of the cactus Opuntia ficus indica is claimed to possess several health-beneficial properties. The present study was carried out to determine whether O. ficus indica f. inermis fruit extract might have a protective effect upon physiological and morphological damages inflicted to erythrocytes membrane by chronic ethanol poisoning, per os, in rat. Chemical analysis of the extract revealed the presence of polyphenols, flavonoids, ascorbic acid, carotenoids, and betalains. Ethanol administration (3 g/kg b.w, per day for 90 days) induced an increase of malondialdehyde (MDA) and carbonylated proteins levels and a decrease of glutathione (GSH) level in erythrocyte. Ethanol administration also reduced the scavenging activity in plasma and enhanced erythrocytes hemolysis, as compared to control rats. In addition, ethanol intake increased the erythrocyte shape index by +895.5% and decreased the erythrocyte diameter by -61.53% as compared to controls. In animals also given prickly pear juice during the same experimental period, the studied parameters were much less shifted. This protective effect was found to be dose-dependent. It is likely that the beneficial effect of the extract is due to the high content of antioxidant compounds. Copyright © 2012 Elsevier Inc. All rights reserved.

Increased hepatic FAT/CD36, PTP1B and decreased HNF4A expression contributes to dyslipidemia associated with ethanol-induced liver dysfunction: Rescue effect of ginger extract.

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Shirpoor, Alireza; Heshmati, Elaheh; Kheradmand, Fatemeh; Gharalari, Farzaneh Hosseini; Chodari, Leila; Naderi, Roya; Majd, Farideh Nezami; Samadi, Mahrokh

2018-05-28

The association between chronic alcohol consumption and the development of alcpholic liver disease is a very well known phenomenon, but the precise underlying molecular mediators involved in ethanol-induced liver disease remain elusive. This study aimed to characterize the lipid metabolism alterations and the molecular mediators which are related to lipid metabolism in liver under the heavy ethanol exposure alone or combined with ginger extract. Twenty-four male wistar rats were assigned into three groups, namely control, ethanol, and ginger extract treated ethanol (GETE) groups. Six weeks after the treatment, the ethanol group showed a significant increase in fatty acid translocase (FAT)/CD36, protein tyrosine phosphatase 1B (PTP1B) and decrease hepatocyte nuclear factor 4 Alpha (HNF4A) genes expressions compared to the control group. The ethanol administration also significantly increased plasma LDL, cholesterol, triglyceride, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) compared to the control group. Moreover, compared to the control group, the ethanol group showed liver histhological changes, such as fibrosis, focal microvesicular steatosis, some apoptotic hepatocytes, spotty necrosis, portal lymphocytic inflammation, mallory-denk bodies, giant mitochondria, piecemeal necrosis. Consumption of ginger extract along with ethanol, partially ameliorated gene expression alteration and histological changes, improved undesirable lipid profile and liver enzymes changes compare to those in the ethanol group. These findings indicate that ethanol-induced liver abnormalities may in part be associated with lipid homeostasis changes mediated by overexpression of FAT/CD36, PTP1B and downexpressionof HNF4A genes. It also show that these effects can be reduced by using ginger extract as an antioxidant and anti-inflammatory agent. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Neuronal basis of innate olfactory attraction to ethanol in Drosophila.

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Andrea Schneider

Full Text Available The decision to move towards a mating partner or a food source is essential for life. The mechanisms underlying these behaviors are not well understood. Here, we investigated the role of octopamine - the invertebrate analogue of noradrenaline - in innate olfactory attraction to ethanol. We confirmed that preference is caused via an olfactory stimulus by dissecting the function of the olfactory co-receptor Orco (formally known as OR83b. Orco function is not required for ethanol recognition per se, however it plays a role in context dependent recognition of ethanol. Odor-evoked ethanol preference requires the function of Tbh (Tyramine β hydroxalyse, the rate-limiting enzyme of octopamine synthesis. In addition, neuronal activity in a subset of octopaminergic neurons is necessary for olfactory ethanol preference. Notably, a specific neuronal activation pattern of tyraminergic/octopaminergic neurons elicit preference and is therefore sufficient to induce preference. In contrast, dopamine dependent increase in locomotor activity is not sufficient for olfactory ethanol preference. Consistent with the role of noradrenaline in mammalian drug induced rewards, we provide evidence that in adult Drosophila the octopaminergic neurotransmitter functions as a reinforcer and that the molecular dissection of the innate attraction to ethanol uncovers the basic properties of a response selection system.

Evidence for the role of oxidative stress in the acetylation of histone H3 by ethanol in rat hepatocytes

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Choudhury, Mahua; Park, Pil-Hoon; Jackson, Daniel; Shukla, Shivendra D.

2010-01-01

The relationship between ethanol induced oxidative stress and acetylation of histone H3 at lysine 9 (H3AcK9) remains unknown and was therefore investigated in primary cultures of rat hepatocytes. Cells were treated with ethanol and a select group of pharmacological agents and the status of H3AcK9 and reactive oxygen species (ROS) were monitored. When hepatocytes were exposed to ethanol (50 mM, 24 hr) in the presence of N-acetyl cystein (ROS reducer) or dietary antioxidants (quercetin, resveratrol), or NADPH oxidase inhibitor apocynin, ethanol induced increases in ROS and H3AcK9, both were significantly reduced. On the other hand, l-buthionine-sulfoximine (ROS inducer) and inhibitor of mitochondrial complex I (rotenone) and III (antimycin) increased ethanol induced H3AcK9 (p<0.01). Oxidative stress also affected ethanol induced alcohol dehydrogenase 1 (ADH1) mRNA expression. These results demonstrate for the first time that oxidative stress is involved in the ethanol induced histone H3 acetylation in hepatocytes. PMID:20705415

Evidence for the involvement of 5-lipoxygenase products in ethanol-induced intestinal plasma protein loss

International Nuclear Information System (INIS)

Beck, I.T.; Boyd, A.J.; Dinda, P.K.

1988-01-01

In this study the authors investigated whether the products of 5-lipoxygenase (5-LO) were involved in the jejunal microvascular injury induced by intraluminal ethanol (ETH). A group of rabbits was given orally a selective inhibitor of 5-LO in two 10-mg doses, 24, and 2 h before the experiments. A jejunal segment was perfused with a control solution (control segment) and an adjacent segment with an ETH-containing solution (ETH-perfused segment). In a series of experiments, they measured 5-LO activity of the jejunal segments of both groups using the generation of leukotriene B 4 (LTB 4 ) as an index. In a second series of experiments, they determined the ETH-induced intraluminal protein loss, which was taken as a measure of mucosal microvascular damage. The ETH-induced increase in protein loss was significantly lower in the treated than in the untreated group. These findings suggest that products of 5-LO are involved in the ETH-induced jejunal microvascular injury

Zebrafish have an ethanol-inducible hepatic 4-nitrophenol hydroxylase that is not CYP2E1-like.

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Hartman, Jessica H; Kozal, Jordan S; Di Giulio, Richard T; Meyer, Joel N

2017-09-01

Zebrafish are an attractive model organism for toxicology; however, an important consideration in translating between species is xenobiotic metabolism/bioactivation. CYP2E1 metabolizes small hydrophobic molecules, e.g. ethanol, cigarette smoke, and diesel exhaust components. CYP2E1 is thought to only be conserved in mammals, but recent reports identified homologous zebrafish cytochrome P450s. Herein, ex vivo biochemical measurements show that unlike mammals, zebrafish possess a low-affinity 4-nitrophenol hydroxylase (K m ∼0.6 mM) in hepatic microsomes and mitochondria that is inducible only 1.5- to 2-fold by ethanol and is insensitive to 4-methylpyrazole inhibition. In closing, we suggest creating improved models to study CYP2E1 in zebrafish. Copyright © 2017 Elsevier B.V. All rights reserved.

Performance of carbon nanofiber supported Pd-Ni catalysts for electro-oxidation of ethanol in alkaline medium

Science.gov (United States)

Maiyalagan, T.; Scott, Keith

Carbon nanofibers (CNF) supported Pd-Ni nanoparticles have been prepared by chemical reduction with NaBH 4 as a reducing agent. The Pd-Ni/CNF catalysts were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and electrochemical voltammetry analysis. TEM showed that the Pd-Ni particles were quite uniformly distributed on the surface of the carbon nanofiber with an average particle size of 4.0 nm. The electro-catalytic activity of the Pd-Ni/CNF for oxidation of ethanol was examined by cyclic voltammetry (CV). The onset potential was 200 mV lower and the peak current density four times higher for ethanol oxidation for Pd-Ni/CNF compared to that for Pd/C. The effect of an increase in temperature from 20 to 60 °C had a great effect on increasing the ethanol oxidation activity.

Atomic force microscopy observation of lipopolysaccharide-induced cardiomyocyte cytoskeleton reorganization.

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Wang, Liqun; Chen, Tangting; Zhou, Xiang; Huang, Qiaobing; Jin, Chunhua

2013-08-01

We applied atomic force microscopy (AFM) to observe lipopolysaccharide (LPS)-induced intracellular cytoskeleton reorganization in primary cardiomyocytes from neonatal mouse. The nonionic detergent Triton X-100 was used to remove the membrane, soluble proteins, and organelles from the cell. The remaining cytoskeleton can then be directly visualized by AFM. Using three-dimensional technique of AFM, we were able to quantify the changes of cytoskeleton by the "density" and total "volume" of the cytoskeleton fibers. Compared to the control group, the density of cytoskeleton was remarkably decreased and the volume of cytoskeleton was significantly increased after LPS treatment, which suggests that LPS may induce the cytoskeleton reorganization and change the cardiomyocyte morphology. Copyright © 2013 Elsevier Ltd. All rights reserved.

Diosmin protects against ethanol-induced gastric injury in rats: novel anti-ulcer actions.

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Hany H Arab

Full Text Available Alcohol consumption has been commonly associated with gastric mucosal lesions including gastric ulcer. Diosmin (DIO is a natural citrus flavone with remarkable antioxidant and anti-inflammatory features that underlay its protection against cardiac, hepatic and renal injuries. However, its impact on gastric ulcer has not yet been elucidated. Thus, the current study aimed to investigate the potential protective effects of DIO against ethanol-induced gastric injury in rats. Pretreatment with DIO (100 mg/kg p.o. attenuated the severity of ethanol gastric mucosal damage as evidenced by lowering of ulcer index (UI scores, area of gastric lesions, histopathologic aberrations and leukocyte invasion. These actions were analogous to those exerted by the reference antiulcer sucralfate. DIO suppressed gastric inflammation by curbing of myeloperoxidase (MPO and tumor necrosis factor-α (TNF-α levels along with nuclear factor kappa B (NF-κB p65 expression. It also augmented the anti-inflammatory interleukin-10 (IL-10 levels. Meanwhile, DIO halted gastric oxidative stress via inhibition of lipid peroxides with concomitant enhancement of glutathione (GSH, glutathione peroxidase (GPx and the total antioxidant capacity (TAC. With respect to gastric mucosal apoptosis, DIO suppressed caspase-3 activity and cytochrome C (Cyt C with enhancement of the anti-apoptotic B cell lymphoma-2 (Bcl-2 in favor of cell survival. These favorable actions were associated with upregulation of the gastric cytoprotective prostaglandin E2 (PGE2 and nitric oxide (NO. Together, these findings accentuate the gastroprotective actions of DIO in ethanol gastric injury which were mediated via concerted multi-pronged actions, including suppression of gastric inflammation, oxidative stress and apoptosis besides boosting of the antioxidant and the cytoprotective defenses.

Cytochrome P-450 dependent ethanol oxidation. Kinetic isotope effects and absence of stereoselectivity

International Nuclear Information System (INIS)

Ekstroem, G.; Norsten, C.; Cronholm, T.; Ingelman-Sundberg, M.

1987-01-01

Deuterium isotope effects [/sup D/(V/K)] and stereoselectivity of ethanol oxidation in cytochrome P-450 containing systems and in the xanthine-xanthine oxidase system were compared with those of yeast alcohol dehydrogenase. The isotope effects were determined by using both a noncompetitive method, including incubation of unlabeled of [1,1- 2 H 2 ] ethanol at various concentrations, and a competitive method, where 1:1 mixtures of [1- 13 C]- and [ 2 H 6 ] ethanol or [2,2,2- 2 H 3 ]- and [1,1- 2 H 2 ] ethanol were incubated and the acetaldehyde formed was analyzed by gas chromatography/mass spectrometry. The /sup D/(V/K) isotope effects of the cytochrome P-450 dependent ethanol oxidation were about 4 with liver microsomes from imidazole-, phenobarbital- or acetone-treated rabbits or with microsomes from acetone- or ethanol-treated rats. Similar isotope effects were reached with reconstituted membranes containing the rabbit ethanol-inducible cytochrome P-450 (LMeb), whereas control rat microsomes and membranes containing rabbit phenobarbital-inducible P-450 LM 2 oxidized the alcohol with /sup D/(V/K) of about 2.8 and 1.8, respectively. Addition of Fe/sup III/EDTA either to microsomes from phenobarbital-treated rabbits or to membranes containing P-450 LMeb significantly lowered the isotope effect. Incubations of all cytochrome P-450 containing systems of the xanthine-xanthine oxidase systems with (1R)- and (1S)-[1- 2 H] ethanol, revealed, taking the isotope effects into account, that 44-66% of the ethanol oxidized had lost the 1-pro-R hydrogen. The data indicate that cytochrome P-450 dependent ethanol oxidation is not stereospecific and that cleavage of the C 1 -H bond appears to be a rate-determining step in the catalysis by the ethanol-inducible form of P-450. The contribution of hydroxyl radicals in ethanol oxidation by the various enzymic systems is discussed

Cholesterol Enhances the Toxic Effect of Ethanol and Acetaldehyde in Primary Mouse Hepatocytes

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Anayelly López-Islas

2016-01-01

Full Text Available Obesity and alcohol consumption are risk factors for hepatic steatosis, and both commonly coexist. Our objective was to evaluate the effect of ethanol and acetaldehyde on primary hepatocytes obtained from mice fed for two days with a high cholesterol (HC diet. HC hepatocytes increased lipid and cholesterol content. HC diet sensitized hepatocytes to the toxic effect of ethanol and acetaldehyde. Cyp2E1 content increased with HC diet, as well as in those treated with ethanol or acetaldehyde, while the activity of this enzyme determined in microsomes increased in the HC and in all ethanol treated hepatocytes, HC and CW. Oxidized proteins were increased in the HC cultures treated or not with the toxins. Transmission electron microscopy showed endoplasmic reticulum (ER stress and megamitochondria in hepatocytes treated with ethanol as in HC and the ethanol HC treated hepatocytes. ER stress determined by PERK content was increased in ethanol treated hepatocytes from HC mice and CW. Nuclear translocation of ATF6 was observed in HC hepatocytes treated with ethanol, results that indicate that lipids overload and ethanol treatment favor ER stress. Oxidative stress, ER stress, and mitochondrial damage underlie potential mechanisms for increased damage in steatotic hepatocyte treated with ethanol.

Effects of tryptophan derivatives and β-carboline alkaloids on radiation- and peroxide-induced transformations of ethanol

International Nuclear Information System (INIS)

Sverdlov, R.L.; Brinkevich, S.D.; Shadyro, O.I.

2014-01-01

The subject of this study was investigation of interactions of tryptophan and its derivatives, including structurally related β-carboline alkaloids with oxygen- and carbon-centered radicals being formed during radiation- and peroxide-induced transformations of ethanol. It was shown that the above named compounds suppressed recombination and disproportionation reactions of α-hydroxyethyl radicals. The inhibitory effects of tryptophan, 5-hydroxytryptophan and serotonin were mainly realized by means of reduction and addition reactions, while those of β-carboline alkaloids – harmine, harmane and harmaline – were due to oxidation reactions. Melatonin displayed low reactivity towards α-hydroxyethyl radicals. Tryptophan derivatives and β-carboline alkaloids were found to inhibit radiation-induced oxidation of ethanol while being virtually not used up. The low transformation yields of tryptophan, 5-hydroxytryptophan and serotonin, as well as β-carboline alkaloids, indicate their capability of regeneration, which could occur on interaction of tryptophan with O ·− 2 and HO · 2 , or on oxidation of α-hydroxyethyl radicals by β-carboline alkaloids. - Highlights: • Tryptophan, 5-hydroxytryptophane and serotonin can reduce or add α-HER. • β-Carboline alkaloids – harmane, harmine, harmaline – can oxidize α-HER. • Tryptophan and its derivatives can reduce oxygen-centered radicals

Environemtnal benefits of the Brazilian Ethanol Programme

International Nuclear Information System (INIS)

La Rovere, E.L.; Audinet, P.

1993-01-01

After nearly twenty years since it was first launched, the Brazilian Ethanol Programme to data remains the largest commercial application of biomass for energy production and use in the world. It succeeded in demonstrating the technical feasibility of large scale ethanol production from sugar cane and its use to fuel car engines. On social and economic grounds, however, its evaluation is less positive. The purpose of this study is to provide an updated overview of the perspectives for the Ethanol Programme under the light of increasingly important local and global environmental concerns. Major results show that after oil prices supported upon the basis of its contribution to curb the increase of air pollution in Brazilian cities and of the greenhouse effect. It is concluded that the very survival of the Ethanol Programme, depends upon adequate economic compensation considering its global environmental benefits. These are appraised with two scenarios based on the use of a Markal-like model to define the range and costs of curbing greenhouse gases with a policy aiming at extending the Ethanol Programme

Oxidative and Non-Oxidative Metabolomics of Ethanol.

Science.gov (United States)

Dinis-Oliveira, Ricardo Jorge

2016-01-01

It is well known that ethanol can cause significant morbidity and mortality, and much of the related toxic effects can be explained by its metabolic profile. This work performs a complete review of the metabolism of ethanol focusing on both major and minor metabolites. An exhaustive literature search was carried out using textual and structural queries for ethanol and related known metabolizing enzymes and metabolites. The main pathway of metabolism is catalyzed by cytosolic alcohol dehydrogenase, which exhibits multiple isoenzymes and genetic polymorphisms with clinical and forensic implications. Another two oxidative routes, the highly inducible CYP2E1 system and peroxisomal catalase may acquire relevance under specific circumstances. In addition to oxidative metabolism, ethanol also originates minor metabolites such as ethyl glucuronide, ethyl sulfate, ethyl phosphate, ethyl nitrite, phosphatidylethanol and fatty acid ethyl esters. These metabolites represent alternative biomarkers since they can be detected several hours or days after ethanol exposure. It is expected that knowing the metabolomics of ethanol may provide additional insights to better understand the toxicological effects and the variability of dose response.

Chronic intermittent ethanol inhalation increases ethanol self-administration in both C57BL/6J and DBA/2J mice.

Science.gov (United States)

McCool, Brian A; Chappell, Ann M

2015-03-01

Inbred mouse strains provide significant opportunities to understand the genetic mechanisms controlling ethanol-directed behaviors and neurobiology. They have been specifically employed to understand cellular mechanisms contributing to ethanol consumption, acute intoxication, and sensitivities to chronic effects. However, limited ethanol consumption by some strains has restricted our understanding of clinically relevant endpoints such as dependence-related ethanol intake. Previous work with a novel tastant-substitution procedure using monosodium glutamate (MSG or umami flavor) has shown that the procedure greatly enhances ethanol consumption by mouse strains that express limited drinking phenotypes using other methods. In the current study, we employ this MSG-substitution procedure to examine how ethanol dependence, induced with passive vapor inhalation, modifies ethanol drinking in C57BL/6J and DBA/2J mice. These strains represent 'high' and 'low' drinking phenotypes, respectively. We found that the MSG substitution greatly facilitates ethanol drinking in both strains, and likewise, ethanol dependence increased ethanol consumption regardless of strain. However, DBA/2J mice exhibited greater sensitivity dependence-enhanced drinking, as represented by consumption behaviors directed at lower ethanol concentrations and relative to baseline intake levels. DBA/2J mice also exhibited significant withdrawal-associated anxiety-like behavior while C57BL/6J mice did not. These findings suggest that the MSG-substitution procedure can be employed to examine dependence-enhanced ethanol consumption across a range of drinking phenotypes, and that C57BL/6J and DBA/2J mice may represent unique neurobehavioral pathways for developing dependence-enhanced ethanol consumption. Copyright © 2015 Elsevier Inc. All rights reserved.

Data on the effects of losartan on protein expression, vascular reactivity and antioxidant capacity in the aorta of ethanol-treated rats

Directory of Open Access Journals (Sweden)

Carla S. Ceron

2017-04-01

Full Text Available We describe the effects of losartan, a selective AT1 receptor antagonist on the alterations induced by treatment with ethanol in the rat aorta. The data shown here are related to the article entitled “Angiotensin type 1 receptor mediates chronic ethanol consumption-induced hypertension and vascular oxidative stress” (P. Passaglia, C.S. Ceron, A.S. Mecawi, J. Antunes-Rodrigues, E.B. Coelho, C.R. Tirapelli, 2015 [1]. Here we include new data on the protective effect of losartan against ethanol-induced oxidative stress. Male Wistar rats treated for 2 weeks with ethanol (20%, vol./vol. exhibited increased aortic production of reactive oxygen species (ROS and losartan (10 mg/kg/day; p.o. gavage prevented this response. Ethanol did not alter the expression of eNOS in the rat aorta. Losartan prevented ethanol-induced increase in the aortic expression of nNOS. Neither ethanol nor losartan affected superoxide dismutase (SOD or catalase (CAT activities in the rat aorta. Treatment with ethanol increased the contraction induced by phenylephrine in both endothelium-intact and endothelium-denuded aortas and these responses were prevented by losartan. Conversely, neither ethanol nor losartan affected the endothelium-dependent relaxation induced by acetylcholine.

Hydrogen production by ethanol steam reforming over co-hydrotalcites having basic sites

Energy Technology Data Exchange (ETDEWEB)

Contreras, J.L.; Salmones, J.; Garcia, L.A.; Ponce, A.; Zeifert, B.; Fuentes, G.A. [Univ. Autonoma Metropolitana-Azcapotzalco, Mexico City (Mexico); Contreras, J.L.; Salmones, J.; Garcia, L.A.; Ponce, A.; Zeifert, B.; Fuentes, G.A. [Inst. Politecnico Nacional, Mexico City (Mexico); Contreras, J.L.; Salmones, J.; Garcia, L.A.; Ponce, A.; Zeifert, B.; Fuentes, G.A. [Univ. Autonoma Metropolitana-Iztapalapa, Mexico City (Mexico)

2008-04-15

The catalytic steam reforming process can be used to produce hydrogen from ethanol for use in fuel cells. In comparison to methanol or gasoline, ethanol offers many advantages, notably, it is a renewable resource and neutral with respect to emissions of carbon dioxide (CO{sub 2}); it is less toxic; it can be readily stored without handling risk; and it can be obtained in large quantities from biomass. The reaction of ethanol with steam is strongly endothermic and can form undesirable products during the reaction. This article presented a study that combined, for the first time, the catalytic properties of cobalt (Co) with a new family of supports that are the hydrotalcites of high surface area and with basic sites. Co/Hydrotalcite catalysts were prepared, characterized and evaluated during the steam reforming of ethanol from 500 to 650 degrees Celsius. The article discussed the experiment, including the preparation of catalysts; characterization of solids; and catalytic evaluation. Scanning electron microscopy and x-ray diffraction studies were also described. Results were described in terms of area and pore volume distribution; thermogravimetric analysis and differential thermal analysis; temperature-programmed desorption (TPD) of CO{sub 2}; scanning electron microscopy; x-ray diffraction; the crystalline nature of cobalt; and ethanol steam-reforming reaction. It was concluded that the Co concentration was enriched on the hydrotalcite surface. In addition, a direct relationship between the Co concentration and the total basicity was found. A direct relationship between basicity and the conversion was also found. 27 refs., 3 tabs., 12 figs.

The use of fluorescence microscopy and image analysis for rapid detection of non-producing revertant cells of Synechocystis sp. PCC6803 and Synechococcus sp. PCC7002.

Science.gov (United States)

Schulze, Katja; Lang, Imke; Enke, Heike; Grohme, Diana; Frohme, Marcus

2015-04-17

Ethanol production via genetically engineered cyanobacteria is a promising solution for the production of biofuels. Through the introduction of a pyruvate decarboxylase and alcohol dehydrogenase direct ethanol production becomes possible within the cells. However, during cultivation genetic instability can lead to mutations and thus loss of ethanol production. Cells then revert back to the wild type phenotype. A method for a rapid and simple detection of these non-producing revertant cells in an ethanol producing cell population is an important quality control measure in order to predict genetic stability and the longevity of a producing culture. Several comparable cultivation experiments revealed a difference in the pigmentation for non-producing and producing cells: the accessory pigment phycocyanin (PC) is reduced in case of the ethanol producer, resulting in a yellowish appearance of the culture. Microarray and western blot studies of Synechocystis sp. PCC6803 and Synechococcus sp. PCC7002 confirmed this PC reduction on the level of RNA and protein. Based on these findings we developed a method for fluorescence microscopy in order to distinguish producing and non-producing cells with respect to their pigmentation phenotype. By applying a specific filter set the emitted fluorescence of a producer cell with a reduced PC content appeared orange. The emitted fluorescence of a non-producing cell with a wt pigmentation phenotype was detected in red, and dead cells in green. In an automated process multiple images of each sample were taken and analyzed with a plugin for the image analysis software ImageJ to identify dead (green), non-producing (red) and producing (orange) cells. The results of the presented validation experiments revealed a good identification with 98 % red cells in the wt sample and 90 % orange cells in the producer sample. The detected wt pigmentation phenotype (red cells) in the producer sample were either not fully induced yet (in 48 h induced

CB1R-Mediated Activation of Caspase-3 Causes Epigenetic and Neurobehavioral Abnormalities in Postnatal Ethanol-Exposed Mice

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Shivakumar Subbanna

2018-02-01

Full Text Available Alcohol exposure can affect brain development, leading to long-lasting behavioral problems, including cognitive impairment, which together is defined as fetal alcohol spectrum disorder (FASD. However, the fundamental mechanisms through which this occurs are largely unknown. In this study, we report that the exposure of postnatal day 7 (P7 mice to ethanol activates caspase-3 via cannabinoid receptor type-1 (CB1R in neonatal mice and causes a reduction in methylated DNA binding protein (MeCP2 levels. The developmental expression of MeCP2 in mice is closely correlated with synaptogenesis and neuronal maturation. It was shown that ethanol treatment of P7 mice enhanced Mecp2 mRNA levels but reduced protein levels. The genetic deletion of CB1R prevented, and administration of a CB1R antagonist before ethanol treatment of P7 mice inhibited caspase-3 activation. Additionally, it reversed the loss of MeCP2 protein, cAMP response element binding protein (CREB activation, and activity-regulated cytoskeleton-associated protein (Arc expression. The inhibition of caspase-3 activity prior to ethanol administration prevented ethanol-induced loss of MeCP2, CREB activation, epigenetic regulation of Arc expression, long-term potentiation (LTP, spatial memory deficits and activity-dependent impairment of several signaling molecules, including MeCP2, in adult mice. Collectively, these results reveal that the ethanol-induced CB1R-mediated activation of caspase-3 degrades the MeCP2 protein in the P7 mouse brain and causes long-lasting neurobehavioral deficits in adult mice. This CB1R-mediated instability of MeCP2 during active synaptic maturation may disrupt synaptic circuit maturation and lead to neurobehavioral abnormalities, as observed in this animal model of FASD.

Elucidation of Compression-Induced Surface Crystallization in Amorphous Tablets Using Sum Frequency Generation (SFG) Microscopy.

Science.gov (United States)

Mah, Pei T; Novakovic, Dunja; Saarinen, Jukka; Van Landeghem, Stijn; Peltonen, Leena; Laaksonen, Timo; Isomäki, Antti; Strachan, Clare J

2017-05-01

To investigate the effect of compression on the crystallization behavior in amorphous tablets using sum frequency generation (SFG) microscopy imaging and more established analytical methods. Tablets containing neat amorphous griseofulvin with/without excipients (silica, hydroxypropyl methylcellulose acetate succinate (HPMCAS), microcrystalline cellulose (MCC) and polyethylene glycol (PEG)) were prepared. They were analyzed upon preparation and storage using attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, scanning electron microscopy (SEM) and SFG microscopy. Compression-induced crystallization occurred predominantly on the surface of the neat amorphous griseofulvin tablets, with minimal crystallinity being detected in the core of the tablets. The presence of various types of excipients was not able to mitigate the compression-induced surface crystallization of the amorphous griseofulvin tablets. However, the excipients affected the crystallization rate of amorphous griseofulvin in the core of the tablet upon compression and storage. SFG microscopy can be used in combination with ATR-FTIR spectroscopy and SEM to understand the crystallization behaviour of amorphous tablets upon compression and storage. When selecting excipients for amorphous formulations, it is important to consider the effect of the excipients on the physical stability of the amorphous formulations.

The use of docosahexaenoic acid supplementation to ameliorate the hyperactivity of rat pups induced by in utero ethanol exposure

OpenAIRE

Furuya, Hiroyuki; Aikawa, Hiroyuki; Yoshida, Takahiko; Okazaki, Isao

2000-01-01

It has been demonstrated thatin utero ethanol (EtOH) exposure induces hyperactive behavior and learning disturbances in offspring. In order to investigate the effects of docosahexaenoic acid (DHA) on these neurobehavioral dysfunctions of rat pups induced byin utero EtOH exposure, pregnant Wistar rats were divided into four treatment groups depending on the type of oil added to the diet and drinking water as follows; (a) 5% safflower oil with tap water (TW/n-6), (b) 3% safflower oil and 2% DHA...

PdRu/C catalysts for ethanol oxidation in anion-exchange membrane direct ethanol fuel cells

Science.gov (United States)

Ma, Liang; He, Hui; Hsu, Andrew; Chen, Rongrong

2013-11-01

Carbon supported PdRu catalysts with various Pd:Ru atomic ratios were synthesized by impregnation method, and characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), electrochemical half-cell tests, and the anion-exchange membrane direct ethanol fuel cell (AEM-DEFC) tests. XRD results suggest that the PdRu metal exists on carbon support in an alloy form. TEM study shows that the bimetallic PdRu/C catalysts have slightly smaller average particle size than the single metal Pd/C catalyst. Lower onset potential and peak potential and much higher steady state current for ethanol oxidation in alkaline media were observed on the bimetallic catalysts (PdxRuy/C) than on the Pd/C, while the activity for ethanol oxidation on the pure Ru/C was not noticeable. By using Pd/C anode catalysts and MnO2 cathode catalysts, AEM-DEFCs free from the expensive Pt catalyst were assembled. The AEM DEFC using the bimetallic Pd3Ru/C anode catalyst showed a peak power density as high as 176 mW cm-2 at 80 °C, about 1.8 times higher than that using the single metal Pd/C catalyst. The role of Ru for enhancing the EOR activity of Pd/C catalysts is discussed.

Fabrication of Te@Au core-shell hybrids for efficient ethanol oxidation

Science.gov (United States)

Jin, Huile; Wang, Demeng; Zhao, Yuewu; Zhou, Huan; Wang, Shun; Wang, Jichang

2012-10-01

Using Au nanoparticles to catalyze the oxidation of alcohols has garnered increasing attention due to its potential application in direct alcohol fuel cells. In this research Te@Au core-shell hybrids were fabricated for the catalytic oxidation of ethanol, where the preparation procedure involved the initial production of Te crystals with different microstructures and the subsequent utilization of the Te crystal as a template and reducing agent for the production of Te@Au hybrids. The as-prepared core-shell hybrids were characterized by scanning electron microscopy, transmission electron microscopy, energy-dispersive X-ray spectroscopy, and X-ray diffraction techniques. Electrochemical measurements illustrate that the hybrids have great electrocatalytic activity and stability toward ethanol oxidation in alkaline media. The enhanced electrocatalytic property may be attributed to the cooperative effects between the metal and semiconductor and the presence of a large number of active sites on the hybrids surface.

Performance of carbon nanofiber supported Pd-Ni catalysts for electro-oxidation of ethanol in alkaline medium

Energy Technology Data Exchange (ETDEWEB)

Maiyalagan, T.; Scott, Keith [School of Chemical Engineering and Advanced Materials, University of Newcastle upon Tyne, Newcastle upon Tyne NE1 7RU (United Kingdom)

2010-08-15

Carbon nanofibers (CNF) supported Pd-Ni nanoparticles have been prepared by chemical reduction with NaBH{sub 4} as a reducing agent. The Pd-Ni/CNF catalysts were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and electrochemical voltammetry analysis. TEM showed that the Pd-Ni particles were quite uniformly distributed on the surface of the carbon nanofiber with an average particle size of 4.0 nm. The electro-catalytic activity of the Pd-Ni/CNF for oxidation of ethanol was examined by cyclic voltammetry (CV). The onset potential was 200 mV lower and the peak current density four times higher for ethanol oxidation for Pd-Ni/CNF compared to that for Pd/C. The effect of an increase in temperature from 20 to 60 C had a great effect on increasing the ethanol oxidation activity. (author)

Catalase inhibition in the Arcuate nucleus blocks ethanol effects on the locomotor activity of rats.

Science.gov (United States)

Sanchis-Segura, Carles; Correa, Mercé; Miquel, Marta; Aragon, Carlos M G

2005-03-07

Previous studies have demonstrated that there is a bidirectional modulation of ethanol-induced locomotion produced by drugs that regulate brain catalase activity. In the present study we have assessed the effect in rats of intraperitoneal, intraventricular or intracraneal administration of the catalase inhibitor sodium azide in the locomotor changes observed after ethanol (1 g/kg) administration. Our results show that sodium azide prevents the effects of ethanol in rats locomotion not only when sodium azide was systemically administered but also when it was intraventricularly injected, then confirming that the interaction between catalase and ethanol takes place in Central Nervous System (CNS). Even more interestingly, the same results were observed when sodium azide administration was restricted to the hypothalamic Arcuate nucleus (ARC), a brain region which has one of the highest levels of expression of catalase. Therefore, the results of the present study not only confirm a role for brain catalase in the mediation of ethanol-induced locomotor changes in rodents but also point to the ARC as a major neuroanatomical location for this interaction. These results are in agreement with our reports showing that ethanol-induced locomotor changes are clearly dependent of the ARC integrity and, especially of the POMc-synthesising neurons of this nucleus. According to these data we propose a model in which ethanol oxidation via catalase could produce acetaldehyde into the ARC and to promote a release of beta-endorphins that would activate opioid receptors to produce locomotion and other ethanol-induced neurobehavioural changes.

Anti-Ulcerogenic Properties of Lycium chinense Mill Extracts against Ethanol-Induced Acute Gastric Lesion in Animal Models and Its Active Constituents

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Opeyemi J. Olatunji

2015-12-01

Full Text Available The objective of this study was to explore the gastroprotective properties of the aerial part of Lycium chinense Mill (LCA against ethanol-induced gastric mucosa lesions in mice models. Administration of LCA at doses of 50, 100, 200 and 400 mg/kg body weight prior to ethanol consumption dose dependently inhibited gastric ulcers. The gastric mucosal injury was analyzed by gastric juice acidity, glutathione (GSH, superoxide dismutase (SOD, malondialdehyde (MDA, myeloperoxidase (MPO activities. Furthermore, the levels of the inflammatory mediators, tumor necrosis factor-α (TNF-α, interleukin-6 (IL-6 and interleukin-1β (IL-1β in serum were also analyzed using ELISA. Pathological changes were also observed with the aid of hematoxylin-eosin (HE staining. Our results indicated that LCA significantly reduced the levels of MPO, MDA and increased SOD and GSH activities. Furthermore, LCA also significantly inhibited the levels of TNF-α, IL-6, and IL-1β in the serum of ulcerated mice in a dose dependent manner. Immunohistological analysis indicated that LCA also significantly attenuated the overexpression of nuclear factor-κB in pretreated mice models. This findings suggests Lycium chinense Mill possesses gastroprotective properties against ethanol-induced gastric injury and could be a possible therapeutic intervention in the treatment and management of gastric ulcers.

Ethanol induces MAP2 changes in organotypic hippocampal slice cultures

DEFF Research Database (Denmark)

Noraberg, J; Zimmer, J

1998-01-01

loss of CA3 pyramidal cells and moderate loss of dentate granule cells, as seen in vivo. The results indicate that brain slice cultures combined with immunostaining for cytoskeleton and neuronal markers can be used for studies of ethanol and organic solvent neurotoxicity.......Microtubule-associated protein 2 (MAP2) and neuron-specific protein (NeuN) immunostains were used to demonstrate neurotoxic effects in mature hippocampal slice cultures exposed to ethanol (50, 100, 200 mM) for 4 weeks. At the low dose the density of MAP2 immunostaining in the dentate molecular...... layer was 118% of the control cultures, with no detectable changes in CA1 and CA3. At 100 mM no changes were detected, while 200 mM ethanol significantly reduced the MAP2 density in both dentate (19%) and hippocampal dendritic fields (CA3, 52%; CA1, 55%). At this dose NeuN staining showed considerable...

Seeing in 4D with electrons: development of ultrafast electron microscopy at Caltech

International Nuclear Information System (INIS)

Baskin, J.S.; Zewail, A.H.

2014-01-01

The vision to develop 4D electron microscopy, a union of the capabilities of electron microscopy with ultrafast techniques to capture clearly defined images of the nano-scale structure of a material at each step in the course of its chemical or physical transformations, has been pursued at Caltech for the last decade. In this contribution, we will give a brief overview of the capabilities of three currently active Caltech 4D microscopy laboratories. Ongoing work is illustrated by a description of the most recent application of photon-induced near-field electron microscopy (PINEM), a field made possible only by the development of the 4D ultrafast electron microscopy (UEM). An appendix gives the various applications made so far and the historic roots of the development at Caltech. (authors)

Low-Dose Ethanol Preconditioning Protects Against Oxygen-Glucose Deprivation/Reoxygenation-Induced Neuronal Injury By Activating Large Conductance, Ca2+-Activated K+ Channels In Vitro

Institute of Scientific and Technical Information of China (English)

Fang Su; An-Chen Guo; Wei-Wei Li; Yi-Long Zhao; Zheng-Yi Qu; Yong-Jun Wang; Qun Wang; Yu-Lan Zhu

2017-01-01

Increasing evidence suggests that low to moderate ethanol ingestion protects against the deleterious effects of subsequent ischemia/reperfusion;however,the underlying mechanism has not been elucidated.In the present study,we showed that expression of the neuronal large-conductance,Ca2+-activated K+ channel (BKCa) α-subunit was upregulated in cultured neurons exposed to oxygen-glucose deprivatior/reoxygenation (OGD/R) compared with controls.Preconditioning with low-dose ethanol (10 mmol/L) increased cell survival rate in neurons subjected to OGD/R,attenuated the OGD/R-induced elevation of cytosolic Ca2+ levels,and reduced the number of apoptotic neurons.Western blots revealed that ethanol preconditioning upregulated expression of the anti-apoptotic protein Bcl-2 and downregulated the pro-apoptotic protein Bax.The protective effect of ethanol preconditioning was antagonized by a BKCa channel inhibitor,paxilline.Inside-out patches in primary neurons also demonstrated the direct activation of the BKCa channel by 10 mmol/L ethanol.The above results indicated that low-dose ethanol preconditioning exerts its neuroprotective effects by attenuating the elevation of cytosolic Ca2+ and preventing neuronal apoptosis,and this is mediated by BKCa channel activation.

Low-Dose Ethanol Preconditioning Protects Against Oxygen-Glucose Deprivation/Reoxygenation-Induced Neuronal Injury By Activating Large Conductance, Ca2+-Activated K+ Channels In Vitro.

Science.gov (United States)

Su, Fang; Guo, An-Chen; Li, Wei-Wei; Zhao, Yi-Long; Qu, Zheng-Yi; Wang, Yong-Jun; Wang, Qun; Zhu, Yu-Lan

2017-02-01

Increasing evidence suggests that low to moderate ethanol ingestion protects against the deleterious effects of subsequent ischemia/reperfusion; however, the underlying mechanism has not been elucidated. In the present study, we showed that expression of the neuronal large-conductance, Ca 2+ -activated K + channel (BK Ca ) α-subunit was upregulated in cultured neurons exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) compared with controls. Preconditioning with low-dose ethanol (10 mmol/L) increased cell survival rate in neurons subjected to OGD/R, attenuated the OGD/R-induced elevation of cytosolic Ca 2+ levels, and reduced the number of apoptotic neurons. Western blots revealed that ethanol preconditioning upregulated expression of the anti-apoptotic protein Bcl-2 and downregulated the pro-apoptotic protein Bax. The protective effect of ethanol preconditioning was antagonized by a BK Ca channel inhibitor, paxilline. Inside-out patches in primary neurons also demonstrated the direct activation of the BK Ca channel by 10 mmol/L ethanol. The above results indicated that low-dose ethanol preconditioning exerts its neuroprotective effects by attenuating the elevation of cytosolic Ca 2+ and preventing neuronal apoptosis, and this is mediated by BK Ca channel activation.

Laser induced florescence: application to spectroscopy and new microscopy imaging methods

International Nuclear Information System (INIS)

Galaup, L. P.

2012-01-01

Laser induced fluorescence is one of the light using techniques which allows the highest sensitivity for atoms and molecules detection, up to the single atom or single molecule level. This field is much too large for an extensive review; therefor we have chosen to focus on two main points: 1- the observation of laser stimulated fluorescence in phthalocyanine and porphyrin like molecules in rare gas and nitrogen matrices at low temperatures. 2- the presentation of laser induced fluorescence techniques suitable for achieving ultra-high spatial resolution imaging, below the diffraction limit of conventional microscopy, thanks to highly fluorescent molecules to be used as biological markers. (Author)

Radiation-chemical transformations of coumarins in ethanolic solutions

International Nuclear Information System (INIS)

Samovich, S.N.; Brinkevich, S.D.; Edimecheva, I.P.; Shadyro, O.I.

2014-01-01

Effects of coumarin and its derivatives on product formation during radiolysis of deaerated and oxygenated ethanol were investigated. The data obtained in this study indicate that coumarin, 4-hydroxycoumarin and warfarin effectively oxidized α-hydroxyethyl radicals (α-HER), while esculetin and fraxetin predominantly reduced the above named intermediates. Coumarin, esculetin and fraxetin were able to add α-HER to the double carbon–carbon bond of the pyrone ring to form stable products with molecular masses exceeding those of the starting molecules. Coumarin, warfarin, esculetin and fraxetin were shown to display antioxidant activity during radiation-induced oxidation of ethanol. - Highlights: • Coumarin, 4-hydroxycoumarin and warfarin oxidize α-hydroxyethyl radicals. • Esculetin and fraxetin predominantly reduce α-hydroxyethyl radicals. • Coumarins add α-hydroxyethyl radicals to the C=C bonds of the pyrone ring. • Coumarins display antioxidant activity on radiation-induced oxidation of ethanol

Precision platform for convex lens-induced confinement microscopy

Science.gov (United States)

Berard, Daniel; McFaul, Christopher M. J.; Leith, Jason S.; Arsenault, Adriel K. J.; Michaud, François; Leslie, Sabrina R.

2013-10-01

We present the conception, fabrication, and demonstration of a versatile, computer-controlled microscopy device which transforms a standard inverted fluorescence microscope into a precision single-molecule imaging station. The device uses the principle of convex lens-induced confinement [S. R. Leslie, A. P. Fields, and A. E. Cohen, Anal. Chem. 82, 6224 (2010)], which employs a tunable imaging chamber to enhance background rejection and extend diffusion-limited observation periods. Using nanopositioning stages, this device achieves repeatable and dynamic control over the geometry of the sample chamber on scales as small as the size of individual molecules, enabling regulation of their configurations and dynamics. Using microfluidics, this device enables serial insertion as well as sample recovery, facilitating temporally controlled, high-throughput measurements of multiple reagents. We report on the simulation and experimental characterization of this tunable chamber geometry, and its influence upon the diffusion and conformations of DNA molecules over extended observation periods. This new microscopy platform has the potential to capture, probe, and influence the configurations of single molecules, with dramatically improved imaging conditions in comparison to existing technologies. These capabilities are of immediate interest to a wide range of research and industry sectors in biotechnology, biophysics, materials, and chemistry.

Ethanol-related behaviors in mice lacking the sigma-1 receptor.

Science.gov (United States)

Valenza, Marta; DiLeo, Alyssa; Steardo, Luca; Cottone, Pietro; Sabino, Valentina

2016-01-15

The Sigma-1 receptor (Sig-1R) is a chaperone protein that has been implicated in drug abuse and addiction. Multiple studies have characterized the role the Sig-1R plays in psychostimulant addiction; however, fewer studies have specifically investigated its role in alcohol addiction. We have previously shown that antagonism of the Sig-1R reduces excessive drinking and motivation to drink, whereas agonism induces binge-like drinking in rodents. The objectives of these studies were to investigate the impact of Sig-1R gene deletion in C57Bl/6J mice on ethanol drinking and other ethanol-related behaviors. We used an extensive panel of behavioral tests to examine ethanol actions in male, adult mice lacking Oprs1, the gene encoding the Sig-1R. To compare ethanol drinking behavior, Sig-1 knockout (KO) and wild type (WT) mice were subject to a two-bottle choice, continuous access paradigm with different concentrations of ethanol (3-20% v/v) vs. water. Consumption of sweet and bitter solutions was also assessed in Sig-1R KO and WT mice. Finally, motor stimulant sensitivity, taste aversion and ataxic effects of ethanol were assessed. Sig-1R KO mice displayed higher ethanol intake compared to WT mice; the two genotypes did not differ in their sweet or bitter taste perception. Sig-1R KO mice showed lower sensitivity to ethanol stimulant effects, but greater sensitivity to its taste aversive effects. Ethanol-induced sedation was instead unaltered in the mutants. Our results prove that the deletion of the Sig-1R increases ethanol consumption, likely by decreasing its rewarding effects, and therefore indicating that the Sig-1R is involved in modulation of the reinforcing effects of alcohol. Copyright © 2015 Elsevier B.V. All rights reserved.

Induction of morphological changes in death-induced cancer cells monitored by holographic microscopy.

Science.gov (United States)

El-Schich, Zahra; Mölder, Anna; Tassidis, Helena; Härkönen, Pirkko; Falck Miniotis, Maria; Gjörloff Wingren, Anette

2015-03-01

We are using the label-free technique of holographic microscopy to analyze cellular parameters including cell number, confluence, cellular volume and area directly in the cell culture environment. We show that death-induced cells can be distinguished from untreated counterparts by the use of holographic microscopy, and we demonstrate its capability for cell death assessment. Morphological analysis of two representative cell lines (L929 and DU145) was performed in the culture flasks without any prior cell detachment. The two cell lines were treated with the anti-tumour agent etoposide for 1-3days. Measurements by holographic microscopy showed significant differences in average cell number, confluence, volume and area when comparing etoposide-treated with untreated cells. The cell volume of the treated cell lines was initially increased at early time-points. By time, cells decreased in volume, especially when treated with high doses of etoposide. In conclusion, we have shown that holographic microscopy allows label-free and completely non-invasive morphological measurements of cell growth, viability and death. Future applications could include real-time monitoring of these holographic microscopy parameters in cells in response to clinically relevant compounds. Copyright © 2015 Elsevier Inc. All rights reserved.

Tolerance to and cross tolerance between ethanol and nicotine.

Science.gov (United States)

Collins, A C; Burch, J B; de Fiebre, C M; Marks, M J

1988-02-01

Female DBA mice were subjected to one of four treatments: ethanol-containing or control diets, nicotine (0.2, 1.0, 5.0 mg/kg/hr) infusion or saline infusion. After removal from the liquid diets or cessation of infusion, the animals were challenged with an acute dose of ethanol or nicotine. Chronic ethanol-fed mice were tolerant to the effects of ethanol on body temperature and open field activity and were cross tolerant to the effects of nicotine on body temperature and heart rate. Nicotine infused animals were tolerant to the effects of nicotine on body temperature and rotarod performance and were cross tolerant to the effects of ethanol on body temperature. Ethanol-induced sleep time was decreased in chronic ethanol- but not chronic nicotine-treated mice. Chronic drug treatment did not alter the elimination rate of either drug. Chronic ethanol treatment did not alter the number or affinity of brain nicotinic receptors whereas chronic nicotine treatment elicited an increase in the number of [3H]-nicotine binding sites. Tolerance and cross tolerance between ethanol and nicotine is discussed in terms of potential effects on desensitization of brain nicotinic receptors.

Dielectric breakdown of ultrathin aluminum oxide films induced by scanning tunneling microscopy

International Nuclear Information System (INIS)

Magtoto, N. P.; Niu, C.; Ekstrom, B. M.; Addepalli, S.; Kelber, J. A.

2000-01-01

Dielectric breakdown of 7-Aa-thick Al 2 O 3 (111) films grown on Ni 3 Al(111) under ultrahigh vacuum conditions is induced by increasing the bias voltage on the scanning tunneling microscopy tip under constant current feedback. Breakdown is marked by the precipitous retreat of the tip from the surface, and the formation of an elevated feature in the scanning tunneling microscopy image, typically greater than 5 nm high and ∼100 nm in diameter. Constant height measurements performed at tip/sample distances of 1 nm or less yield no tip/substrate physical interaction, indicating that such features do not result from mass transport. Consistent with this, current/voltage measurements within the affected regions indicate linear behavior, in contrast to a band gap of 1.5 eV observed at unaffected regions of the oxide surface. A threshold electric field value of 11±1 MV cm -1 is required to induce breakdown, in good agreement with extrapolated values from capacitance measurements on thicker oxides. (c) 2000 American Institute of Physics

Effects of the kappa opioid receptor antagonist MR-2266-BS on the acquisition of ethanol preference

Energy Technology Data Exchange (ETDEWEB)

Sandi, C.; Borrell, J.; Guaza, C. (Cajal Institute, Madrid (Spain))

1990-01-01

Using a paradigm by which rats forced to drink a weak ethanol solution develop ethanol preference in consecutive retention testing days, the effects of the administration of the kappa opioid antagonist MR-2266-BS, prior to or after the forced ethanol session, were studied. Pre-conditioning subcutaneous (s.c.) administration of 1 mg/kg of MR-2266-BS induced a decrease in subsequent ethanol consumption without significantly modifying the acquisition of ethanol preference. Post-conditioning administration of MR-2266-BS induced both a dose-dependent reduction in ethanol consumption and in preference throughout the three following days. The results of the present study provide further support of the involvement of kappa-type opioids on drinking behavior, and suggest that kappa receptors may be involved in the consumption and development of preference to ethanol.

Protective effect of N-Acetylcysteine against ethanol-induced gastric ulcer: a pharmacological assessment in mice

Directory of Open Access Journals (Sweden)

Ausama Ayoob Jaccob

2015-06-01

Aim: Since there is an increasing need for gastric ulcer therapies with optimum benefit-risk profile. This study was conducted to investigate gastro-protective effects of N-Acetylcysteine (NAC against ethanol-induced gastric ulcer models in mice. Materials and Methods: Forty-two mice were allocated into six groups consisting of 7 mice each. Groups 1 (normal control and 2 (ulcer control received distilled water at a dose of 10 ml/kg, groups 3, 4 and 5 were given NAC at doses 100, 300 and 500 mg/kg, respectively, and the 6th group received ranitidine (50 mg/kg. All drugs administered orally once daily for 7 days, on the 8th day absolute ethanol (7 ml/kg was administrated orally to all mice to induce the acute ulcer except normal control group. Then 3 h after, all animals were sacrificed then consequently the stomachs were excised for examination. Results: NAC administration at the tested doses showed a dose-related potent gastro-protective effect with significant increase in curative ratio, PH of gastric juice and mucus content viscosity seen with the highest dose of NAC and it is comparable with that observed in ranitidine group. Conclusion: The present findings demonstrate that, oral NAC shows significant gastro-protective effects comparable to ranitidine confirmed by antisecretory, cytoprotective, histological and biochemical data but the molecular mechanisms behind such protection are complex. [J Intercult Ethnopharmacol 2015; 4(2.000: 90-95

Antibacterial Activity and Mode of Action of Mentha arvensis Ethanol ...

African Journals Online (AJOL)

Antibacterial Activity and Mode of Action of Mentha arvensis Ethanol Extract against ... the antibacterial effect of ethanol extract of Mentha arvensis against multi-drug ... Reactive oxygen species (ROS) generation and protein leakage from the ... A. baumannii and acts by inducing lethal cellular damage to the bacterium.

Consequences of adolescent ethanol exposure in male Sprague-Dawley rats on fear conditioning and extinction in adulthood

Science.gov (United States)

Broadwater, Margaret A.

Some evidence suggests that adolescents are more vulnerable than adults to alcohol-induced cognitive deficits and that these deficits may persist into adulthood. Five experiments were conducted to assess long-term consequences of ethanol exposure on tone and context Pavlovian fear conditioning in male Sprague-Dawley rats. Experiment 1 examined age-related differences in sensitivity to ethanol-induced disruptions of fear conditioning to a pre-conditioning ethanol challenge. Experiments 2 examined fear conditioning 22 days after early-mid adolescent (P28-48) or adult (P70-90) exposure to 4 g/kg i.g. ethanol or water given every other day (total of 11 exposures). In Experiment 3, mid-late adolescents (P35-55) were exposed in the same manner to assess whether timing of ethanol exposure within the adolescent period would differentially affect later fear conditioning. Experiment 4 assessed the influence of prior adolescent or adult ethanol exposure on the disrupting effects of a pre-conditioning ethanol challenge. In Experiment 5, neurogenesis (doublecortin---DCX) and cholinergic (choline acetyltransferase---ChAT) markers were measured to assess potential long-term ethanol-induced changes in neural mechanisms important for learning and memory. Results indicated that the long-lasting behavioral effects of ethanol exposure varied depending on exposure age, with early-mid adolescent exposed animals showing attenuated context fear retention (a relatively hippocampal-dependent task), whereas mid-late adolescent and adult exposed animals showed slower context extinction (thought to be reliant on the mPFC). Early-mid adolescent ethanol-exposed animals also had significantly less DCX and ChAT expression than their water-exposed counterparts, possibly contributing to deficits in context fear. Tone fear was not influenced by prior ethanol exposure at any age. In terms of age differences in ethanol sensitivity, adolescents were less sensitive than adults to ethanol-induced

Olive (Olea europaea) leaf methanolic extract prevents HCl/ethanol-induced gastritis in rats by attenuating inflammation and augmenting antioxidant enzyme activities.

Science.gov (United States)

Al-Quraishy, Saleh; Othman, Mohamed S; Dkhil, Mohamed A; Abdel Moneim, Ahmed Esmat

2017-07-01

Gastritis is preponderantly characterized by inflammation of the lining epithelial layer and the chronic gastritis is considered as a pre-cancer lesion. For many centuries olive (Olea europaea) leaf has been used for its putative health potential, nonetheless, to date, the gastroprotective effects of olive leaves have not been studied yet. Hence, in this study we investigated whether olive leaf extract (OLE) could protect gastric mucosa against HCl/ethanol-induced gastric mucosal damage in rats. Hcl/ethanol administration caused significant damage to the gastric mucosa, as confirmed by gastric ulcer index and histological evaluation. However, this damage was largely prevented by pre-administering 20mg/kg omeprazole or 100mg/kg OLE. Interestingly, the damage was completely prevented by pre-administering 200 and 300mg/kg OLE. Moreover, OLE attenuated the inflammatory response by decreasing nuclear factor-κB (NF-κB), cycloxygenase-2 (COX-2) and tumor necrosis factor-α (TNF-α) expressions, and down-regulating inducible nitric oxide synthase (iNOS) and interleukin-1β (IL-1β) in gastric mucosa. The gastroprotective mechanism of OLE involved the promotion of enzymatic and nonenzymatic molecules (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione reduced form), promoting nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA expression, halting lipid peroxidation and preventing the overproduction of nitric oxide. Together, our findings clearly demonstrated that OLE could prevent HCl/ethanol-induced gastritis by attenuating inflammation and oxidant/antioxidant imbalance. Indeed, OLE could potentially be useful as a natural therapy for gastritis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Effect of mechanical vs dilute ethanol epithelial removal on keratocyte apoptosis and polymorphonuclear leukocyte migration.

Science.gov (United States)

Gurelik, G; Bilgihan, K; Sezer, C; Akyol, G; Hasanreisoglu, B

2002-03-01

To investigate keratocyte apoptosis and polymorphonuclear (PMN) cell infiltration to the corneal stroma after mechanical epithelial scraping and chemical de-epithelialization with 18% ethanol solution. Twelve New Zealand Albino rabbits (24 eyes) were randomly divided into three groups. Group A was the control group with no epithelial removal. Group B underwent a 7.5-mm mechanical epithelial removal with a blunt spatula. Group C underwent 7.5-mm chemical de-epithelialization with 18% ethanol-balanced salt solution. Corneas were stained with terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick-end labeling (TUNEL) assay after 24 h. Only nuclear staining in keratocytes was counted. Polymorphonuclear (PMN) leukocyte densities were also assessed by light microscopy. Mechanical de-epithelialization (group B) and chemical de-epithelialization with 18% ethanol (group C) showed no difference in keratocyte apoptosis compared with the control group. There was also no difference between groups B and C. Group B showed no difference in PMN leukocyte counts compared with the control group. But the number of PMN leukocytes observed in group C was significantly higher than those encountered in the corneas of the control group (P < 0.05) and group B (P < 0.05). Dilute alcohol induces more PMN cell infiltration when compared with mechanical de-epithelialization although there is no difference in the apoptosis rates.

In vivo anti-arthritic and anti-nociceptive effects of ethanol extract of Moringa oleifera leaves on complete Freund's adjuvant (CFA)-induced arthritis in rats.

Science.gov (United States)

Mahdi, Harith Jameel; Khan, Nurzalina Abdul Karim; Asmawi, Mohd Zaini Bin; Mahmud, Roziahanim; A/L Murugaiyah, Vikneswaran

2018-03-01

The medicinal uses of plants are in many cases based exclusively on traditional knowledge without enough scientific evidences. Different parts of Moringa oleifera were traditionally used for the treatment of wide variety of ailments including arthritis and joints pain. The present study had been designed to evaluate the anti-arthritic and anti-nociceptive activities of ethanol extract of Moringa leaves, this being the most abundant plant part suitable for commercial mass production of botanical medicinal products. Complete Freund's adjuvant (CFA)-induced arthritis in rats was used as disease model. CFA-induced inflammatory paw edema, body weight, arthritic index, X-ray radiography, hematological parameters, and walk track and locomotion analysis were all evaluated for the assessment of disease progression. In addition to that, anti-nociceptive activity was examined at different dose levels in both normal and arthritic-induced rats using Eddy's hot plate and tail flick thermal analgesia. The analysis of various arthritic assessment parameters used in this study revealed that Moringa extract has a considerable effect in preventing development or ameliorate arthritis disease severity. Moreover, the ethanol extract of Moringa leaves revealed significant anti-nociceptive activity at in both normal and CFA-induced arthritis rats in a dose-dependent manner. Ethanol extract of Moringa leaves appears to be a really promising as analgesic and arthritis medication, but a larger and more detailed preclinical and clinical studies especially in human is highly recommended.

Contrast Induced by a Static Magnetic Field for Improved Detection in Nanodiamond Fluorescence Microscopy

Science.gov (United States)

Singam, Shashi K. R.; Motylewski, Jaroslaw; Monaco, Antonina; Gjorgievska, Elena; Bourgeois, Emilie; Nesládek, Milos; Giugliano, Michele; Goovaerts, Etienne

2016-12-01

Diamond nanoparticles with negatively charged nitrogen-vacancy (NV) centers are highly efficient nonblinking emitters that exhibit spin-dependent intensity. An attractive application of these emitters is background-free fluorescence microscopy exploiting the fluorescence quenching induced either by resonant microwaves (RMWs) or by an applied static magnetic field (SMF). Here, we compare RMW- and SMF-induced contrast measurements over a wide range of optical excitation rates for fluorescent nanodiamonds (FNDs) and for NV centers shallowly buried under the (100)-oriented surface of a diamond single crystal (SC). Contrast levels are found to be systematically lower in the FNDs than in the SC. At low excitation rates, the RMW contrast initially rises to a maximum (up to 7% in FNDs and 13% in the SC) but then decreases steadily at higher intensities. Conversely, the SMF contrast increases from approximately 12% at low excitation rates to high values of 20% and 38% for the FNDs and SC, respectively. These observations are well described in a rate-equations model for the charged NV defect using parameters in good agreement with the literature. The SMF approach yields higher induced contrast in image collection under commonly applied optical excitation. Unlike the RMW method, there is no thermal load exerted on the aqueous media in biological samples in the SMF approach. We demonstrate imaging by SMF-induced contrast in neuronal cultures incorporating FNDs (i) in a setup for patch-clamp experiments in parallel with differential-interference-contrast microscopy, (ii) after a commonly used staining procedure as an illustration of the high selectivity against background fluorescence, and (iii) in a confocal fluorescence microscope in combination with bright-field microscopy.

Mechanistic insight into ultrasound induced enhancement of simultaneous saccharification and fermentation of Parthenium hysterophorus for ethanol production.

Science.gov (United States)

Singh, Shuchi; Agarwal, Mayank; Sarma, Shyamali; Goyal, Arun; Moholkar, Vijayanand S

2015-09-01

This paper presents investigations into mechanism of ultrasound assisted bioethanol synthesis using Parthenium hysterophorus biomass through simultaneous saccharification and fermentation (SSF) mode. Approach of coupling experimental results to mathematical model for SSF using Genetic Algorithm based optimization has been adopted. Comparison of model parameters for experiments with mechanical shaking and sonication (10% duty cycle) give an interesting mechanistic account of influence of ultrasound on SSF system. A 4-fold rise in ethanol and cell mass productivity is seen with ultrasound. The analysis reveals following facets of influence of ultrasound on SSF: increase in Monod constant for glucose for cell growth, maximal specific growth rate and inhibition constant of cell growth by glucose and reduction in specific cell death rate. Values of inhibition constant of cell growth by ethanol (K3E), and constants for growth associated (a) and non-growth associated (b) ethanol production remained unaltered with sonication. Beneficial effects of ultrasound are attributed to enhanced cellulose hydrolysis, enhanced trans-membrane transport of substrate and products as well as dilution of the toxic substances due to micro-convection induced by ultrasound. Intrinsic physiological functioning of cells remained unaffected by ultrasound as indicated by unaltered values of K3E, a and b. Copyright © 2015 Elsevier B.V. All rights reserved.

Resveratrol suppresses ethanol stress in winery and bottom brewery yeast by affecting superoxide dismutase, lipid peroxidation and fatty acid profile.

Science.gov (United States)

Gharwalova, Lucia; Sigler, Karel; Dolezalova, Jana; Masak, Jan; Rezanka, Tomas; Kolouchova, Irena

2017-11-03

Mid-exponential cultures of two traditional biotechnological yeast species, winery Saccharomyces cerevisiae and the less ethanol tolerant bottom-fermenting brewery Saccharomyces pastorianus, were exposed to different concentrations of added ethanol (3, 5 and 8%) The degree of ethanol-induced cell stress was assessed by measuring the cellular activity of superoxide dismutase (SOD), level of lipid peroxidation products, changes in cell lipid content and fatty acid profile. The resveratrol as an antioxidant was found to decrease the ethanol-induced rise of SOD activity and suppress the ethanol-induced decrease in cell lipids. A lower resveratrol concentration (0.5 mg/l) even reduced the extent of lipid peroxidation in cells. Resveratrol also alleviated ethanol-induced changes in cell lipid composition in both species by strongly enhancing the proportion of saturated fatty acids and contributing thereby to membrane stabilization. Lower resveratrol concentrations could thus diminish the negative effects of ethanol stress on yeast cells and improve their physiological state. These effects may be utilized to enhance yeast vitality in high-ethanol-producing fermentations or to increase the number of yeast generations in brewery.

Ethanol adsorption on the {10(1)over-bar4} calcite surface

DEFF Research Database (Denmark)

Sand, Karina Krarup; Stipp, Susan Louise Svane; Hassenkam, Tue

2008-01-01

Preliminary atomic force microscopy investigations of the {10 (1) over bar4} calcite Surface cleaved in ethanol indicate a different surface behaviour than that of the {10 (1) over bar4} surface cleaved in air. The results are consistent with recent theoretical studies and suggest strong ordering...

Development of a new light collection and detection system optimized for ion beam induced fluorescence microscopy

International Nuclear Information System (INIS)

Vanga, Sudheer Kumar; Mi, Zhaohong; Koh, Long Cheng; Tao, Ye; Bettiol, Andrew A.; Watt, Frank

2015-01-01

Ion beam induced fluorescence microscopy is a new imaging technique which has the potential to achieve sub-50 nm spatial resolution fluorescence images. Currently the resolution of the technique has been limited to around 150 nm mainly because of inefficient collection and detection of emitted photons from the sample. To overcome this limitation, a new light collection system based on a custom made parabolic mirror is employed to enhance the fluorescence collection. The custom made mirror is designed so as to obtain both structural (scanning transmission ion microscopy) and ion beam induced fluorescence imaging simultaneously. The design and characterization of the parabolic mirror is discussed in detail

The effects of gonadectomy and binge-like ethanol exposure during adolescence on open field behaviour in adult male rats.

Science.gov (United States)

Yan, Wensheng; Kang, Jie; Zhang, Guoliang; Li, Shuangcheng; Kang, Yunxiao; Wang, Lei; Shi, Geming

2015-09-14

Binge drinking ethanol exposure during adolescence can lead to long-term neurobehavioural damage. It is not known whether the pubertal surge in testosterone that occurs during adolescence might impact the neurobehavioural effects of early ethanol exposure in adult animals. We examined this hypothesis by performing sham or gonadectomy surgeries on Sprague-Dawley rats around postnatal day (P) 23. From P28-65,the rats were administered 3.0g/kg ethanol using a binge-like model of exposure. Dependent measurements included tests of open field behaviour, blood ethanol concentrations, and testosterone levels. As adults, significant decreases in open field activity were observed in the GX rats. The open field behaviour of the GX rats was restored after testosterone administration. Binge-like ethanol exposure altered most of the parameters of the open field behaviour, suggestive of alcohol-induced anxiety, but rats treated with alcohol in combination with gonadectomy showed less motor behaviour and grooming behaviour and an increase in immobility, suggesting ethanol-induced depression. These results indicated that testosterone is required for ethanol-induced behavioural changes and that testicular hormones are potent stimulators of ethanol-induced behaviours. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Highly Ordered Periodic Au/TiO₂ Hetero-Nanostructures for Plasmon-Induced Enhancement of the Activity and Stability for Ethanol Electro-oxidation.

Science.gov (United States)

Jin, Zhao; Wang, Qiyu; Zheng, Weitao; Cui, Xiaoqiang

2016-03-02

The catalytic electro-oxidation of ethanol is the essential technique for direct alcohol fuel cells (DAFCs) in the area of alternative energy for the ability of converting the chemical energy of alcohol into the electric energy directly. Developing highly efficient and stable electrode materials with antipoisoning ability for ethanol electro-oxidation remains a challenge. A highly ordered periodic Au-nanoparticle (NP)-decorated bilayer TiO2 nanotube (BTNT) heteronanostructure was fabricated by a two-step anodic oxidation of Ti foil and the subsequent photoreduction of HAuCl4. The plasmon-induced charge separation on the heterointerface of Au/TiO2 electrode enhances the electrocatalytic activity and stability for the ethanol oxidation under visible light irradiation. The highly ordered periodic heterostructure on the electrode surface enhanced the light harvesting and led to the greater performance of ethanol electro-oxidation under irradiation compared with the ordinary Au NPs-decorated monolayer TiO2 nanotube (MTNT). This novel Au/TiO2 electrode also performed a self-cleaning property under visible light attributed to the enhanced electro-oxidation of the adsorbed intermediates. This light-driven enhancement of the electrochemical performances provides a development strategy for the design and construction of DAFCs.

The tendency to sign-track predicts cue-induced reinstatement during nicotine self-administration, and is enhanced by nicotine but not ethanol

Science.gov (United States)

Versaggi, Cassandra L.; King, Christopher P.; Meyer, Paul J.

2016-01-01

Rationale Some individuals are particularly responsive to reward-associated stimuli (“cues”), including the effects of these cues on craving and relapse to drug-seeking behavior. In the cases of nicotine and alcohol, cues may acquire these abilities via the incentive-enhancing properties of the drug. Objectives To determine the interaction between cue-responsivity and nicotine reinforcement, we studied the patterns of nicotine self-administration in rats categorized based on their tendency to approach a food predictive cue (“sign-trackers”) or a reward-delivery location (“goal-trackers”). In a second experiment, we determined whether nicotine and ethanol altered the incentive value of a food cue. Methods Rats were classified as sign- or goal-trackers during a Pavlovian conditioned approach paradigm. Rats then self-administered intravenous nicotine (0.03 mg/kg infusions) followed by extinction and cue induced reinstatement tests. We also tested the effects of nicotine (0.4 mg/kg base s.c.) or ethanol (0.7 g/kg i.p.) on the approach to, and reinforcing efficacy of, a food cue. Results Sign-trackers showed greater reinstatement in response to a nicotine cue. Further, nicotine enhanced sign-tracking but not goal-tracking to a food cue, and also enhanced responding for the food cue during the conditioned reinforcement test. Conversely, ethanol reduced sign-tracking and increased goal-tracking, but had no effect on conditioned reinforcement. Conclusions Our studies demonstrate that the tendency to attribute incentive value to a food cue predicts enhanced cue-induced reinstatement. Additionally, the incentive value of food cues is differentially modulated by nicotine and ethanol, which may be related to the reinforcing effects of these drugs. PMID:27282365

The tendency to sign-track predicts cue-induced reinstatement during nicotine self-administration, and is enhanced by nicotine but not ethanol.

Science.gov (United States)

Versaggi, Cassandra L; King, Christopher P; Meyer, Paul J

2016-08-01

Some individuals are particularly responsive to reward-associated stimuli ("cues"), including the effects of these cues on craving and relapse to drug-seeking behavior. In the cases of nicotine and alcohol, cues may acquire these abilities via the incentive-enhancing properties of the drug. To determine the interaction between cue-responsivity and nicotine reinforcement, we studied the patterns of nicotine self-administration in rats categorized based on their tendency to approach a food-predictive cue ("sign-trackers") or a reward-delivery location ("goal-trackers"). In a second experiment, we determined whether nicotine and ethanol altered the incentive value of a food cue. Rats were classified as sign- or goal-trackers during a Pavlovian conditioned approach paradigm. Rats then self-administered intravenous nicotine (0.03 mg/kg infusions) followed by extinction and cue-induced reinstatement tests. We also tested the effects of nicotine (0.4 mg/kg base s.c.) or ethanol (0.7 g/kg i.p.) on the approach to, and reinforcing efficacy of, a food cue. Sign-trackers showed greater reinstatement in response to a nicotine cue. Further, nicotine enhanced sign-tracking but not goal-tracking to a food cue and also enhanced responding for the food cue during the conditioned reinforcement test. Conversely, ethanol reduced sign-tracking and increased goal-tracking, but had no effect on conditioned reinforcement. Our studies demonstrate that the tendency to attribute incentive value to a food cue predicts enhanced cue-induced reinstatement. Additionally, the incentive value of food cues is differentially modulated by nicotine and ethanol, which may be related to the reinforcing effects of these drugs.

Preparation and electrocatalytic properties of Pt-SiO2 nanocatalysts for ethanol electrooxidation.

Science.gov (United States)

Liu, B; Chen, J H; Zhong, X X; Cui, K Z; Zhou, H H; Kuang, Y F

2007-03-01

Due to their high stability in general acidic solutions, SiO(2) nanoparticles were selected as the second catalyst for ethanol oxidation in sulfuric acid aqueous solution. Pt-SiO(2) nanocatalysts were prepared in this paper. The micrography and elemental composition of Pt-SiO(2) nanoparticles were characterized by scanning electron microscopy and energy dispersive X-ray spectroscopy, respectively. The electrocatalytic properties of Pt-SiO(2) nanocatalysts for ethanol oxidation were investigated by cyclic voltammetry. Under the same Pt loading mass and experimental conditions for ethanol oxidation, Pt-SiO(2) nanocatalysts show higher activity than PtRu/C (E-Tek), Pt/C (E-Tek), and Pt catalysts. Additionally, Pt-SiO(2) nanocatalysts possess good anti-poisoning ability. The results indicate that Pt-SiO(2) nanocatalysts may have good potential applications in direct ethanol fuel cells.

GABAA Receptors Containing ρ1 Subunits Contribute to In Vivo Effects of Ethanol in Mice

Science.gov (United States)

Blednov, Yuri A.; Benavidez, Jillian M.; Black, Mendy; Leiter, Courtney R.; Osterndorff-Kahanek, Elizabeth; Johnson, David; Borghese, Cecilia M.; Hanrahan, Jane R.; Johnston, Graham A. R.; Chebib, Mary; Harris, R. Adron

2014-01-01

GABAA receptors consisting of ρ1, ρ2, or ρ3 subunits in homo- or hetero-pentamers have been studied mainly in retina but are detected in many brain regions. Receptors formed from ρ1 are inhibited by low ethanol concentrations, and family-based association analyses have linked ρ subunit genes with alcohol dependence. We determined if genetic deletion of ρ1 in mice altered in vivo ethanol effects. Null mutant male mice showed reduced ethanol consumption and preference in a two-bottle choice test with no differences in preference for saccharin or quinine. Null mutant mice of both sexes demonstrated longer duration of ethanol-induced loss of righting reflex (LORR), and males were more sensitive to ethanol-induced motor sedation. In contrast, ρ1 null mice showed faster recovery from acute motor incoordination produced by ethanol. Null mutant females were less sensitive to ethanol-induced development of conditioned taste aversion. Measurement of mRNA levels in cerebellum showed that deletion of ρ1 did not change expression of ρ2, α2, or α6 GABAA receptor subunits. (S)-4-amino-cyclopent-1-enyl butylphosphinic acid (“ρ1” antagonist), when administered to wild type mice, mimicked the changes that ethanol induced in ρ1 null mice (LORR and rotarod tests), but the ρ1 antagonist did not produce these effects in ρ1 null mice. In contrast, (R)-4-amino-cyclopent-1-enyl butylphosphinic acid (“ρ2” antagonist) did not change ethanol actions in wild type but produced effects in mice lacking ρ1 that were opposite of the effects of deleting (or inhibiting) ρ1. These results suggest that ρ1 has a predominant role in two in vivo effects of ethanol, and a role for ρ2 may be revealed when ρ1 is deleted. We also found that ethanol produces similar inhibition of function of recombinant ρ1 and ρ2 receptors. These data indicate that ethanol action on GABAA receptors containing ρ1/ρ2 subunits may be important for specific effects of ethanol in vivo. PMID:24454882

GABAA receptors containing ρ1 subunits contribute to in vivo effects of ethanol in mice.

Directory of Open Access Journals (Sweden)

Yuri A Blednov

Full Text Available GABAA receptors consisting of ρ1, ρ2, or ρ3 subunits in homo- or hetero-pentamers have been studied mainly in retina but are detected in many brain regions. Receptors formed from ρ1 are inhibited by low ethanol concentrations, and family-based association analyses have linked ρ subunit genes with alcohol dependence. We determined if genetic deletion of ρ1 in mice altered in vivo ethanol effects. Null mutant male mice showed reduced ethanol consumption and preference in a two-bottle choice test with no differences in preference for saccharin or quinine. Null mutant mice of both sexes demonstrated longer duration of ethanol-induced loss of righting reflex (LORR, and males were more sensitive to ethanol-induced motor sedation. In contrast, ρ1 null mice showed faster recovery from acute motor incoordination produced by ethanol. Null mutant females were less sensitive to ethanol-induced development of conditioned taste aversion. Measurement of mRNA levels in cerebellum showed that deletion of ρ1 did not change expression of ρ2, α2, or α6 GABAA receptor subunits. (S-4-amino-cyclopent-1-enyl butylphosphinic acid ("ρ1" antagonist, when administered to wild type mice, mimicked the changes that ethanol induced in ρ1 null mice (LORR and rotarod tests, but the ρ1 antagonist did not produce these effects in ρ1 null mice. In contrast, (R-4-amino-cyclopent-1-enyl butylphosphinic acid ("ρ2" antagonist did not change ethanol actions in wild type but produced effects in mice lacking ρ1 that were opposite of the effects of deleting (or inhibiting ρ1. These results suggest that ρ1 has a predominant role in two in vivo effects of ethanol, and a role for ρ2 may be revealed when ρ1 is deleted. We also found that ethanol produces similar inhibition of function of recombinant ρ1 and ρ2 receptors. These data indicate that ethanol action on GABAA receptors containing ρ1/ρ2 subunits may be important for specific effects of ethanol in vivo.

Chronic ethanol feeding modulates the synthesis of digestive enzymes

International Nuclear Information System (INIS)

Ponnappa, B.C.; Hoek, J.B.; Rubin, E.

1987-01-01

The effects of chronic ethanol feeding on pancreatic protein synthesis were investigated. Protein synthesis was assessed by studying the rate of incorporation of 3 H-leucine into TCA-precipitable proteins in isolated pancreatic acini from rats. Chronic ethanol ingestion increased the rate of pancreatic protein synthesis by 2-4 fold. The onset of the increase in protein synthesis was detectable two days after ethanol feeding, reached a maximum after 7 days and remained unchanged after 4 months on the ethanol-containing diet. The rate of synthesis of individual digestive enzymes was studied by SDS-PAGE on extracts obtained from purified zymogen granules. Ethanol feeding induced an increase in the rate of synthesis of most of the digestive enzymes; chymotrypsinogen, trypsinogen and an unidentified protein were increased to a greater extent than other digestive enzymes. By contrast, the synthesis of amylase was selectively decreased after ethanol feeding. These results suggest that chronic ethanol ingestion has specific effects on the rate of synthesis of individual digestive enzymes in the exocrine pancreas

The highly selective orexin/hypocretin 1 receptor antagonist GSK1059865 potently reduces ethanol drinking in ethanol dependent mice.

Science.gov (United States)

Lopez, Marcelo F; Moorman, David E; Aston-Jones, Gary; Becker, Howard C

2016-04-01

The orexin/hypocretin (ORX) system plays a major role in motivation for natural and drug rewards. In particular, a number of studies have shown that ORX signaling through the orexin 1 receptor (OX1R) regulates alcohol seeking and consumption. Despite the association between ORX signaling and motivation for alcohol, no study to date has investigated what role the ORX system plays in alcohol dependence, an understanding of which would have significant clinical relevance. This study was designed to evaluate the effect of the highly selective OX1R antagonist GSK1059865 on voluntary ethanol intake in ethanol-dependent and control non-dependent mice. Mice were subjected to a protocol in which they were evaluated for baseline ethanol intake and then exposed to intermittent ethanol or air exposure in inhalation chambers. Each cycle of chronic intermittent ethanol (CIE), or air, exposure was followed by a test of ethanol intake. Once the expected effect of increased voluntary ethanol intake was obtained in ethanol dependent mice, mice were tested for the effect of GSK1059865 on ethanol and sucrose intake. Treatment with GSK1059865 significantly decreased ethanol drinking in a dose-dependent manner in CIE-exposed mice. In contrast GSK1059865 decreased drinking in air-exposed mice only at the highest dose used. There was no effect of GSK1059865 on sucrose intake. Thus, ORX signaling through the OX1R, using a highly-selective antagonist, has a profound influence on high levels of alcohol drinking induced in a dependence paradigm, but limited or no influence on moderate alcohol drinking or sucrose drinking. These results indicate that the ORX system may be an important target system for treating disorders of compulsive reward seeking such as alcoholism and other addictions in which motivation is strongly elevated. Copyright © 2016 Elsevier B.V. All rights reserved.

T1r3 taste receptor involvement in gustatory neural responses to ethanol and oral ethanol preference.

Science.gov (United States)

Brasser, Susan M; Norman, Meghan B; Lemon, Christian H

2010-05-01

Elevated alcohol consumption is associated with enhanced preference for sweet substances across species and may be mediated by oral alcohol-induced activation of neurobiological substrates for sweet taste. Here, we directly examined the contribution of the T1r3 receptor protein, important for sweet taste detection in mammals, to ethanol intake and preference and the neural processing of ethanol taste by measuring behavioral and central neurophysiological responses to oral alcohol in T1r3 receptor-deficient mice and their C57BL/6J background strain. T1r3 knockout and wild-type mice were tested in behavioral preference assays for long-term voluntary intake of a broad concentration range of ethanol, sucrose, and quinine. For neurophysiological experiments, separate groups of mice of each genotype were anesthetized, and taste responses to ethanol and stimuli of different taste qualities were electrophysiologically recorded from gustatory neurons in the nucleus of the solitary tract. Mice lacking the T1r3 receptor were behaviorally indifferent to alcohol (i.e., ∼50% preference values) at concentrations typically preferred by wild-type mice (5-15%). Central neural taste responses to ethanol in T1r3-deficient mice were significantly lower compared with C57BL/6J controls, a strain for which oral ethanol stimulation produced a concentration-dependent activation of sweet-responsive NTS gustatory neurons. An attenuated difference in ethanol preference between knockouts and controls at concentrations >15% indicated that other sensory and/or postingestive effects of ethanol compete with sweet taste input at high concentrations. As expected, T1r3 knockouts exhibited strongly suppressed behavioral and neural taste responses to sweeteners but did not differ from wild-type mice in responses to prototypic salt, acid, or bitter stimuli. These data implicate the T1r3 receptor in the sensory detection and transduction of ethanol taste.

Anticonvulsant activity of the ethanolic extract of Punica granatum L. seed.

Science.gov (United States)

Mehrzadi, Saeed; Sadr, Samir; Hosseinzadeh, Azam; Gholamine, Babak; Shahbazi, Ali; FallahHuseini, Hasan; Ghaznavi, Habib

2015-06-01

Various morphological parts of pomegranate (Punica granatum L.) have extensively been used in the folk medicine to treat an array of human ailments. The aim of the present study is to demonstrate the anticonvulsant potential of the ethanolic extract of P. granatum L. seed in chemoconvulsant-induced seizures in mice. The anticonvulsant activity of the ethanolic extract was investigated in strychnine (STR)-induced and pentylenetetrazole (PTZ)-induced seizure models in mice. Diazepam was used as reference anticonvulsant drug. Ethanolic extract (150, 300, and 600 mg/kg per os, p.o.), diazepam (1 mg/kg intraperitoneally, i.p.), and distilled water (10 ml/kg, i.p.) were administered before induction of seizures by PTZ (60 mg/kg, i.p.) or STR (2.5 mg/kg, i.p.). The latent time before the onset of convulsions, the duration of convulsions, the percentage of seizure protection, and mortality rate were recorded. The seed ethanolic extract did not show any toxicity and did not protect the animals against seizures but demonstrated a significant increase in seizure latency at 300 and 600 mg/kg in both STR and PTZ seizure models (P < 0.001). It also showed a significant reduction in seizure duration at 300 mg/kg (P < 0.05) and 600 mg/kg (P < 0.001) in the STR seizure model and 600 mg/kg (P < 0.01) in the PTZ seizure model compared with the control group. Ethanol extract has dose-dependent anticonvulsant activity against STR- and PTZ-induced seizures. This activity might be due to its saponins, flavonoids, triterpenes, and alkaloids ingredients.

Supersensitive Kappa Opioid Receptors Promotes Ethanol Withdrawal-Related Behaviors and Reduce Dopamine Signaling in the Nucleus Accumbens.

Science.gov (United States)

Rose, Jamie H; Karkhanis, Anushree N; Chen, Rong; Gioia, Dominic; Lopez, Marcelo F; Becker, Howard C; McCool, Brian A; Jones, Sara R

2016-05-01

Chronic ethanol exposure reduces dopamine transmission in the nucleus accumbens, which may contribute to the negative affective symptoms associated with ethanol withdrawal. Kappa opioid receptors have been implicated in withdrawal-induced excessive drinking and anxiety-like behaviors and are known to inhibit dopamine release in the nucleus accumbens. The effects of chronic ethanol exposure on kappa opioid receptor-mediated changes in dopamine transmission at the level of the dopamine terminal and withdrawal-related behaviors were examined. Five weeks of chronic intermittent ethanol exposure in male C57BL/6 mice were used to examine the role of kappa opioid receptors in chronic ethanol-induced increases in ethanol intake and marble burying, a measure of anxiety/compulsive-like behavior. Drinking and marble burying were evaluated before and after chronic intermittent ethanol exposure, with and without kappa opioid receptor blockade by nor-binaltorphimine (10mg/kg i.p.). Functional alterations in kappa opioid receptors were assessed using fast scan cyclic voltammetry in brain slices containing the nucleus accumbens. Chronic intermittent ethanol-exposed mice showed increased ethanol drinking and marble burying compared with controls, which was attenuated with kappa opioid receptor blockade. Chronic intermittent ethanol-induced increases in behavior were replicated with kappa opioid receptor activation in naïve mice. Fast scan cyclic voltammetry revealed that chronic intermittent ethanol reduced accumbal dopamine release and increased uptake rates, promoting a hypodopaminergic state of this region. Kappa opioid receptor activation with U50,488H concentration-dependently decreased dopamine release in both groups; however, this effect was greater in chronic intermittent ethanol-treated mice, indicating kappa opioid receptor supersensitivity in this group. These data suggest that the chronic intermittent ethanol-induced increase in ethanol intake and anxiety