Protective Effect Of Ethanol Research Articles

The effects of traditional fermented beverages on ethanol, ethyl glucuronide and ethyl sulphate levels

BackgroundTraditional beverages such as şalgam, boza, kımız and kefir are frequently being consumed in Turkey. During the production of these beverages fermentation provides long time bio-preservation due to protective effects of ethanol, a product of microorganisms’ metabolism. Especially in traffic controls and in rehabilitation process of alcoholic patients, fermented beverages may cause confusion since it may be linked with false positivity of ethanol and ethanol metabolite tests. The present study aims to assess blood ethanol and urine ethanol metabolite levels after consumption of traditional fermented beverages.MethodTwelve participants consumed 300 mL standardized homemade traditional şalgam, boza, kımız and kefir. Blood samples were collected before and after (at 45th min) consumption and urine samples were collected before and after (at 4th hour) consumption from the participants. The samples of these four beverages and the blood samples were analyzed using headspace gas chromatography for ethanol levels, and urine samples were analyzed with liquid chromatography tandem mass spectrometry for ethyl-glucuronide and ethyl-sulphate levels.ResultsEthanol levels in şalgam, boza, kımız, and kefir samples, used at the present study, were 80.02 mg/dl, 30.02 mg/dl, 57.83 mg/dl and 6.07 mg/dl, respectively. After consumption of beverages, blood ethanol levels were negative for all analyzed samples. No statistically significant correlation was found between initial and post-consumption ethyl-glucuronide and ethyl-sulphate levels.

Possible protective effect of ethanol on acute methanol intoxicated retina in rats: A histological and ultrastructural study

Background: Methanol poisoning frequently occurs via oral ingestion of adulterated spirits as ethanol substitutes. Retina is particularly susceptible to the toxic effects of methanol. Ethanol is frequently used for treatment where prompt management is crucial to avoid irreversible ocular damage.Aim of the work: The aim of this work is to study the histological and ultrastructural effect of methanol intoxication on the retina, as well as the ability of ethanol to protect against methanol induced retinal damage.Materials and Methods: Thirty adult male albino rats, were used in the study. Rats were divided into three groups (n=10 per group): Group 1 (Control group); Group 2 (Methanol treated group) and Group 3 (Methanol + Ethanol treated group). Rats were sacrificed after 24 hours of methanol administration. Retinae were examined histologically and ultrastructurally.Results: Histological and ultrastructure examination of the retina of rats treated with methanol showed marked edema of all layers, disorganized nuclear layers and decreased number of ganglion cells. Electron microscopic examination revealed fragmented outer segment, disorganized inner segment. Administration of ethanol in methanol intoxicated rats resulted in preservation of retinal structure with marked attenuation of methanol induced retinal damage.Conclusions: Methanol poisoning induces damage of the retina. Administration of ethanol protects the retina and attenuates histopathological changes induced by methanol.

Protective effects of aqueous and ethanol extracts of rosemary on H2O2-induced oxidative DNA damage in human lymphocytes by comet assay

Rosemary (Rosmarinus officinalis) possesses various pharmacological properties such as antioxidant, anti-tumorigenesis and anti-mutagenesis activities. In this study, we investigated the possible protective effects of ethanol and aqueous extracts of rosemary on human lymphocyte DNA damage induced by H2O2. The extent of DNA lesions was measured using comet assay. Blood samples were taken from healthy volunteers and lymphocytes were isolated. The lymphocytes were then incubated in aqueous and ethanol extract of rosemary (0.05, 0.1, 0.5, 1 and 2.5 mg/mL) and H2O2 (50, 100 and 200 mM). Lymphocytes were also incubated with a combination of H2O2 (100 mM) with either 1 or 2.5 mg/mL of both extracts for 30 min at 4°C. Our findings showed that H2O2 treatment led to a significant concentrate-dependent DNA damage in human lymphocyte when compared to respective controls (p<0.001). The DNA damage which was initially occurred as the result of 100 µM H2O2 (Percentage tail DNA 55.1%) was inhibited due to the ethanol extract of rosemary at the doses tested (percentage tail DNA 4.7% and 4.03%). However, the aqueous extract has no effects on H2O2 genotoxicity. We suggest that antioxidant constituents in ethanol extract of rosemary can prevent human lymphocytes oxidative DNA damage which is due to its free radical scavenging activity.

Effects of ethanol on the properties of platelets and endothelial cells in model experiments

To investigate effects of ethanol on activity markers of atherosclerosis in an in vitro endothelial cell model. After 24 h incubation with ethanol (0.0095%), human umbilical vein endothelial cells were stimulated for 1 h with lipopolysaccharide, and were then incubated in direct contact with activated platelets. Following this incubation, the expression of CD40L and CD62P on platelets, and the expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), urokinase plasminogen activator receptor (uPAR), and membrane-type 1 matrix metalloproteinase (MT1-MMP) on endothelial cells were measured by flow cytometry. The increased expression of VCAM-1 and uPAR on endothelial cells by proinflammatory stimulation with activated platelets was significantly reduced through pre-incubation with ethanol (P < 0.05). Furthermore, platelets in direct contact with ethanol and with endothelial cells pre-incubated in ethanol showed a significant reduction in their CD40L expression (P < 0.05). Ethanol had no significant effect on ICAM-1 and MT1-MMP expression on endothelial cells. Ethanol directly attenuates platelet activation and has significant endothelial cell-mediated effects on selected markers of atherosclerosis in vitro. These findings underline possible protective effects of ethanol on atherosclerosis.

Neuroprotective Effect of Acute Ethanol Administration in a Rat With Transient Cerebral Ischemia

Ethanol consumption is inversely associated with the risk of ischemic stroke, suggesting a neuroprotective effect. In a rat model of transient cerebral ischemia, we identified ethanol as a possible treatment for acute ischemic stroke. Sprague-Dawley rats were subjected to middle cerebral artery occlusion for 2 hours. Five sets of experiments were conducted: to determine the dose-response effect of ethanol on brain infarction and functional outcome; to determine whether combining ethanol and hypothermia produces synergistic neuroprotection; to determine the therapeutic windows of opportunity for ethanol in stroke; to test whether ethanol promotes intracerebral hemorrhage in a hemorrhagic or ischemic stroke or after administration of thrombolytics; and to test the affect of ethanol on hypoxia-inducible factor-1α protein expression. Ethanol at 1.5 g/kg reduced infarct volume and behavioral dysfunction when administered at 2, 3, or 4 hours after middle cerebral artery occlusion. The protective effect of ethanol was not improved when paired with hypothermia. Ethanol did not promote cerebral hemorrhage in hemorrhagic or ischemic stroke in combination with recombinant tissue-type plasminogen activator or urokinase. Ethanol treatment (1.5 g/kg) increased protein levels of hypoxia-inducible factor-1α at 3 hours postreperfusion. Ethanol exerts a strong neuroprotective effect when administered up to 4 hours after ischemia, increases expression of hypoxia-inducible factor-1α, and does not promote intracerebral hemorrhage when used with thrombolytics. Ethanol is a potential neuroprotectant for acute ischemic stroke.

The frequency of daily ethanol consumption influences the effect of ethanol on insulin sensitivity in rats fed a high-fat diet

The different effects of ethanol on insulin sensitivity may be due to complex reasons. Here, we focus on the various daily ethanol consumption frequencies in rats fed a high-fat (HF) diet and explore the possible mechanism mediated by adiponectin and AMP-activated protein kinase (AMPK). A total of thirty-six male Wistar rats were fed a HF diet and were randomly divided into three groups: those that received tap water (C); those that received ethanol via a gastric tube twice per d (E1); those that received free access to ethanol for drinking (E2). The total daily ethanol dosage in groups E1 and E2 were the same (5 g/kg per d). At the end of 18 weeks, insulin sensitivity was evaluated. Adiponectin AMPK and GLUT4 levels were determined. We found that the different administration frequencies led to markedly different plasma ethanol concentrations and there were intimate relationships between plasma ethanol concentration and insulin sensitivity. Insulin resistance was markedly improved in group E1, whereas only a slight improvement was observed in group E2. Accordingly, adiponectin, phosphorylated AMPK and GLUT4 levels were significantly increased in group E1. Based on these findings, we propose that ethanol concentration might be the major influencing factor mediating the effect of ethanol on insulin sensitivity. At a total daily dosage of 5 g/kg per d, twice daily administration of ethanol was more beneficial than continuous drinking. The protective effect of ethanol might be mediated by increased adiponectin levels, which subsequently improve the activation of AMPKα and GLUT4 expression in adipose tissue.

Ethanol preconditioning prevents ischemia‐reperfusion‐induced mitochondrial dysfunction in intestinal mucosa by an adenosine‐dependent mechanism in rats

Ethanol preconditioning (EPC) protects tissues from ischemia‐reperfusion (IR)‐induced injury by an unknown mechanism. Whereas ischemic preconditioning prevents IR‐induced mitochondrial dysfunction, it is unknown whether EPC has a similar protective effect. We tested this question in rats subjected to intestinal IR (20 min ischemia, 60 min reperfusion), 24 h after either control or ethanol (0.63 ml/kg) gavage, assaying mucosal mitochondrial respiration (MR), enterocyte mitochondrial membrane potential (MMP), and levels of mitochondrial cytochrome c. Compared with sham‐treated rats, IR decreased enterocyte mitochondrial respiratory function, membrane potential and cytochrome c content by 77%, 67%, and 61%, respectively. These effects were completely reversed in EPC rats. The protective effects of ethanol on MR and MMP were prevented in rats administered DMPX (adenosine A2 receptor antagonist), 10 min prior to EPC treatment; ethanol's protective effect on MMP was reproduced by administration of CPCA, an adenosine A2 receptor agonist. These results support the hypothesis that EPC prevents intestinal mucosal mitochondrial dysfunction through an adenosine‐dependent mechanism. Supported by AA14945 and DK43785.

How irritant is alcohol?

Alcohol-based hand rubs are used worldwide to prevent transmission of nosocomial pathogens. To investigate skin irritation caused by alcohols alone and in combination with detergent washing. Single and repetitive patch testing with 60-100% alcohols [ethanol, 1-propanol, 2-propanol (synonyms: isopropyl alcohol, isopropanol)], a positive control [0.5% sodium lauryl sulphate (SLS)] and negative controls (empty chamber and water) were performed. Wash tests were performed with 80% ethanol and 0.5% SLS on the forearms with each agent alone and with both agents in a tandem design. Skin hydration, erythema and barrier disruption [measured as transepidermal water loss (TEWL)] were evaluated (always 15 volunteers). We found no significant change in skin barrier or erythema induced by the alcohols in the patch tests, whereas skin hydration decreased significantly. Application of alcohols to previously irritated skin did not show a stronger skin barrier disruption than application of SLS alone. Wash tests demonstrated that alcohol application caused significantly less skin irritation than washing with a detergent (TEWL, P < 0.001; skin hydration, P < 0.05; erythema, P < 0.05). Even on previously irritated skin, ethanol did not enhance irritation. By contrast, a protective effect of ethanol used after skin washing was observed (TEWL, P < 0.05; skin hydration, P < 0.05; erythema, P < 0.05). Alcohol-based hand rubs cause less skin irritation than hand washing and are therefore preferred for hand hygiene from the dermatological point of view. An alcohol-based hand rub may even decrease rather than increase skin irritation after a hand wash due to a mechanical partial elimination of the detergent.

Brewing controversies: Darwinian perspective on the adaptive and maladaptive effects of caffeine and ethanol as dietary autonomic modulators

Ethanol and caffeine are two of the oldest human drugs. Their pervasive integration into the modern human diet may reflect behavioral attempts to correct maladaptations induced by evolutionary displacement of the autonomic system. The dietary adoption of caffeine may parallel the emergence of cognition as an independent basis of competition. Enhancement of the cognitive ability to gather and process information likely evolved as a valuable adjunct to physical behavior in prehistoric fight-or-flight encounters. Caffeine effectively exploits this pre-existing association between adrenergic activity and cognitive readiness, leading to its use in the modern environment where success in competition increasingly depends on cognitive, rather than physical, prowess. Ethanol may have emerged as a dietary means to buffer the maladaptive chronic sympathetic activation and fear response associated with stressful lifestyles and the social phobias associated with the dissolution of kin networks. We explore the health implications of ethanol and caffeine use, with particular attention to their acute and chronic effects on the autonomic axis. The putative protective effects of ethanol in surviving major trauma or reducing inflammation and heart disease may relate to tempering the behavioral and cardiovascular consequences of catastrophic or chronic sympathetic activation. Acute or chronic abuse of ethanol manifests paradoxical pro-adrenergic effects such as tremors and insomnia that may partly represent compensatory responses. Compensatory remodeling may also explain why confirmation of detrimental effects related to caffeine-induced sympathetic activation has proven elusive; indeed, paradoxical pro-vagal benefits may eventually be recognized. Ethanol and caffeine are potential agents that may beneficially expand the dynamic range of the autonomic system. In an environment where the Darwinian value of knowledge has increasingly supplanted that of physical traits, the consumption of caffeine and alcohol may represent both a cause and an effect of modern human evolution.

Role of adenosine receptors in the protective effect of ethanol on gut ischemia / reperfusion induced hepatocellular injury in rats.

Role of adenosine receptors in the protective effect of ethanol on gut ischemia / reperfusion induced hepatocellular injury in rats.

Carbohydrate carbon sources induce loss of flocculation of an ale-brewing yeast strain.

To identify the nutrients that can trigger the loss of flocculation under growth conditions in an ale-brewing strain, Saccharomyces cerevisiae NCYC 1195. Flocculation was evaluated using the method of Soares, E.V. and Vroman, A. [Journal of Applied Microbiology (2003) 95, 325]. Yeast growth with metabolizable carbon sources (glucose, fructose, galactose, maltose or sucrose) at 2% (w/v), induced the loss of flocculation in yeast that had previously been allowed to flocculate. The yeast remained flocculent when transferred to a medium containing the required nutrients for yeast growth and a sole nonmetabolizable carbon source (lactose). Transfer of flocculent yeast into a growth medium with ethanol (4% v/v), as the sole carbon source did not induce the loss of flocculation. Even the addition of glucose (2% w/v) or glucose and antimycin A (0.1 mg l(-1)) to this culture did not bring about loss of flocculation. Cycloheximide addition (15 mg l(-1)) to glucose-growing cells stopped flocculation loss. Carbohydrates were the nutrients responsible for stimulating the loss of flocculation in flocculent yeast cells transferred to growing conditions. The glucose-induced loss of flocculation required de novo protein synthesis. Ethanol prevented glucose-induced loss of flocculation. This protective effect of ethanol was independent of the respiratory function of the yeast. This work contributes to the elucidation of the role of nutrients in the control of the flocculation cycle in NewFlo phenotype yeast strains.

921 Role of adenosine receptors in the protective effect of ethanol on gut ischemia/reperfusion induced hepatocellular injury in rats

921 Role of adenosine receptors in the protective effect of ethanol on gut ischemia/reperfusion induced hepatocellular injury in rats

Melatonin in concentrated ethanol and ethanol alone attenuate methamphetamine-induced dopamine depletions in C57BL/6J mice.

The present study aimed to investigate the protective effects of melatonin, ethanol and temperature changes on methamphetamine-induced neurotoxicity in both sexes of mice. Mice exhibited a similar degree of striatal dopamine depletion when methamphetamine was administered during the light and dark cycles. Moreover, 10 mg/kg, but not 5 mg/kg, of methamphetamine, significantly increased body temperature even though dopamine depletions were observed following both doses. Melatonin (80 mg/kg) dissolved in 30% (v/v) ethanol and 30% ethanol alone exerted a moderate to full protection against methamphetamine-induced dopamine depletions in both sexes of mice, whereas the same dose of melatonin in 3% ethanol exerted no protective effect. Furthermore, ethanol attenuated methamphetamine-induced dopamine depletions in a dose-dependent manner with the exception of high efficacy of ethanol at low doses. Finally, the protective effects of ethanol were not blocked by bicuculline. Together, we conclude that ethanol may protect mice against methamphetamine-induced dopamine depletion probably via non-GABAA receptor activation.

Ethanol exposure inhibits the cytotoxic effect induced by gp120 in CHP100 human neuroblastoma cells.

The aim of present study was to investigate the acute effects of ethanol on cytotoxicity induced by HIV-1 coat protein gp120 in CHP100 human neuroblastoma cell line. We demonstrate that ethanol, within a range of clinically relevant concentrations (15-90 mM) prevents cell death elicited by gp120 (10 pM) in a dose dependent manner. This protective action seems to be mediated by a reduction of free intracellular Ca(2+) levels because ethanol, at concentrations ranging from 0.1-0.5%, is able to decrease gp120-stimulated Ca(2+) uptake up to 24%. Furthermore, our data show an involvement of NO/cGMP messenger system pathway, because ethanol is also able to reduce gp120-stimulated NO release (up to 45%) and cyclic GMP accumulation (up to 73%). These findings suggest that the protective effect of ethanol against gp120-induced cytotoxicity in CHP100 cells underlies a Ca(2+)-activated, NO/cGMP-dependent mechanism.

Alcohol and Platelet Function

Epidemiological studies have shown that moderate consumption of alcoholic beverages is inversely related to the incidence of the complications of coronary artery disease. The protective effect of ethanol may be partially attributable to an inhibitory effect of ethanol on platelets. This article summarizes the experimental observations that ethanol inhibits platelet responses to specific physiological agonists. In alcoholics, various platelet defects have been observed, but these may be influenced by metabolic factors rather than the presence of ethanol alone. The acute effects of ethanol on platelet functions both in vivo and ex vivo will be reviewed. Evidence will be presented demonstrating that ethanol added acutely in vitro inhibits phospholipase A2 in stimulated platelets. The interaction of ethanol with other signal transduction pathways will also be discussed.

Protective effect of ethanol on X-ray-induced mitotic recombination in Drosophila melanogaster.

The effect of ethanol pretreatment on X-ray-induced mitotic recombination in D. melanogaster females was investigated by means of the white/white+ (w/w+) spot test. White females inseminated by yellow males were allowed to oviposit for 8 hr on medium containing 5%, 7.5% and 10% (v/v) ethanol and submitted to 10 Gy of X-rays 52 hr after the beginning of the egg laying period (chronic treatments). For acute treatments 56 +/- 4-hr-old larvae grown in regular medium were held in petri dishes containing filter paper soaked with 50% (v/v) ethanol for 30 min before being irradiated with 10 Gy. The emerging heterozygous w/w+ females were inspected for the presence of white spots (LS) in their eyes. Acute ethanol pretreatments lead to a significant reduction in the frequency of LS. This is suggested to be due to the scavenging by ethanol of free radicals originating during irradiation. If so, the contribution of the indirect action of radiation to mitotic recombination induced by X-rays must be significant. Chronic ethanol pretreatments also resulted in a decrease of LS, though impairment of larval development by ethanol may have partly contributed to the effect observed. At the concentrations tested, ethanol by itself did not modify the frequency of LS observed in the control.

Effect of dietary ethanol on gallbladder absorption and cholesterol gallstone formation in the prairie dog

Dietary ethanol has been reported to protect against cholesterol gallstone formation. Because enhanced gallbladder absorption of water is important in cholesterol cholelithiasis, we examined the hypothesis that ethanol acts by inhibiting the absorptive function of the gallbladder. Eighteen adult male prairie dogs were fed a lithogenic liquid diet containing 0.4% cholesterol. Half of the animals received 30% of total calories as ethanol, whereas their pair-fed controls received equicaloric amounts of maltosedextrin. After 3 months, the gallbladders were inspected for gallstones and crystals, and gallbladder and hepatic bile were analyzed. Cholesterol stones and crystals were present in all nine controls. None of the alcohol-fed animals had stones, but four had cholesterol crystals. Gallbladder cholesterol, phospholipids, and total calcium were significantly decreased in alcohol-fed animals. In both gallbladder and hepatic bile, the cholesterol saturation index was significantly lower in alcohol-fed animals, as was the ratio of trihydroxy to dihydroxy bile salts. The ethanol-supplemented diet produced a significant decrease in the absorption of water by the gallbladder as indicated by changes in the gallbladder bile to hepatic bile ratios of the total bile salt concentration (7.29 ± 1.25 versus 3.84 ± 0.56; p <0.05) and the total calcium (3.37 ± 0.24 versus 2.43 ± 0.29; p <0.05). These findings indicate that the protective effect of ethanol may be related to its ability both to inhibit gallbladder absorption of water and to alter the composition of biliary lipids.

Electron transport and protection of liver slices in the late stage of paracetamol injury

Cell injury by chemicals takes place in two stages, initial chemical interaction between the material and cell components, and subsequent stages of adaptation or failure of response to chemical modincation of some parts of the cell apparatus. Paracetamol toxicity was studied in an in vitro system using liver slices incubated in two stages. During the first 2 hr slices were exposed to 10 mM paracetamol and this was absent during the following 4 hr of incubation. Damage was quantified at the end by measuring leakage of lactate dehydrogenase (LDH), increase in water content and potassium loss. Treatment of slices with 10 μM DCPIP or 2 mM ethanol in the second period of incubation prevented paracetamol-induced damage. The protective effect was not dependent on the activity of P450 since the second stage of incubation was insensitive to SKF-525A. The protective effect of ethanol was blocked by the presence of 1 mM pyrazole suggesting that ethanol needs to be metabolized to exert its effect. The addition of 20 mM pyruvate reversed the protection provided by ethanol. Nicotinamide did not alter toxicity or protection by ethanol. These findings suggest an increase of NADH and NADH/NAD ratio as the most probable explanation for the protective effect observed. The role of reducing equivalents in detoxification of quinones such as NAPQI by formation of hydroquinones, is discussed in relation to the mechanism of cell injury by paracetamol.

Comparison of anticonvulsant effect of ethanol against NMDA-, kainic acid- and picrotoxin-induced convulsions in rats

The anticonvulsant effect of ethanol against N-methyl-D-aspartic acid-(NMDA), kainic acid-, and picrotoxin-induced convulsions was studied in rats. Ethanol (2 g/kg, ip) offered protection against these agents, and it was most effective against picrotoxin and least effective against kainic acid. MK801, NMDA receptor antagonist, also provided protection against these agents. However, it was most effective against NMDA and least effective against kainic acid. Ineffective doses of MK801 (0.1 mg/kg, ip) and ethanol (0.5 g/kg, ip), when administered concurrently, had a facilitatory anticonvulsant effect, thereby providing protection against mortality following severe convulsions induced by NMDA or picrotoxin, but not against kainic acid. The protective effect of ethanol against NMDA- and kainic acid-induced neurotoxicity, in contrast to picrotoxin-induced toxicity, was not reversed by imidazodiazepine, Ro 15-4513, an ethanol antagonist. Furthermore, Ro 15-4513 did not produce any proconvulsant effect with NMDA or kainic acid. These findings suggested that the anticonvulsant actions of ethanol may be attributed to its ability to antagonize NMDA-mediated excitatory responses and facilitate the GABAergic transmission.

RO15-4513 but not FG-7142 reverses anticonvulsant effects of ethanol against bicuculline- and picrotoxin-induced convulsions in rats.

The reversal of anticonvulsant effect of ethanol against chemoconvulsions by RO15-4513 was investigated in rats as this novel imidazobenzodiazepine (ethyl-8 azido-5, 6-dihydro-5-methyl-6-Oxo-4H-imidazo [1,5a] [1,4] benzodiazepine-3-carboxylate) is reported to antagonize the acute behavioral and biochemical effects of ethanol in animals. Reversal of ethanol effects on onset of myoclonic jerks, tonic extensor phase, mortality time and percent protection against mortality were compared with not only other anticonvulsant pentobarbital but also with another inverse agonist FG-7142. Pretreatment with RO15-4513 (4 mg/kg) reversed the protective effect of ethanol against bicuculline-induced tonic extensor phase and mortality (87%). This response was sensitive to reversal by RO15-1788 (10 mg/kg). However, onset of myoclonic jerks and duration of clonus were not significantly altered. It also reversed the effect against picrotoxin but the reversal against mortality was up to 50%. As compared to ethanol, RO15-4513 reversed partially the protective effect of pentobarbital against bicuculline- and picrotoxin-induced convulsions. FG-7142 failed to reverse the protective effect of ethanol and pentobarbital against bicuculline-induced tonic extensor phase although it reversed the effect against onset and mortality. It had no effect on the protective effect against picrotoxin-induced convulsions. Both RO15-4513 and FG-7142 possessed proconvulsant effects against bicuculline but not against picrotoxin. These observations suggest that RO15-4513 has a more preferential action against ethanol effects as compared to the other inverse agonist.