Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ethanol is known to have a deleterious effect on liver ischemia-reperfusion injury, but recent reports suggest that light ethanol consumption may produce a protective effect in several organs. We aimed to investigate effects of different doses of ethanol on liver oxidative injury. Rats were fed with ethanol-containing diets (24, 30, 36, 40% for groups A, B, C, D, respectively). After four weeks, livers were exposed to ischemia-reperfusion. Chemiluminescence was recorded; total lipids, adenosine triphosphate, malondialdehyde, reduced glutathione and lactic dehydrogenase were assessed. In all groups, ischemia resulted in the disappearance of O2*-, a decrease in glutathione and adenosine triphosphate, and stable malondialdehyde values. During the reperfusion phase, O2*- production, malondialdehyde and lactic dehydrogenase increased, reaching significantly higher values in groups C and D and significantly lower values in group B. The effect of ethanol on ischemia-reperfusion injury seems to be a dose-related response, with an additional toxic effect only at high doses of ethanol.
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PMID:Oxygen free radical production in rat liver: dose-related effect of ethanol on reperfusion injury. 1134 49

Increased lysophosphatidylcholine (LPC) production by the ischemic heart is associated with tissue damage. In vitro, LPC produces an increase in cytosolic [Ca2+], usually followed by cell contracture and lysis. Since ethanol reportedly protect cells during ischemia-reperfusion, we wished to determine whether ethanol could protect heart cells against LPC-induced Ca2+ overload. Newborn rat heart cells in culture were loaded with Fura-2 and [Ca2+]i recorded in individual cells. The presence of 22 or 44 mM ethanol increased the time required for 10 microM x L-palmitoyl-LPC to produce maximal Ca2+ accumulation from 8.4+/-0.4 min (n=47) to 21.1+/-2.1 x min (n=32; P<0.01) and 23.8+/-1.8 min (n=10; P<0.01) respectively. The onset of the [Ca2+]i increase could be reversed partially by the addition of ethanol (44 or 88 mM). After the addition of 22 mM ethanol, the cells retained the Fura-2 three times longer than under control conditions. Ethanol (88 mM) decreased the critical micelle concentration of LPC, thus decreasing the LPC monomer concentration in this solution. La3+ also protected the cells against LPC but no further protection was afforded by the addition of ethanol. Our results suggest that ethanol concentrations commonly found in the blood of social drinkers protect heart cells against the deleterious effect of LPC.
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PMID:Ethanol delays and reverses lysophosphatidylcholine-induced calcium overload in neonatal rat heart cells. 1169 65

Although alcohol is well recognized as a systemic toxin, the enteric manifestations of alcohol abuse have only recently begun to be elucidated at the cellular and microvascular levels. Since the microvascular mechanism of the toxicity of alcohol has progressively been revealed, clinical applications of this research field should increase the availability of therapeutic options for alcohol-induced injuries of liver, pancreas and gastrointestinal (GI) tract. A high concentration of ethanol reduces GI and pancreas blood flow. Ethanol-induced GI hemorrhage, GI ulcer, and pancreatitis are initiated by the microcirculatory disturbance of GI mucosa and pancreas. Ethanol administration induces an increase in vasoactive agents such as endothelin and nitric oxide and oxidative stress. They appear to be involved in ethanol-induced GI and pancreatic injury. Regarding the effects of ethanol on the liver, small amount of ethanol increases hepatic blood flow, and prevents gut ischemia/reperfusion (I/R)-induced hepatic microvascular dysfunction and subsequent liver injury. While large amount of ethanol itself causes hepatic microvascular dysfunction, and aggravates the gut I/R-induced hepatic microvascular dysfunction and subsequent liver injury. Vasoactive agents and oxidative stress also appear to be involved in the liver injury. In endotoxemic animals, even small amount of ethanol causes hepatic microvascular dysfunction. Chronic ethanol consumption aggravates endotoxin-induced hepatic microvascular dysfunction. Chronic ethanol consumption aggravates gut I/R-induced leukostasis in the liver and hepatocellular injury associated with an enhanced expression of adhesion molecules, while it prevents the gut I/R-induced sinusoidal perfusion injury. Thus, effects of chronic ethanol consumption on the I/R injury are still controversial.
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PMID:[Effect of alcohol on organ microcirculation: its relation to hepatic, pancreatic and gastrointestinal diseases due to alcohol]. 1172 32

The cardioprotective effects of red wine have been attributed to several polyphenolic antioxidants including resveratrol and proanthocyanidins. The goal of the present study was to determine whether white wines could also provide cardioprotection. Three different white wines (white wine #1, #2 and #3) were chosen for this study. Ethanol-free extracts of the wines were prepared by vacuum evaporation. Rats weighing approximately 200 g were given either 50 mg/kg or 100 mg/kg of each wine extract for 3 weeks. The rats were anesthetized and sacrificed and their hearts were excised for the preparation of isolated working rat heart. All hearts were subjected to 30 min of global ischemia followed by 2 h of reperfusion. Cardiac function including heart rate, left ventricular developed pressure (LVDP), maximum first derivative of developed pressure (LVdp/dtmax), left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEP), aortic flow (AF) and coronary flow (CF) were continuously monitored and myocardial infarct size was measured at the end of the experiments. The results of our study demonstrated that among the three different white wines, only white wine #2 conferred cardioprotection as evidenced by improved postischemic ventricular recovery compared with controls. The same white wine at a dose of 50 mg/kg also showed improvement in postischemic contractile recovery but the differences compared with controls were not significant. The amount of malondialdehyde production from these hearts was lower than that found in control hearts, indicating reduced formation of reactive oxygen species in white wine #2-treated rats. In vitro studies using a chemiluminescence technique revealed that white wine #2 scavenged both superoxide anions and hydroxyl radicals. The results of our study demonstrate that white wine #2 provided cardioprotection and the cardioprotective effect of the wine can be attributed, at least in part, to its ability to function as an in vivo antioxidant.
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PMID:Cardioprotection with white wine. 1207 62

Recent data indicate that acute alcohol exposure can have a preconditioning-like protective effect on the heart. We investigated the effect of ethanol exposure shortly before regional ischemia in an infarct model. Both in the open-chest rabbit and in the isolated rabbit heart, exposure of the heart to ethanol significantly reduced infarct size, but only if the alcohol were washed out or sufficiently metabolized before the onset of ischemia. If ethanol were still present during ischemia, it could not only prevent its own protective effect, but also abolish protection induced by ischemic preconditioning or the mitochondrial K(ATP) channel activator diazoxide. In the in vitro model, we tested for possible mediators of ethanol-induced protection and made comparisons to the signaling cascade of ischemic preconditioning. Neither adenosine receptor blockade with 8-(p-sulfophenyl) theophylline, scavenging of free radicals with N-2-mercaptopropionyl glycine, nor closure of K(ATP) channels with glibenclamide affected ethanol's protective effect. However, either a PKC inhibitor or a protein tyrosine kinase inhibitor could completely block ethanol-induced infarct size reduction. Both the protective and anti-protective effects of ethanol had a threshold of about 5 mM. Thus, ethanol-induced protection is mediated by protein kinase C and at least one protein tyrosine kinase, but, in contrast to ischemic preconditioning, is not triggered by either adenosine receptors, free radicals, or K(ATP) channels. Ethanol can only exert its protective effect if it is removed before the onset of ischemia. If still present during ischemia, ethanol has the opposite effect, and inhibits preconditioning by an as yet unidentified mechanism.
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PMID:The protective and anti-protective effects of ethanol in a myocardial infarct model. 1207 65

Long-term ethanol consumption at low to moderate levels exerts cardioprotective effects in the setting of ischemia and reperfusion (I/R). The aims of this study were to determine whether 1) a single orally administered dose of ethanol [ethanol preconditioning (EtOH-PC)] would induce a biphasic temporal pattern of protection (early and late phases) against the inflammatory responses to I/R and 2) adenosine and nitric oxide (NO) act as initiators of the late phase of protection. Ethanol was administered as a bolus to C57BL/6 mice at a dose that achieved a peak plasma concentration of ~45 mg/dl 30 min after gavage and returned to control levels within 60 min of alcohol ingestion. The superior mesenteric artery was occluded for 45 min followed by 60 min of reperfusion beginning 10 min or 1, 2, 3, 4, or 24 h after ethanol ingestion, and the numbers of fluorescently labeled rolling and firmly adherent (stationary) leukocytes in single postcapillary venules of the small intestine were quantified using intravital microscopic approaches. I/R induced marked increases in leukocyte rolling and adhesion, effects that were attenuated by EtOH-PC 2-3 h before I/R (early phase), absent when assessed after 10 min, 1 h, and 4 h of ethanol ingestion, with an even more powerful late phase of protection reemerging when I/R was induced 24 h later. The anti-inflammatory effects of late EtOH-PC were abolished by treatment with adenosine deaminase, an adenosine A(2) (but not A(1)) receptor antagonist, or a NO synthase (NOS) inhibitor during the period of EtOH-PC. Preconditioning with an adenosine A(2) (but not an A(1)) receptor agonist in lieu of ethanol 24 h before I/R mimicked the protective actions of late phase EtOH-PC. Like EtOH-PC, the effect of preconditioning with an adenosine A(2) receptor agonist was abrogated by coincident NOS inhibition. These findings suggest that EtOH-PC induces a biphasic temporal pattern of protection against the proinflammatory effects of I/R. In addition, our observations are consistent with the hypothesis that the late phase of EtOH-PC is triggered by NO formed secondary to adenosine A(2) receptor-dependent activation of NOS during the period of ethanol exposure.
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PMID:Preconditioning with ethanol prevents postischemic leukocyte-endothelial cell adhesive interactions. 1218 Nov 32

Moderate alcohol consumption is related to a reduction in cardiovascular deaths. Lysophosphatidylcholine (LPC) produces arrhythmias similar to those induced by ischemia most likely due to its uncoupling properties. We assessed effects of LPC in the presence of ethanol in cardiac myocyte pairs using the double whole-cell voltage-clamp technique. Ethanol 11, 22 and 44 mmol.l(-1) did not change junctional conductance for up to 25 min but postponed the time for total uncoupling induced by 20 micromol.l(-1) LPC from 11.3+/-3.0 min ( n=4), respectively, to 16.0+/-0.5 ( n=3; P=0.05), 20.5+/-1.9 min ( n=4; P<0.05) and 27.0+/-3.5 min ( n=3; P=0.01; mean+/-SEM). LPC-induced uncoupling which might occur during ischemia may be counteracted by ethanol.
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PMID:Ethanol protects against lysophosphatidylcholine-induced uncoupling of cardiac cell pairs. 1239 87

Ingestion of alcoholic beverages at low to moderate levels 24 h prior to ischemia and reperfusion (I/R) prevents postischemic leukocyte/endothelial cell adhesive interactions, a phenomenon referred to as late ethanol preconditioning (EtOH-PC). The aim of this study was to determine whether oxidants act as initiators of late EtOH-PC. Ethanol was instilled into the stomachs of C57BL/6 mice as a bolus by gavage at a dose that produced a peak plasma concentration of 45 mg/dl 30 min after administration and returned to control levels 60 min after ingestion. Twenty four hours later, the superior mesenteric artery was occluded for 45 min followed by 70 min of reperfusion. The numbers of rolling and firmly adherent leukocytes were quantified in postcapillary venules of the small intestine in sham animals (no EtOH-PC, no I/R), in mice subjected to I/R alone or EtOH-PC + I/R, and in animals treated with Mn-TBAP (a cell-permeant superoxide dismutase mimetic), oxypurinol (a XO inhibitor), the NAD(P)H oxidase inhibitors PR-39 or apocynin, or oxypurinol plus PR39 during the period of EtOH-PC on Day 1 followed by I/R on Day 2. In separate groups of mice, oxypurinol or apocynin were also administered 1 h after ethanol ingestion on Day 1, with induction of I/R 24 h later. I/R induced marked increases in leukocyte rolling and adherence, effects that were completely prevented by EtOH-PC. Coincident treatment with Mn-TBAP, oxypurinol, PR-39, apocynin, or oxypurinol plus PR-39 with ethanol attenuated these anti-inflammatory actions of EtOH-PC. However, administration of oxypurinol or apocynin 1 h after ethanol ingestion failed to prevent these protective effects of EtOH-PC. Our results indicate that reactive oxygen species formed during the period of ethanol exposure on Day 1 trigger the development of an anti-inflammatory phenotype that renders the small bowel resistant to the proadhesive effects of I/R 24 h later.
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PMID:Late preconditioning by ethanol is initiated via an oxidant-dependent signaling pathway. 1254 52

This study has examined the hypotheses that, firstly, the ethanol induces delayed cellular protection in mouse cardiac myocytes against subsequent sustained simulated ischemia (SI). Secondly, the delayed cyto-protective effect induced by the ethanol depends more on time than the dose in mouse cardiac myocytes. Finally, ethanol-induced delayed cellular protection in mouse cardiac myocytes is mediated through inducible nitric oxide synthase (iNOS). Accordingly, we planned the following groups of BALB/c mouse cultured cardiac myocytes in our study: (a) SI, (b) 5 mM ethanol (ETOH)/15 min + SI, (c) 5 mM ETOH/30 min + SI, (d) 10 mM ETOH/15 min + SI, (e) 10 mM ETOH/30 min + SI, (f) 25 mM ETOH/15 min + SI, (g) 25 mM ETOH/30 min + SI, (h) 25 mM ETOH/60 min + SI, (i) 50 mM ETOH/15 min + SI, (j) 50 mM ETOH/30 min + SI, (k) 50 mM ETOH/60 min + SI, (l) 250 mM ETOH/15 min + SI and (m) 250 mM ETOH/30 min + SI. Another set of experiments we designed with iNOS-/- and its wild-type (iNOS+/+) mice cardiac myocytes as follows: SI, 5 mM ETOH/30 min + SI, 10 mM ETOH/30 min + SI, 25 mM ETOH/30 min + SI, 50 mM ETOH/30 min + SI and 250 mM ETOH/30 min + SI. Cellular injury was measured by the release of creatinine kinase (CK, U/l) into the medium. BALB/c mouse cardiac myocytes subjected to SI demonstrated significant increase in CK release as compared to the ethanol-treated cells. Ethanol-induced delayed cellular protection resulted in a significant (p < 0.001) attenuation in the cellular injury as indicated by reduction in the release of CK (U/l) from 9.25 +/- 0.52 to 5.16 +/- 0.44 (5 mM ETOH/30 min), from 7.50 +/- 0.43 (10 mM ETOH/15 min) to 4.16 +/- 0.64 (10 mM ETOH/30 min), from 5.91 +/- 0.41 (25 mM ETOH/15 min) to 2.50 +/- 0.58 (25 mM ETOH/30 min) and to 2.25 +/- 0.37 (25 mM ETOH/60 min), from 5.41 +/- 0.28 (50 mM ETOH/15 min) to 1.66 +/- 0.56(50 mM ETOH/30 min) and to 1.25 +/- 0.30 (50 mM ETOH/60 min), and from 5.25 +/- 0.21(250 mM ETOH/15 min) to 1.66 +/- 0.51(250 mM ETOH/30 min). Reduction in CK release from ethanol-treated iNOS-/-mouse cardiac myocytes was insignificant (p > 0.05) compared to non-treated wild-type (iNOS+/+) mouse cardiac myocytes subjected to SI alone. Our data suggest that ethanol induces delayed cellular protection in mouse cardiac myocytes against sustained simulated ischemia. Further, ethanol-induced delayed cellular protection depends more on time than the dose. Furthermore, ethanol-induced delayed cellular protection is dependent on iNOS.
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PMID:Ethanol induced delayed cellular protection in mouse cardiac myocytes: role of inducible nitric oxide synthase. 1458 18

Reactive oxygen species play a critical role in ischemic injury and oxidative stress induces apoptosis and triggers inflammation in neural cells. The effect of ethanol on ischemic brain injury was examined. Ethanol attenuated ischemia/reperfusion-induced brain infarction and elevation of inflammatory mediators, including tumor necrosis factor-alpha (TNF-alpha) expression, metalloproteinase-9, and neutrophil-associated myeloperoxidase activities. In cultured neurons, ethanol suppressed combined oxygen and glucose deprivation (COGD)/reoxygenation-induced oxidative stress and neuronal apoptosis. Furthermore, ethanol suppressed COGD/reoxygenation-induced activation of NF-kappaB, a free-radical-sensitive regulator, leading to the attenuation of TNF-alpha expression in glial cultures. We propose that scavenging of free radicals and attenuation of free-radical-induced alterations might account for ethanol's beneficial action against ischemic brain injury.
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PMID:Ethanol attenuates ischemic and hypoxic injury in rat brain and cultured neurons. 1460 May 3


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