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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Polyphenolic compounds present in red wines, such as the flavonol quercetin, are thought capable of cardioprotection through mechanisms not yet clearly defined. It has been established that mitochondria play a critical role in myocardial recovery from ischemia-reperfusion (I-R) damage, and in vitro experiments indicate that quercetin can exert a variety of direct effects on mitochondrial function. The effects of quercetin at concentrations typically found in 1-2 glasses of red wine on cardiac I-R and mitochondrial function in vivo are not known. Quercetin was administered to rats (0.033 mg/kg per day by gavage for 4 d). Isolated Langendorff perfused hearts were subjected to I-R, and cardiac functional parameters determined both before and after I-R. Mitochondria were isolated from post-I-R hearts and their function assessed. Compared to an untreated control group, quercetin treatment significantly decreased the impairment of cardiac function following I-R. This protective effect was associated with improved mitochondrial function after I-R. These results indicate that oral low dose quercetin is cardioprotective, possibly via a mechanism involving protection of mitochondrial function during I-R.
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PMID:Mitochondrial function in response to cardiac ischemia-reperfusion after oral treatment with quercetin. 1203 6

Rat H9c2 myoblasts were preconditioned by heat or metabolic stress followed by recovery under normal conditions. Cells were then subjected to severe ATP depletion, and stress-associated proteotoxicity was assessed on 1) the increase in a Triton X-100-insoluble component of total cellular protein and 2) the rate of inactivation and insolubilization of transfected luciferase with cytoplasmic or nuclear localization. Both heat and metabolic preconditioning elevated the intracellular heat shock protein 70 (HSP70) level and reduced cell death after sustained ATP depletion without affecting the rate and extent of ATP decrease. Each preconditioning attenuated the stress-induced insolubility among total cellular protein as well as the inactivation and insolubilization of cytoplasmic and nuclear luciferase. Transient overexpression of human HSP70 in cells also attenuated both the cytotoxic and proteotoxic effects of ATP depletion. Quercetin, a blocker of stress-responsive HSP expression, abolished the effects of stressful preconditioning but did not influence the effects of overexpressed HSP70. Analyses of the cellular fractions revealed that both the stress-preconditioned and HSP70-overexpressing cells retain the soluble pool of HSP70 longer during ATP depletion. Larger amounts of other proteins coimmunoprecipitated with excess HSP70 compared with control cells deprived of ATP. This is the first demonstration of positive correlation between chaperone activity within cells and their viability in the context of ischemia-like stress.
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PMID:Stressful preconditioning and HSP70 overexpression attenuate proteotoxicity of cellular ATP depletion. 1210 62

Reactive oxygen species may be actively involved in the genesis of various pathological states such as ischemia-reperfusion injury, cancer, and diabetes. Our objective was to determine if subacute treatment with combined antioxidants quercetin and coenzyme Q(10) (10 mg/kg/day ip for 14 days) affects the activities of antioxidant enzymes in normal and 30-day streptozotocin-induced diabetic Sprague-Dawley rats. Quercetin treatment raised blood glucose concentrations in normal and diabetic rats, whereas treatment with coenzyme Q(10) did not. Liver, kidney, heart, and brain tissues were excised and the activities of catalase, glutathione reductase, glutathione peroxidase, superoxide dismutase, and concentrations of oxidized and reduced glutathione were determined. In the liver of diabetic rats, superoxide dismutase, glutathione peroxidase, and levels of both oxidized and reduced glutathione were significantly decreased from the nondiabetic control, and these effects were not reversed when antioxidants were administered. In kidney, glutathione peroxidase activity was significantly elevated in the diabetic rats as compared to nondiabetic rats, and antioxidant treatment did not return the enzyme activity to nondiabetic levels. In heart, catalase activity was increased in diabetic animals and restored to normal levels after combined treatment with quercetin and coenzyme Q(10). Cardiac superoxide dismutase was lower than normal in quercetin- and quercetin + coenzyme Q(10)-treated diabetic rats. There were no adverse effects on oxidative stress markers after treatment with quercetin or coenzyme Q(10) singly or in combination. In spite of the elevation of glucose, quercetin may be effective in reversing some effects of diabetes, but the combination of quercetin + coenzyme Q(10) did not increase effectiveness in reversing effects of diabetes.
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PMID:Effects of combined quercetin and coenzyme Q(10) treatment on oxidative stress in normal and diabetic rats. 1224 89

Renal ischemia-reperfusion injury occurs in many clinical conditions such as hypovolemic shock, thromboembolism, injury and after renal transplantation. Under these conditions, ROS are considered to be the reason for cellular damage. Bioflavonoids have antioxidant and renoprotective properties. We studied the effect of quercetin, a bioflavonoid, on ischemia and reperfusion in rats. The rats (n = 28) were separated into three groups. Group I was the control group. Animals in groups II (IR) and III (IR + Q) underwent 30 min ischemia and 45 min reperfusion, respectively. Rats, in group III, also received 50 mg kg(-1) quercetin before 45 min of reperfusion. The activities of SOD, CAT, GPx, and concentrations of GSH and GSSGR were determined in renal cortex and erythrocytes. Also, the levels of MDA in renal cortex and plasma, and XO in renal cortex were measured in these groups. The renal cortex XO levels in the IR group were higher than that of the control and IR+Q groups (p<0.001). The renal cortex and plasma MDA levels in the IR group were also found to be higher than the control and IR+Q groups (p<0.01, and p<0.001, respectively). However, a decrease in MAD level of the IR+Q group was found in renal cortex and erythrocytes. In addition, SOD, CAT, and GPx activities in renal cortex and erythrocytes of quercetin-treated animals were enhanced compared to animals of the IR group. Furthermore, there were no significant differences in the SOD, CAT, and GPx activities of the control and IR+Q group. A reduction of GSH and GSSGR levels in IR and IR+Q groups was detected but no significant differences were found between these groups. This study stresses that high concentration of ROS leads to renal ischemia and reperfusion, and quercetin reduces the renal injury by preventing the oxidative stress dependent on ischemia and reperfusion. Quercetin may be used in renal transplantation as an antioxidant drug.
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PMID:The effect of quercetin on renal ischemia and reperfusion injury in the rat. 1241 62

The aim of this study was to determine whether the medicinal herbs growing in Okinawa and possessing a radical-scavenging activity would exert cardioprotective effects against ischemia-reperfusion injury using isolated perfused rat hearts. Effects of the aqueous extracts from Psidium guajava L. and Limonium wrightii at concentrations having an equipotent radical-scavenging activity on myocardial injury produced by global ischemia followed by reperfusion were tested and were further compared with those of quercetin and gallic acid, major antioxidative components of P. guajava L. and L. wrightii, respectively. Both extracts significantly attenuated ischemic contracture during ischemia and improved myocardial dysfunction after reperfusion. Decreases in high-energy phosphates and increases in malondialdehyde in the reperfused hearts were significantly lessened with both plant extracts. Quercetin and gallic acid also exerted similar beneficial effects. These results indicate that P. guajava L. and L. wrightii both have cardioprotective effects against myocardial ischemia-reperfusion injury in isolated rat hearts, primarily through their radical-scavenging actions.
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PMID:Cardioprotective effects of extracts from Psidium guajava L and Limonium wrightii, Okinawan medicinal plants, against ischemia-reperfusion injury in perfused rat hearts. 1257 8

Glutamate-induced excitotoxicity is associated with a selective loss of retinal neurons after retinal ischemia and possibly in glaucoma. Since heat shock protein (HSP) 70 is known to play a protective role against ischemic neuronal injury, which is also linked to excitotoxicity, we studied the expression of inducible (HSP72) and constitutive (HSC70) forms of HSP70 in apoptosis of retinal ganglion cells (RGCs) after intravitreal injection of 8 nmoles N-methyl-D-aspartate (NMDA), a glutamate receptor agonist. Approximately 18 h after NMDA injection, there were increased numbers of TUNEL-positive cells and cells with elevated HSP72 immunoreactivity in the retinal ganglion cell layer (RGCL), but there were no noticeable changes in HSC70 immunoreactivity. These HSPs positive cells were also Thy-1 positive, a marker for RGCs. Hyperthermic pre-conditioning, which is known to induce HSPs, given 6 or 12 h prior to NMDA injection ameliorated neuronal loss in the RGCL as counted 7 days after NMDA injection but pre-conditioning at 18 h prior to NMDA injection did not have any ameliorative effect. Quercetin, an inhibitor of HSP synthesis, abolished the ameliorative effect of hyperthermic pre-conditioning. Pre-conditioning elevated HSP72 but not HSC70 immunoreactivity and reduced the number of TUNEL-positive cells in the RGCL at 18 h. Our results suggest that intravitreal injection of NMDA induces an up-regulation of HSP72 in a time-dependent manner but not HSC70 in RGCs, indicating a stress response of HSP72 in RGCs and other inner retinal neurons after exposure to NMDA. Hyperthermic pre-conditioning given within a therapeutic window is neuroprotective to the retina against NMDA-induced excitotoxicity, likely by inhibiting apoptosis through the modulation of HSP72 expression.
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PMID:Hyperthermic pre-conditioning protects retinal neurons from N-methyl-D-aspartate (NMDA)-induced apoptosis in rat. 1270 53

The high morbidity, high socioeconomic costs and lack of specific treatments are key factors that define the relevance of brain pathology for human health and the importance of research on neuronal protective agents. Epidemiological studies have shown beneficial effects of flavonoids on arteriosclerosis-related pathology in general and neurodegeneration in particular. Flavonoids can protect the brain by their ability to modulate intracellular signals promoting cellular survival. Quercetin and structurally related flavonoids (myricetin, fisetin, luteolin) showed a marked cytoprotective capacity in in vitro experimental conditions in models of predominantly apoptotic death such as that induced by medium concentrations (200 M) of H2O2 added to PC12 cells in culture. Nevertheless, quercetin did not protect substantia nigra neurons in vivo from an oxidative insult (6-hydroxydopamine), probably due to difficulties in crossing the blood-brain barrier. On the other hand, treatment of permanent focal ischemia with a lecithin/quercetin preparation decreased lesion volume, showing that preparations that help to cross the blood-brain barrier may be critical for the expression of the effects of flavonoids on the brain. The hypothesis is advanced that a group of quercetin-related flavonoids could become lead molecules for the development of neuroprotective compounds with multitarget anti-ischemic effects.
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PMID:Neuroprotection by flavonoids. 1466 45

Flavonoids are an important group of recognized antioxidants ubiquitous in fruits, vegetables and herbs. There are epidemiological evidences for the stroke-protecting capacity of flavonoids and while the neuroprotective power of complex extracts rich in flavonoids like those of Ginkgo biloba, green tea or lyophilized red wine have been demonstrated in several studies, neuroprotection by individual flavonoids has been poorly studied in vivo. The neuroprotective capacity of individual flavonoids was studied in PC12 cells in culture and in a model of permanent focal ischemia (permanent Middle Cerebral Artery Occlusion - pMCAO). In the in vivo experiments, flavonoids were administered in lecithin preparations to facilitate the crossing of the blood brain barrier. The simultaneous incubation of PC12 cells with 200 micro M hydrogen peroxide (H2O2) and different flavonoids for 30 min resulted in a conspicuous profile: quercetin, fisetin, luteolin and myricetin significantly increased cell survival while catechin, kaempherol and taxifolin did not. Quercetin was detected in brain tissue 30 min and 1 h after intraperitoneal administration. When one of the protective flavonoids (quercetin) and one of those that failed to increase PC12 cell survival (catechin) were assessed for their protective capacity in the pMCAO model, administered i.p. 30 min after vessel occlusion, quercetin significantly decreased the brain ischemic lesion while catechin did not. It is concluded that when administered in liposomal preparations, flavonoids structurally related to quercetin could become leads for the development of a new generation of molecules to be clinically effective in human brain ischemia.
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PMID:Cell culture protection and in vivo neuroprotective capacity of flavonoids. 1471 46

There is increasing evidence to suggest that toxic oxygen radicals play a role in the pathogenesis of ischemia/reperfusion (I/R) injury in the kidney. This study was designed to investigate the effects of quercetin (Qr), a bioflavonoid in ischemia-reperfusion induced renal failure in rats. The effect of quercetin against the damage inflicted by reactive oxygen species (ROS) during renal I/R was investigated in Sprague-Dawley rats using histopathological and biochemical parameters. In one set of experiments, animals were unilaterally nephrectomized and subjected to 45 min of left renal pedicle occlusion, and in another set both renal pedicles were occluded for 45 min followed by 24 h of reperfusion. Quercetin (2 mg/kg, 30 mg/kg, i.p. and 100 mg/kg, p.o.) was administered 2 h prior to ischemia. At the end of the reperfusion period, rats were sacrificed. Thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) levels, glutathione reductase (GR), catalase (CAT), and superoxide dismutase (SOD) activities were determined in renal tissue. Serum creatinine and blood urea nitrogen (BUN) concentrations were measured for the evaluation of renal function. Ischemic control animals demonstrated severe deterioration of renal function, renal morphology and a significant renal oxidative stress. Pretreatment of animals with quercetin (2 mg/kg and 30 mg/kg, i.p.) markedly attenuated renal dysfunction, morphological alterations, reduced elevated TBARS levels and restored the depleted renal antioxidant enzymes, whereas the (100 mg/kg, p.o.) dose of quercetin failed to revert the renal I/R induced changes. The findings imply that ROS play a causal role in I/R induced renal injury and quercetin exerts protective and deleterious effects in the kidney, depending upon the dose.
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PMID:The effect of quercetin, a bioflavonoid on ischemia/reperfusion induced renal injury in rats. 1882 41

We previously reported that Choto-san acts as an antioxidant and cytoprotective agents against H2O2-induced oxidative damage in NG108-15 cells, and the effect is due at least partly to the phenolic compounds. To further investigate the detail mechanisms of this cytoprotection effects of Choto-san and related compounds on enzyme activities of antioxidant systems were examined. Choto-san (5-100 microg/ml) and Chotoko (5-100 mg/ml) stimulated the activity of superoxide dismutase (SOD), catalase and glutathione peroxidase (GPX). These also increased the level of glutathione. Although Choto-san without Chotoko (w/o CKO) did not show the effects on SOD and catalase, GPX activity and glutathion content also, but weakly, stimulated by w/o CKO. The effects of phenolic compounds, epicatechin, caffeic acid and quercetin were also investigated. Epicatechin stimulated catalase, GPX and glutathion content, but not SOD. On the other hand, caffeic acid stimulated SOD activity but had no effects on others. Quercetin stimulated all, although intensities were different among. These results suggest that simultaneous induction of cellular antioxidant defense systems by Choto-sam and its related constituents may be an important mechanisms underlying the protective effects of Choto-san on ischemia-induced neuronal cells injury, and the characteristics of the stimulative effects of phenolic compounds were depend on enzymes.
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PMID:Effects of Choto-san and its related constituents on endogenous antioxidant systems. 1563 63


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