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)

The effects of PolyHb (intermolecularly crosslinked hemoglobin) and PolyHb-SOD-CAT (intermolecularly crosslinked hemoglobin, superoxide dismutase and catalase) on the production of hydroxyl radical was studied using a rat hindlimb model of ischemia-reperfusion. Hydroxyl radical generation was assessed by an indirect assay based on the hydroxylation of 4-hydroxybenzoate. The hydroxylation product, 3,4 dihydroxybenzoate (3,4 DHBA), was analyzed by high performance liquid chromatography and electrochemical detection. The identification of 3,4 DHBA was confirmed by analysis of authentic standard and an in vitro hydroxyl radical generation system. Ischemia was induced in both hindlimbs by ligation of the infrarenal aorta. After a 4hr ischemic period, hindlimbs were simultaneously perfused with PolyHb-SOD-CAT (5 g/dl) into one limb and PolyHb (5 g/dl) into the other limb via femoral arterial catheters. Each perfusate also contained the hydroxyl radical trap, 4-hydroxbenzoate (5 mM). Femoral venous effluents were analyzed for the presence of the 3,4 DHBA. Data indicates that greater 3,4 DHBA production occurs during PolyHb perfusion as compared to PolyHb-SOD-CAT. These preliminary results show that perfusion with PolyHb-SOD-CAT may alleviate oxidative stress in a model of ischemia-reperfusion.
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PMID:Reduction of hydroxyl radical generation in a rat hindlimb model of ischemia-reperfusion injury using crosslinked hemoglobin-superoxide dismutase-catalase. 908 37

Extensive evidence is available to show the importance of ischemia after severe human head injury. We have previously shown that pharmacologically increasing the release of oxygen in brain tissue where the local oxygen pressure is low reduces infarct size in animal models. To study the possible negative effects of this strategy, we tested the effect of an allosteric modifier of hemoglobin (RSR13) on free radical production in the rat acute subdural hematoma (ASDH) model, both under normoxic as well as under hyperoxic, normobaric conditions. When compared to baseline, induction of ASDH resulted in a significant increase (p < 0.05) in 2,3-DHBA (2,3 dihydroxybenzoic acid, produced from salicylate after attack by hydroxyl radicals) at 30 and 60 min postinduction, both for the control group (39% and 91%) as well as the RSR13-treated group (41% and 62%). The 2,5-DHBA also increased significantly (p < 0.05) in the drug-treated animals at the 30- and 60-min time points when compared to baseline (49% and 77%). At all time points, except the 30-min, the increase in 2,3-DHBA was less marked in the RSR13 animals than in the control group. Similarly, the 2,5-DHBA increase after ASDH was lower at all time points except for the 30-min time point in the RSR13-treated group. These results indicate that enhanced tissue oxygen release by the allosteric modifier of hemoglobin RSR13 does not increase hydroxyl radical production after ASDH. Clinical trials are needed to test this compound in humans after severe head injury.
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PMID:Reducing hemoglobin oxygen affinity does not increase hydroxyl radicals after acute subdural hematoma in the rat. 1009 57

This study sought to determine whether gallium-desferrioxamine (Ga/DFO) can curb free radical formation and mitigate biochemical and electrophysiological parameters of injury in the cat retina subjected to ischemia followed by reperfusion. For the biochemical studies, cat eyes were subjected to 90 min of retinal ischemia followed by 5 min of reperfusion, and enucleation of one eye of each cat was used to measure retinal reperfusion injury. Before enucleation of fellow eyes, 2.5 mg/kg Ga/DFO was injected intravenously 5 min before reperfusion. The flux of hydroxyl radicals, as measured directly by conversion of salicylate to 2,3- and 2,5-dihydroxybenzoic acid (2,3- and 2,5-DHBA), was significantly lower in Ga/DFO-treated eyes. The mean normalized level of 2,3-DHBA (considered a specific marker of hydroxyl radicals) was 3.5 times higher in untreated eyes. Ga/DFO caused a significant reduction, by 2.56-fold, in lipid peroxidation, as reflected by levels of malondialdehyde. Ascorbic acid, a natural antioxidant present in the retina, is severely depleted in untreated eyes. In contrast, in Ga/DFO-treated eyes, levels were 10 times higher than the control. Energy charge was 2.38 times higher in treated eyes. Levels of purine catabolites (hypoxanthine, xanthine, and uric acid) that reflect excessive metabolism of purine nucleotides were approximately twice higher in untreated retinas. Electroretionographic studies, performed on a different subset of animals, substantiated the biochemical results. In Ga/DFO-treated eyes the amplitude of the mixed cone-rod response b-wave (as compared with fellow nonischemic eyes) fully recovered within 24 h after ischemia (b-wave ratio 1.04 +/- 0.09, [mean +/- SEM]) whereas ischemic/reperfused and nontreated eyes recovered to only 0.33 +/- 0. 05. The results show that severe biochemical and functional retinal injury occurs in cat eyes subjected to ischemia and reperfusion. These severe changes were significantly reduced by a single administration of Ga/DFO just before reperfusion. We hypothesize that the protection afforded by Ga/DFO is due to a combined effect of "Push-Pull" mechanisms interfering with transition metal-dependent and free radical-mediated injurious processes.
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PMID:Gallium-desferrioxamine protects the cat retina against injury after ischemia and reperfusion. 1069 41

It has been suggested that stroke-prone spontaneously hypertensive rats (SHRSP) show vulnerability to neuronal damage following transient ischemia. To observe the effect of hydroxyl radicals on neuronal damage in the hippocampus of SHRSP during ischemia and recirculation, we measured the levels of 2,3-dihydroxybenzoic acid (2,3-DHBA), as a biological marker of hydroxyl radicals in the hippocampus of SHRSP, by high pressure liquid chromatography-electrochemical detection. The production of hydroxyl radicals in the hippocampus during the first 20 min of recirculation was a peak in all intervals. The changes in 2,3-DHBA levels during ischemia and recirculation in SHRSP were significantly higher than in Wistar-Kyoto rats. These results suggest that neuronal damage following ischemia and recirculation is, in part, caused by the increase in hydroxyl radicals during ischemia and recirculation.
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PMID:Increased hydroxyl radicals in the hippocampus of stroke-prone spontaneously hypertensive rats during transient ischemia and recirculation. 1140 31

The intensity of hydroxyl radical (OH*) formation in the myocardium during reperfusion after ischemia of different duration was evaluated using microdialysis with sodium salicylate. 2,3-Dihydroxybenzoic acid, a product of OH* trapping by salicylic acid, was used as a marker of OH* generation in the postischemic myocardium. Experiments were performed on open-chest anesthetized and jet-ventilated Wistar rats. The concentrations of 2,3-dihydroxybenzoic acid in the dialysate were measured by high performance liquid chromatography (HPLC) with electrochemical detection. Experiments showed that the intensity and duration of free oxygen radical generation during reperfusion after 30-min ischemia far surpassed those observed after 20-min ischemia.
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PMID:Formation of hydroxyl radicals during myocardial reperfusion after experimental ischemia of different duration. 1158 98

The present study used isolated rat hearts to investigate whether (1) Sheng-Mei-San (SMS), a traditional Chinese formulation comprising Radix Ginseng, Radix Ophiopogonis and Fructus Schisandrae, is protective against post-ischemic myocardial dysfunction, and (2) whether the cardioprotective effect of SMS is related to scavenging of hydroxyl radicals and opening the mitochondrial KATP channels. The excised hearts of male Sprague-Dawley rats were perfused on a Langendorff apparatus with Krebs-Henseleit solution with a gas mixture of 95% O2 and 5% CO2. Left ventricular end-diastolic pressure (LVEDP, mmHg), left ventricular developed pressure (LVDP, mmHg), +/-dP/dt (mmHg/s) and coronary flow (ml/min) were continuously monitored. All hearts were perfused for a total of 120 min consisting of a 30-min pre-ischemic period followed by a 30-min global ischemia and 60-min reperfusion. Lactate, lactate dehydrogenase (LDH) and 2,5-dihydroxybenzoic acid (2,5-DHBA) concentrations in the effluent were measured during reperfusion. Three days' treatment with SMS (1.67 ml/kg per day) inhibited the rise in LVEDP and improved the post-ischemic LVDP and +/-dP/dt significantly better than in the untreated control hearts during reperfusion. SMS increased the coronary flow at baseline, and during reperfusion. Pretreatment with 5-hydroxydecanoic acid (5-HD), a mitochondrial KATP channel blocker, abolished the inhibition of the rise in LVEDP, the increase in coronary flow and the improvement in LVDP and +/-dP/dt induced by SMS. SMS significantly attenuated the concentrations of lactate, LDH and 2,5-DHBA during reperfusion, but the pretreatment with 5-HD restored them; 5-HD alone did not affect the concentrations. SMS improved the post-ischemic myocardial dysfunction through opening the mitochondrial KATP channels.
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PMID:Sheng-Mai-San is protective against post-ischemic myocardial dysfunction in rats through its opening of the mitochondrial KATP channels. 1219 3

Although hydroxyl radical ((*)OH) formation has been implicated in the pathophysiological changes of ischemic stroke, (*)OH production in the core and penumbra regions is not clear. It is extremely important to distinguish penumbra from ischemic core in focal cerebral ischemia studies, because the penumbra contains viable tissue, which can be salvaged by appropriate treatment. This study evaluated (*)OH production in both core and penumbra regions of ischemic striatum during ischemia and reperfusion. Microdialysis probes were placed in striatal tissue of rats subjected to the middle cerebral artery occlusion model of ischemic stroke. The (*)OH-trapping agent 4-hydroxybenzoic acid (4-HBA) was administered by both i.v. and probe infusion. Dialysate levels of the 4-HBA oxidation products, 3,4-dihydroxybenzoic acid (3,4-DHBA), were determined by HPLC-ECD. After microdialysis probe delivery of 4-HBA, (*)OH production was significantly increased in the striatal core during both ischemia and reperfusion. Penumbra (*)OH production increased only during reperfusion. Alterations of 3,4-DHBA concentration in dialysate following i.v. 4-HBA administration were likely related to alterations in tissue blood flow. The findings were confirmed by a greater oxidation of dihydroethidium in the ischemic core than in the penumbra as determined by fluorescent microscopy. The findings of (*)OH production in ischemic striatum are the opposite of those reported for ischemic cortex and suggest critical regional variations in (*)OH production that may have significant clinical implications in the treatment of ischemic stroke.
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PMID:Hydroxyl radical formation is greater in striatal core than in penumbra in a rat model of ischemic stroke. 1260 15

Elevated generation of reactive oxygen species (ROS) has been demonstrated during ischemia and reperfusion. Dopamine (DA) autooxidation may contribute to increased ROS generation. The novel neuroprotective agent AM-36 has antioxidant and Na(+) channel blocking activity and reduces neuronal damage in both cortex and striatum after middle cerebral artery (MCA) occlusion. Here we sought in vivo evidence of the ability of AM-36 to inhibit intrastriatal ROS generation and DA release after ischemia. Salicylate hydroxylation coupled with in vivo microdialysis in the striatum of conscious Long Evans rats was performed during MCA occlusion by perivascular microinjection of endothelin-1 (ET-1). AM-36 (6 mg/kg) was administered intraperitoneally 30 min after MCA occlusion. Dialysates were analysed using high performance liquid chromatography with electrochemical detection for the salicylate hydroxylation product, 2,3-dihydroxybenzoic acid (2,3 DHBA) and for DA and metabolites. MCA occlusion resulted in a marked increase in 2,3 DHBA and a secondary increase in all analytes, 180-300 min later. Increased DA release coincided with 2,3 DHBA formation. AM-36 significantly reduced ischemia induced increases in 2,3 DHBA and DA, and infarct volume in the striatum. Significant improvements in a battery of behavioural tests was also found in AM-36 treated rats. This study has demonstrated profound inhibition of ROS generation by a novel compound with antioxidant activity, administered post-ischemia in conscious rats.
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PMID:AM-36, a novel neuroprotective agent, profoundly reduces reactive oxygen species formation and dopamine release in the striatum of conscious rats after endothelin-1-induced middle cerebral artery occlusion. 1268 77

This study examined whether quinaprilat, an angiotensin-converting enzyme inhibitor, reduces the infarct size, and investigated the mechanisms for its infarct size-reducing effect, in rabbits. Japanese white rabbits underwent 30 min of ischemia and 48 h of reperfusion. Quinaprilat (100 microg/kg/h or 300 microg/kg/h for 70 min, IV) was administered 20 min before ischemia with or without pretreatment with Nomega-nitro-l-arginine methyl ester (l-NAME) (10 mg/kg, IV, a nitric oxide synthase inhibitor), 5-hydroxydecanoic acid sodium salt (5-HD) or posttreatment with 5-HD (5 mg/kg, IV, a mitochondrial KATP channel blocker). The area at risk as a percentage of the left ventricle was determined by Evans blue dye and the infarct size was determined as a percent of the area at risk by triphenyl tetrazolium chloride staining. Using a microdialysis technique, myocardial interstitial levels of 2,5-dihydroxybenzoic acid (2,5-DHBA), an indicator of hydroxyl radicals, and NOx, an indicator of nitric oxide, were measured before, during, and after 30 min of ischemia. Quinaprilat significantly reduced the infarct size in a dose-dependent manner (30.1 +/- 3%, n = 10, and 27.6 +/- 2%, n = 7, respectively) compared with the control (46.5 +/- 4%, n = 10). The infarct size-reducing effect of quinaprilat was completely blocked by pretreatment with l-NAME (43.8 +/- 2%, n = 8) and 5-HD (50.1 +/- 3%, n = 8) and posttreatment with 5-HD (50.3 +/- 2%, n = 8), respectively. Quinaprilat did not affect the myocardial interstitial 2,5-DHBA level but significantly increased the NOx level during ischemia and reperfusion. Quinaprilat reduces myocardial infarct size involving NO production and mitochondrial KATP channels in rabbits without collateral circulation.
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PMID:Quinaprilat reduces myocardial infarct size involving nitric oxide production and mitochondrial KATP channel in rabbits. 1277 74

The relationship between hydroxyl radical (OH*) generation in the zone of ischemia/reperfusion and the size of infarction formed was investigated in 18-22-week-old anaesthetized male SHRSP and Wistar rats using a myocardial microdialysis technique. The marker of OH* generation, 2,3-dihydroxybenzoic acid (2,3-DHBA), was analyzed in dialyzates by high performance liquid chromatography with electrochemical detection. Myocardial ischemia was induced by ligation of the descending branch of the left main coronary artery for 30 min. The mean value of basal 2,3-DHBA level in the dialyzate samples from SHRSP (243 +/- 21 pg for 30 min) was significantly higher than that from Wistar rats (91 +/- 4 pg for 30 min, p < 0.0002); it positively correlated with left ventricular hypertrophy (r = 0.806; p < 0.05). During reperfusion total 2,3-DHBA output was 1.8-fold higher in SHRSP than in Wistar rats (659 +/- 60 pg versus 364 +/- 66 pg for 60 min, respectively, p < 0.0002). At the same time, 2,3-DHBA increase above the basal level was the same in Wistar and SHRSP rats (181 +/- 25 and 172 +/- 36 pg for 60 min, respectively). The infarct size in SHRSP (45.4 +/- 4.3%) was significantly higher (p < 0.05) than in Wistar rats (32.8 +/- 3.3%). There was a significant positive correlation between basal level of 2,3-DHBA and total reperfusion 2,3-DHBA content in SHRSP (r = 0.752; p < 0.05). Thus, data obtained clearly indicate that the hypertrophied myocardium of SHRSP was less tolerant to ischemia/reperfusion than that of Wistar rats due to chronically increased OH* production and enhanced total OH* output during reperfusion. Greater myocardial damage in SHRSP than in Wistar rats following the equal increase in OH* production above the basal level suggests the existence of deficit of the antioxidant defense in the hypertrophied myocardium.
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PMID:Role of reactive oxygen species in the sensitivity of rat hypertrophied myocardium to ischemia. 1506 99


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