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

Reactive oxygen species (ROS) have been implicated in a growing number of neurological disease states, from acute traumatic injury to neurodegenerative conditions such as Alzheimer's disease. Considerable evidence suggests that ROS also mediate ototoxicant- and noise-induced cochlear injury, although most of this evidence is indirect. To obtain real-time assessment of noise-induced cochlear ROS production in vivo, we adapted a technique which uses the oxidation of salicylate to 2,3-dihydroxybenzoic acid as a probe for the generation of hydroxyl radical. In a companion paper we described the development and characterization of this method in cochlear ischemia-reperfusion. In the present paper we use this method to demonstrate early elevations in ROS production following acute noise exposure. C57BL/6J mice were exposed for 1 h to intense broad-band noise sufficient to cause permanent threshold shift (PTS), as verified by auditory brainstem responses. Comparison of noise-exposed animals with unexposed controls indicated that ROS levels increase nearly 4-fold in the period 1-2 h following exposure and do not decline over that time. Our ROS measures extend previous results indicating that noise-induced PTS is associated with elevated cochlear ROS production and ROS-mediated injury. Persistent cochlear ROS elevation following noise exposure suggests a sustained process of oxidative stress which might be amenable to intervention with chronic antioxidant therapy.
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PMID:Early elevation of cochlear reactive oxygen species following noise exposure. 1043 15

We investigated the efficacy of histidine on potassium-depolarization induced hydroxyl radical (*OH) generation in the extracellular fluid of rat myocardium by a flexibly mounted microdialysis technique (O system). After the rat was anesthetized, a microdialysis probe was implanted in the left ventricular myocardium, and then sodium salicylate in Ringer's solution (0.5 nmol/microl per minute) was infused to detect the generation of *OH as reflected by the nonenzymatic formation of 2,3-dihydroxybenzoic acid (DHBA). Infusion of KCl (70 mM) clearly produced an increase in *OH formation. However, when KCl in the presence of a high concentration of histidine (25 mM) was infused through the microdialysis probe, KCl failed to increase the 2,3-DHBA formation. To examine the effect of histidine on ischemia-reperfusion of the myocardium, the heart was subjected to myocardial ischemia for 15 min by occlusion of the left anterior descending coronary artery (LAD). When the heart was reperfused, a marked elevation of the levels of 2,3-DHBA was observed in the heart dialysate. However, when corresponding experiments were performed with histidine (25 mM)-pretreated animals, histidine prevented the ischemia-reperfusion induced *OH formation trapped as 2,3-DHBA. These results indicate that histidine may protect against K+-depolarization-evoked *OH generation in rat myocardium.
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PMID:Protective effect of histidine on hydroxyl radical generation induced by potassium-depolarization in rat myocardium. 1046 66

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

During postischemic reperfusion, free radicals are produced and have deleterious effects in isolated rat hearts. We investigated whether melatonin (MEL) reduces the production of hydroxyl radical (*OH) in the effluent and aids in recovery of left ventricular (LV) function. Hearts were subjected to 30 min of ischemia followed by 30 min of reperfusion. Salicylic acid (SAL) was used as the probe for *OH, and its derivatives 2,5- and 2,3-dihydroxybenzoic acid (DHBA) were quantified using HPLC. In addition, thiobarbituric acid reactive substances (TBARS) in the myocardium was measured. Plateaus in the measurement of 2,5- and 2,3-DHBA were seen from 3 to 8 min after reperfusion in each group. The group that received 100 microM MEL+ SAL had significantly reduced amounts of 2,5- and 2,3-DHBA by multiple folds, compared to the SAL group. TBARS was significantly decreased in the 100 microM MEL group (1.20+/-0.36 vs 1.85+/-0.10 micromol/g of drug-free group, p<0.001). More importantly, the 100 microM MEL group significantly recovered in LV function (LV developed pressure, +dp/dt, and -dp/dt; 63.0%, 60.3%, and 59.4% in the 100 microM MEL group; 30.2%, 29.7%, and 31.5% in the drug-free group, respectively; p<0.05). Duration of ventricular tachycardia or ventricular fibrillation significantly decreased in the 100 microM MEL group (100 microM MEL, 159+/-67 sec; drug-free, 1244+/-233 sec; p<0.05). As a result of scavenging *OH and reducing the extent of lipid peroxidation, MEL is an effective agent for protection against postischemic reperfusion injury.
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PMID:Melatonin scavenges hydroxyl radical and protects isolated rat hearts from ischemic reperfusion injury. 1090 Dec 78

We examined the effect of fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, on the production of hydroxyl radical (*OH) generation via nitric oxide synthase (NOS) activation by an in vivo microdialysis technique. The microdialysis probe was implanted in the left ventricular myocardium of anesthetized rats and tissue was perfused with Ringer's solution through the microdialysis probe at a rate of 1 microl/min. Sodium salicylate in Ringer's solution (0.5 nmol/microl/min) was infused directly through a microdialysis probe to detect the generation of *OH. Induction of [K(+)](o) (70 mM) or tyramine (1 mM), significantly increased the formation of *OH trapped as 2,3-dihydroxybenzoic acid (DHBA). The application of N(G)-nitro-L-arginine methyl ester (L-NAME), a NOS inhibitor, significantly decreased the K(+) depolarization-induced *OH formation, but the effect of tyramine significantly increased the level of 2,3-DHBA. When fluvastatin (100 microM), an inhibitor of low-density lipoprotein (LDL) oxidation, was administered to L-NAME-pretreated animals, both KCl and tyramine failed to increase the level of 2,3-DHBA formation. The effect of fluvastatin may be unrelated to K(+) depolarization-induced *OH generation. To examine the effect of fluvastatin on ischemic/reperfused rat myocardium, the heart was subjected to myocardial ischemia for 15 min by occlusion of the left anterior descending coronary artery (LAD). When the heart was reperfused, a marked elevation of the level of 2,3-DHBA was observed. However, in the presence of fluvastatin (100 microM), the elevation of 2,3-DHBA was not observed in ischemia/reperfused rat heart. Fluvastatin, orally at a dose of 3 mg/kg/day for 4 weeks, significantly blunted the rise of serum creatine phosphokinase and improved the electrocardiogram 2 h after coronary occlusion. These results suggest that fluvastatin is associated with a cardioprotective effect due to the suppression of noradrenaline-induced *OH generation by inhibiting LDL oxidation in the heart.
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PMID:Effect of fluvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on nitric oxide-induced hydroxyl radical generation in the rat heart. 1133 4

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


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