Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30044 (antioxidant enzyme)
 8,037 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The study was undertaken to evaluate the cardioprotective potential of the flavonoids osajin and pomiferin against ischemia-reperfusion induced injury in rat hearts as a model of antioxidant-based composite therapy. Studies were performed with isolated, modified Langendorff-perfused rat hearts and ischemia of the heart was initiated by stopping the coronary flow for 30 min followed by 60 min of reperfusion (14 ml x min(-1)). Wistar rats were divided into four groups. The treated groups received osajin or pomiferin (5 mg/kg/day in 0.5% Avicel), the placebo group received only 0.5 Avicel; the intact group was left without any applications. Biochemical indicators of oxidative damage--malondialdehyde, superoxide dismutase, glutathione peroxidase, total antioxidant activity in serum and the myocardium have been evaluated. We also examined the effect of osajin and pomiferin on cardiac function: left ventricular end-diastolic pressure, left ventricular pressure, and peak positive dP/dt. Our results demonstrate that the flavonoids osajin and pomiferin attenuate the myocardial dysfunction provoked by ischemia-reperfusion. This was confirmed by an increase in both the antioxidant enzyme values and the total antioxidant activity. The cardioprotection provided by osajin and pomiferin treatment results from the suppression of oxidative stress and correlates with the improved ventricular function.
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PMID:[Protective effects of the flavonoids osajin and pomiferin on heart ischemia-reperfusion]. 1692 35

The present 15 days study was undertaken to evaluate the cardioprotective potential of the prenylated isoflavones osajin and pomiferin isolated from the infructences of Maclura pomifera, Moraceae, against ischemia-reperfusion induced injury in rat hearts as a model of antioxidant-based composite therapy. The study was performed on isolated, modified Langendorff-perfused rat hearts and the ischemia of heart was induced by stopping coronary flow for 30 min followed by 60 min of reperfusion (14 ml min(-1)). The Wistar rats were divided into four groups. The first treatment group received osajin (5 mg/kg/day in 0.5% Avicel); the second treatment group received pomiferin (5 mg/kg/day in 0.5% Avicel); the placebo group received only 0.5 Avicel; the last was an untreated control group. Biochemical indicator of oxidative damage-lipid peroxidation product malondialdehyde, antioxidant enzymes - superoxide dismutase, glutathione peroxidase, total antioxidant activity in serum and myocardium were evaluated. The effect of osajin and pomiferin on cardiac function, left ventricular end-diastolic pressure, left ventricular pressure and peak positive +dP/dt ischemia and reperfusion, also was examined. The results demonstrate that osajin and pomiferin attenuates the myocardial dysfunction provoked by ischemiareperfusion. This was confirmed by an increase in both antioxidant enzyme values and total antioxidant activity. The cardioprotection provided by osajin and pomiferin treatment results from the suppression of oxidative stress and this correlates with improved ventricular function.
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PMID:Effects of prenylated isoflavones osajin and pomiferin in premedication on heart ischemia-reperfusion. 1693 9

The mediators of acute exercise-induced preconditioning against ischemia-reperfusion injury are not understood. This study assesses the role of nitric oxide synthase (NOS), a reported mediator of other forms of preconditioning. Male Fischer 344 rats were divided into five groups (n = 6-7): sedentary (Sed); exercised 2 days on a treadmill at 20 m/min, 6 degrees grade, for 60 min (Run); sedentary, perfused with 100 microM N(omega)-nitro-l-arginine methyl ester hydrochloride (l-NAME) to inhibit NOS (Sed/L-N); exercised, perfused with l-NAME (Run/L-N); and exercised in a 4 degrees C environment, perfused with l-NAME (CRun/L-N). Twenty-four hours following exercise, isolated, perfused working hearts were subjected to 22.5 min of global ischemia plus 30 min of normoxic reperfusion. Left ventricle contents of several putative preconditioning mediators were determined. Postischemic recovery of cardiac output times systolic pressure was better in Run than Sed (78.4 vs. 50.2% of preischemia, P < 0.05). Inhibition of NOS did not abrogate the improved recovery in the exercise groups or alter recovery in Sed. All exercise groups also displayed improved myocardial efficiency (cardiac output times systolic pressure/oxygen consumption) postischemia and less lactate dehydrogenase release (P < 0.05). l-NAME appeared to lower lactate dehydrogenase release independent of exercise. The only change in antioxidant enzyme activity was a decrease in manganese superoxide dismutase in CRun/L-N (P < 0.05). Heat shock protein 72 expression increased only in Run and Run/L-N and endothelial NOS only in CRun/L-N (P < 0.05). Acute exercise-induced preconditioning of the Fischer 344 rat heart is not mediated by NOS and does not require increases in heat shock protein 72 or antioxidant enzymes.
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PMID:Improved postischemic function following acute exercise is not mediated by nitric oxide synthase in the rat heart. 1695 Oct 51

A transition zone between well-perfused proximal tissue and inadequately perfused distal tissue was evaluated histologically and biochemically in skin flaps. Cranially based pedicle flaps, 3 x 7.5 cm, were made on the backs of female Sprague-Dawley rats. Flap survival was 22% of the original flap area at 7 days and 40% at 14 days after flap elevation (p < 0.001). The transition zone consisted of full-thickness skin survival proximally and partial-thickness wound distally. It is evident that skin wounds induced by ischemia or reperfusion repair continuously between 7 and 14 days after flap elevation. Tissue glucose, lactate, and hypoxanthine levels were measured to assess capillary perfusion in the transition zone on postoperative day 3. The proximal full-thickness skin 5 mm from the wound margin demonstrated no significant changes in glucose and lactate levels compared with normal skin. The partial-thickness wounds exhibited no change in glucose (a 33% decrease was not statistically significant) but a significant increase (319% of normal) in lactate level (p < 0.05). Hypoxanthine levels increased to 453% of normal in full-thickness skin (p < 0.01) and to 787% in partial-thickness wounds (p < 0.001). Metabolic response was evaluated by enzyme assays in the transition zone. Hexokinase activity increased by 251% of normal (p < 0.05), glucose 6-phosphate dehydrogenase by 245% (p < 0.01), and glutathione reductase by 184% (p < 0.05) in the proximal full-thickness skin. Hexokinase activity further increased by 482% of normal (p < 0.01), glucose 6-phosphate dehydrogenase by 379% (p < 0.05), and glutathione reductase by 346% (p < 0.01) in partial-thickness wounds. The results suggest that partial-thickness wounds have less capillary circulation but greater antioxidant enzyme activities than does the survival area with full-thickness skin.
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PMID:Microanalyses of enzymes and metabolites in ischemia/reperfusion-induced partial-thickness skin wounds. 1716 2

Oxidative stress is central to ischemia-reperfusion injury. The role of the endoplasmic reticulum (ER) in this process is uncertain. In ER signaling, PERK-Nrf2 and Ire-CHOP are two pathways that determine cell fate under stress. PERK-Nrf2 up-regulates antioxidant enzyme expression whereas Ire-CHOP promotes apoptosis. We have identified a novel pathway in ER stress-induced apoptosis after ischemia-reperfusion in vitro involving translational suppression of the survival kinase PKB/Akt (Akt), and elucidated an alternative protective role of antioxidants in the regulation of Akt activity. Using human choriocarcinoma JEG-3 cells, we found that sustained activation of ER stress by tunicamycin or thapsigargin exacerbated apoptosis in oxygen-glucose-deprived cells during reoxygenation. This was mediated via a reduction in phosphorylated Akt secondary to down-regulation of protein translation rather than suppression of phosphorylation. Transient overexpression of wild-type Akt, but not kinase-dead Akt, in JEG-3 cells diminished tunicamycin-OGD reoxygenation-induced apoptosis. The antioxidants Trolox and Edaravone reduced apoptosis, but the protective effect of Trolox was abrogated by the PI3K inhibitor, LY294002. We speculate that sustained ER stress may contribute to the placental dysfunction seen in human pregnancy complications.
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PMID:Endoplasmic reticulum stress exacerbates ischemia-reperfusion-induced apoptosis through attenuation of Akt protein synthesis in human choriocarcinoma cells. 1716 73

Ischemic preconditioning (IPC) not only reduces local tissue injury caused by subsequent ischemia-reperfusion (IR) but may also have a beneficial effect on IR injury of tissues remote from those undergoing preconditioning. In this study, we investigated the effect of small intestinal IPC on renal IR injury in rats. Renal IR injury was induced by a 45-min renal artery occlusion and reperfusion for 2 or 24 h in rats with a previous contralateral nephrectomy, and ischemic preconditioning was induced by 3 cycles of 8-min ischemia and 5-min reperfusion of the small intestine. We then measured the concentrations of plasma creatinine (Cr) and blood urine nitrogen (BUN) and the level of malondialdehyde (MDA) and activities of superoxide dismutase (SOD) and catalase (CAT) in the renal cortex. Renal histopathology also was evaluated. Pretreatment with intestinal ischemic preconditioning significantly alleviated renal IR injury, as shown by decreases in the levels of Cr, BUN, and MDA, decreased renal morphologic change, and improved preservation of SOD and CAT activities. These results suggest that remote ischemic preconditioning of the small intestine protects against renal IR injury by inhibition of lipid peroxidation and preservation of antioxidant enzyme activities.
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PMID:Brief small intestinal ischemia lessens renal ischemia-reperfusion injury in rats. 1753 21

Oxidative stress underlies postoperative atrial fibrillation and electrophysiological remodelling associated with rapid atrial pacing. An increasing body of evidence indicates that the formation of reactive oxygen species (ROS) released following extracorporeal circulation are involved in the structural and functional myocardial impairment derived from the ischemia-reperfusion cycle. ROS behave as intracellular messengers mediating pathological processes, such as inflammation, apoptosis and necrosis, thereby participating in the pathophysiology of atrial fibrillation. Thus, increased superoxide (O(2)(.-)) production has been found in isolated atrial cardiomyocytes from patients with atrial fibrillation. Therefore, it seems reasonable to assume that the reinforcement of the antioxidant defense system should protect the heart against functional alterations in the cardiac rhythm. On this line, antioxidant enzyme induction through in vivo exposure to moderate concentration of ROS is associated with a reduction in the susceptibility of myocytes to ROS-induced injury. This response could be due to a prevailing effect of survival over apoptotic pathway. Previously, tissue preconditioning caused by prior exposure to an ischemia/reperfusion cycle has been successfully applied in experimental models and clinical settings associated with oxidative damage by ROS. However, such hypoxic preconditioning method is harmful to be applied to many clinical conditions associated with oxidative stress. In turn, experimental studies have revealed that non-enzymatic antioxidants produce a significant functional amelioration in cardiomyocytes subjected to an oxidative challenge. Moreover, clinical studies with patients scheduled for primary coronary artery bypass graft surgery had a reduced incidence of postoperative atrial fibrillation. We present the hypothesis of non-hypoxic preconditioning based on the association of pretreatment with n-3 polyunsaturated fatty acids followed by ascorbate plus alpha-tocoferol supplementation diminishes the incidence of postoperative atrial fibrillation in patients subjected to cardiac surgery with extracorporeal circulation.
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PMID:Non-hypoxic preconditioning of myocardium against postoperative atrial fibrillation: mechanism based on enhancement of the antioxidant defense system. 1754 71

The present study examines whether a subchronic probucol treatment of rats offers protection against ischemia-reperfusion (IR) injury in isolated perfused hearts. Sprague-Dawley rats were treated every second day per week with probucol (cumulative dose 120 mg/kg body mass, i.p.) for 4 weeks. In the probucol group, baseline myocardial antioxidant enzyme, glutathione peroxidase (GSHPx), activity was increased (p<0.05), whereas superoxide dismutase (SOD) and catalase (CAT) activities were not changed. Baseline oxidative stress, as indicated by the myocardial lipid peroxidation, was less (p<0.05) in the probucol group. Isolated hearts were subjected to 60 min global I and 20 min R. Recovery of the contractile function in globally ischemic hearts upon reperfusion was 36% in untreated group and 74% in the probucol group. After IR, GSHPx and CAT activities were significantly (p<0.05) higher in the probucol group compared with the control group, whereas SOD did not change. Lipid peroxidation owing to IR was significantly less in the probocol group. These data suggest that probucol treatment improves endogenous antioxidant reserve and protects against increased oxidative stress following IR injury.
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PMID:Probucol promotes endogenous antioxidant reserve and confers protection against reperfusion injury. 1761 53

Targeting of the antioxidant enzyme catalase to endothelial cells protects against vascular oxidative stress induced by hydrogen peroxide (H(2)O(2))(Am J Physiol 285:L283-L292, 2003; Nat Biotechnol 21:392-398, 2003; Am J Physiol 293:L162-L169, 2007). However, another reactive oxygen species, superoxide anion, is also involved in many forms of vascular oxidative stress, including ischemia/reperfusion, hypertension, and inflammation. To protect endothelium against superoxide attack, we designed and tested antibody-directed targeting of superoxide dismutase (SOD) to the endothelial surface determinant, platelet-endothelial cell adhesion molecule (PECAM)-1. We synthesized anti-PECAM/SOD conjugates that retained 70% of enzymatic activity (superoxide anion dismutation) and specifically bound to endothelial cells, but not PECAM-negative cells. The effect of anti-PECAM/SOD delivery to cells was tested in two distinct models of oxidative stress induced by either extracellular or intracellular generation of superoxide anion. In the first model, anti-PECAM/SOD, but not unconjugated SOD, protected endothelial cells against injury caused by superoxide produced in the medium by hypoxanthine-xanthine oxidase. At the optimal dose, anti-PECAM/SOD provided up to 40 to 50% protection against cell death in this model. In the second model, anti-PECAM/SOD at the optimal dose provided complete protection against necrosis caused by paraquat-induced intracellular superoxide generation. Endothelial targeting of SOD represents a new molecular antioxidant approach that could be used for the management of vascular oxidative stress.
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PMID:Platelet-endothelial cell adhesion molecule-1-directed endothelial targeting of superoxide dismutase alleviates oxidative stress caused by either extracellular or intracellular superoxide. 1771 41

Cerebral white matter injury, characterised by loss of premyelinating oligodendrocytes (pre-OLs), is the most common form of injury to the preterm brain and is associated with a high risk of neurodevelopmental impairment. The unique cerebrovascular anatomy and physiology of the premature baby underlies the exquisite sensitivity of white matter to the abnormal milieu of preterm extrauterine life, in particular ischaemia and inflammation. These two upstream mechanisms can coexist and amplify their effects, leading to activation of two principal downstream mechanisms: excitotoxicity and free radical attack. Upstream mechanisms trigger generation of reactive oxygen and nitrogen species. The pre-OL is intrinsically vulnerable to free radical attack due to immaturity of antioxidant enzyme systems and iron accumulation. Ischaemia and inflammation trigger glutamate receptor-mediated injury leading to maturation-dependent cell death and loss of cellular processes. This review looks at recent evidence for pathogenetic mechanisms in white matter injury with emphasis on targets for prevention and treatment of injury.
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PMID:Pathogenesis of cerebral white matter injury of prematurity. 1829 74


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