Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:1.15.1.1 (superoxide dismutase)
58,858 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Capillary occlusion is an early event in the development of diabetic retinopathy, and white blood cells have recently been shown to be involved. We have shown previously that pentoxifylline improves deformability and decreases F-actin content of unstimulated polymorphonuclear leukocytes from normal human subjects. The purpose of this study was to determine if pentoxifylline would improve three properties of unstimulated polymorphonuclear leukocytes from diabetic cats. The measured parameters were mechanical (whole cell deformability), structural (F-actin content) and biochemical (rate of superoxide anion production). Chronic hyperglycemia was induced in three cats by partial pancreatectomy, and they were kept in poor glycemic control for at least 6 months prior to the study. Polymorphonuclear leukocytes were isolated and the entry time of individual passive cells was measured during aspiration into a 4-micron micropipette under constant suction pressure (-15 cmH2O). Deformability was defined as the inverse of the entry time. F-actin content of passive cells was measured by NBD-phallacidin labeling followed by flow cytometry. The rate of superoxide anion production was measured spectrophotometrically by superoxide dismutase-inhibitable cytochrome c reduction. Following incubation for 15 min with 0.1, 1.0 and 10.0 mM pentoxifylline, the average entry time of passive polymorphonuclear leukocytes was reduced from control by 11 +/- 5% (P = 0.045), 17 +/- 6% (P = 0.007), and 36 +/- 5% (P < 0.001), respectively. The F-actin content decreased by 0%, 4 +/- 0.6% (P < 0.001), and 10 +/- 3% (P < 0.001), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Pentoxifylline modulates deformability, F-actin content, and superoxide anion production of polymorphonuclear leukocytes from diabetic cats. 133 31

Exposure to hyperglycemia slows the rate of proliferation of cultured human endothelial cells. Recently, it has been reported that glucose may autoxidize generating free radicals which have been hypothesized to delay cell replication time. To test whether oxidative stress has an effect on delaying cell replication time in hyperglycemic conditions, human endothelial cells cultured from umbilical veins were incubated in 5 or 20 mM glucose, either alone or in the presence of one of three different antioxidants: superoxide dismutase (SOD), catalase and glutathione (GSH). Cells grown in medium with 5 mM glucose, with or without antioxidants, yielded similar population doubling times and cell cycle phase distributions. Significantly lower growth parameters were observed in cells grown in medium with 20 mM glucose, without antioxidants. The presence of the antioxidant reverted them to almost normal growth. These data show that high glucose levels may delay endothelial cells replication time through the generation of free radicals, suggesting a possible pathophysiological linkage between the high levels of glucose and the development of microvascular complications of diabetes, possibly suggesting a new therapeutic approach to prevent such complications.
...
PMID:Decreased cultured endothelial cell proliferation in high glucose medium is reversed by antioxidants: new insights on the pathophysiological mechanisms of diabetic vascular complications. 148 70

Impaired endothelium-dependent relaxation occurs in diabetic rabbit aorta and normal aorta exposed to elevated concentrations of glucose and is prevented by cyclooxygenase inhibitors. The role of free radicals in the endothelial cell impairment was examined with free radical scavengers and in aortas from rabbits fed with probucol (1% wt/wt, a lipid-soluble antioxidant). Rings of aorta suspended for measurement of isometric tension were incubated for 6 h in control (5.5 mM) or elevated (44 mM) glucose. Impairment of endothelium-dependent relaxation to acetylcholine caused by exposure to elevated glucose was prevented by superoxide dismutase, catalase, deferoxamine, or allopurinol and did not occur in aortas from probucol-fed rabbits. Similarly, impairment of acetylcholine relaxations in aortas from alloxan-induced diabetic rabbits was restored to normal by superoxide dismutase. Oxygen-derived free radicals generated by xanthine oxidase also caused impaired acetylcholine relaxations. Exposure of aortic segments to elevated glucose or to xanthine oxidase caused a significant increase in release of immunoreactive prostanoids. These data indicate that the endothelial cell dysfunction caused by elevated glucose is mediated by free radicals that are likely generated through the increased cyclooxygenase catalysis occurring in the endothelium. Treatment with antioxidants protects against impaired endothelium-dependent relaxations caused by elevated glucose.
...
PMID:Free radicals mediate endothelial cell dysfunction caused by elevated glucose. 151 Jan 28

The ability of NiCl2 to prevent alloxan- and streptozotocin-induced hyperglycemia was tested in rats. NiCl2 injected before alloxan and streptozotocin prevented the hyperglycemic response to the drugs. The protective effect of NiCl2 was linked to an increase in the specific activity of Cu-Zn superoxide dismutase (SOD). The effect of NiCl2 on SOD activity might be related to the effect of nickel on calcium, copper and zinc concentrations.
...
PMID:Nickel chloride protection against alloxan- and streptozotocin-induced diabetes. 297 32

The potential of nickel chloride to prevent streptozotocin-induced hyperglycemia was tested in rats in vivo. To induce diabetes, streptozotocin (100 mg/kg body weight) was injected as a single dose. Streptozotocin treatment resulted in a significant decrease in plasma insulin and ceruloplasmin, and pancreatic Cu, protein, and Cu-Zn superoxide dismutase activity. In rats treated with nickel chloride (10 mg/kg body weight) and streptozotocin, these values were comparable with those observed in control rats. The results indicate that nickel chloride injected before streptozotocin prevented streptozotocin-induced hyperglycemia, and suggest that the protective effect was related to Cu-Zn superoxide dismutase activity, mediated by copper.
...
PMID:Effect of nickel chloride on streptozotocin-induced diabetes in rats. 304 20

Since oxygen free radicals may have a role in the pathophysiology of endotoxin shock, we have studied the effects of a wide range of compounds (alpha-tocopherol, reduced glutathione, allopurinol, superoxide dismutase (alone or in combination with catalase) and phenyl butylnitrone) that can act either to remove free radicals as they are generated or to prevent their generation. The effects of these substances on the metabolic and cardiovascular responses to endotoxin were examined in conscious rats. The intravenous infusion of endotoxin (10 mg/kg i.v. given over 4 h) resulted in systemic hypotension, transient tachycardia, an increase in plasma lactate, and an initial hyperglycemia followed, in those rats that died before 24 h, by hypoglycemia. The hypotension and tachycardia produced by endotoxin were not significantly modified by alpha-tocopherol, allopurinol, or superoxide dismutase, alone or in combination with catalase. The tachycardia was attenuated by reduced glutathione and phenyl butylnitrone. alpha-Tocopherol attenuated the initial hyperglycemia produced by endotoxin whilst alpha-tocopherol, allopurinol, and phenyl butylnitrone all significantly attenuated the endotoxin-induced increase in plasma lactate. Among the free radical scavenging systems studied, only alpha-tocopherol and phenyl butylnitrone improved survival. These results suggest a contribution from oxygen-free radicals to the pathophysiology of endotoxemia.
...
PMID:Modification by oxygen free radical scavengers of the metabolic and cardiovascular effects of endotoxin infusion in conscious rats. 374 40

Insulinopenic diabetes is known to produce endothelial dysfunction. This dysfunction could arise from either hyperglycemia or inadequate insulin. It is not known whether endothelial dysfunction occurs when hyperglycemia is present with elevated insulin levels. In this study, we utilized an experimental model of hyperglycemia with hyperinsulinemia to investigate latent endothelial dysfunction. Rats were continuously infused with glucose or saline for 72 h to achieve peak plasma glucose concentrations of approximately 25 mM. Plasma insulin rose by 12-fold in glucose-infused rats. No significant differences in serum electrolyte concentration were noted between control and glucose-infused rats after 72 h. Blood pressure was not altered by this intervention. Aortic rings taken from control rats relaxed to the endothelium-dependent vasodilators, acetylcholine and A-23187, and to the endothelium-independent vasodilator, nitroglycerin. Relaxation to acetylcholine but not to A-23187 or nitroglycerin was impaired in glucose-infused rat aortic rings. Incubation in vitro with either indomethacin or superoxide dismutase did not restore the impaired relaxation to acetylcholine in rings taken from glucose-infused rats. Thus hyperglycemia with hyperinsulinemia selectively impairs receptor-dependent, endothelium-dependent relaxation. These studies suggest that elevated glucose may be a common pathway leading to endothelial dysfunction in insulin-dependent diabetes mellitus and hyperglycemia-induced insulin resistance.
...
PMID:Endothelial dysfunction in a model of hyperglycemia and hyperinsulinemia. 757 26

Diabetic complications are believed to arise, in part, through an increase in oxidative stress. We characterized antioxidant status in vascular tissue in untreated diabetic rats and in diabetic rats rendered euglycemic by pancreatic islet transplantation. Three key endogenous antioxidant enzymes (e.g., superoxide dismutase, catalase, and glutathione peroxidase) were measured. Sprague-Dawley rats with streptozotocin-induced diabetes were killed after 8 weeks of untreated hyperglycemia and compared with age-matched controls. Eight weeks of untreated diabetes resulted in a significant increase of tissue catalase in aorta, iliac artery, and femoral artery as compared with controls. No significant changes in either superoxide dismutase or glutathione peroxidase were observed in aorta, iliac artery, or femoral artery of diabetic animals. This increase in catalase in diabetic vascular tissue suggests increased oxidative stress due to chronic exposure to H2O2 in vivo. To assess the impact of islet transplantation on oxidative stress in vascular tissue, inbred Lewis strain rats were rendered diabetic with streptozotocin. After 8 weeks of untreated diabetes, rats received an intraportal islet isograft and were monitored for 4 subsequent weeks of euglycemia. Islet transplantation improved weight gain and normalized blood glucose and total glycosylated hemoglobin. While catalase was significantly increased in aorta and iliac artery at 8 and 12 weeks of diabetes, vascular catalase was restored to normal by islet transplantation. These data suggest that islet transplantation is an effective treatment strategy to minimize increased oxidative stress in diabetic vasculature.
...
PMID:Peroxidative stress in diabetic blood vessels. Reversal by pancreatic islet transplantation. 762 92

Recent studies have demonstrated the protective effects of supplementing free oxygen radical scavenging enzymes against hyperglycemia-induced embryonic malformations. In this study, the glutathione (GSH)-dependent protection system in hyperglycemia-induced embryopathy was investigated. Rat embryos at the early head-fold stage (day 9.5) cultured in 66.7 mmol/l glucose for 48 h showed significant growth retardation and an increase in the frequency of malformations. The concentration of GSH and activity of the rate-limiting GSH-synthesizing enzyme, gamma-glutamylcysteine synthetase (gamma-GCS), significantly decreased in embryos exposed to hyperglycemia compared with controls (7.9 +/- 0.6 vs. 12.5 +/- 0.9 nmol/mg protein, P < 0.01 and 13.3 +/- 1.9 vs. 22.6 +/- 1.1 microU/mg protein, P < 0.01, respectively). Decreased activity of gamma-GCS in embryos exposed to hyperglycemia was associated with decreased expression of gamma-GCS mRNA levels. However, the activities of superoxide dismutase and glutathione peroxidase did not significantly change in these embryos. Extracellular and intracellular free oxygen radical formations estimated by Lucigenin-dependent chemoluminescence and flow cytometric analysis using 2',7'-dichlorofluorescein diacetate increased in isolated embryonic cells taken from embryos cultured under hyperglycemia. Supplementation of 2 mmol/l GSH ester into the hyperglycemic culture nearly restored GSH concentration in these embryos (11.9 +/- 0.5 vs. 12.5 +/- 0.9 nmol/mg protein) and reduced the formation of free oxygen radical species leading to almost complete normalization of growth retardation and embryonic dysmorphogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Significance of glutathione depletion and oxidative stress in early embryogenesis in glucose-induced rat embryo culture. 762 6

The effect of swimming-training upon the activities of the enzymes involved in the generation of reducing-equivalents (citrate synthase-mitochondria and glucose-6-phosphate dehydrogenase-cytosol) and of antioxidant enzymes (CuZn- and Mn-SOD, catalase and glutathione peroxidase) in the lymphoid organs (thymus, mesenteric lymph nodes and spleen) was examined. The skeletal muscles (soleus-red and gastrocnemius-white) were also studied. Although our data suggest an apparently random, organ-specific change in enzymatic activity, some interesting trends can be observed. Firstly, the increased citrate synthase and Mn-SOD activities observed in red, but not in white muscle, corroborate the well-known effect of endurance exercise-training on mitochondrial oxidative metabolism. Secondly, there was an inverse relationship between TBARs-monitored lipoperoxidation and glutathione peroxidase activity in all tissues studied, what is in accordance with the previous findings showing that such enzyme exerts the fine control of intracellular lipoperoxide concentration. Except in the case of the spleen, there was a trend for elevated glucose-6-phosphate dehydrogenase activity, coadjuvant of glutathione peroxidase in the antioxidant response to physical exercise in all tissues. Thirdly, Mn-SOD and catalase were conspicuously associated to oxidative stress in the thymus, while glutathione and catalase could be linked to this parameter in the spleen. Fourthly, the lymph nodes seem to be more dependent on the glucose-6-phosphate dehydrogenase/glutathione peroxidase pair for protection against damage promoted by physical exercise. Mn-SOD and catalase activities were lower in the lymph nodes after swimming training.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Superoxide dismutase, catalase, and glutathione peroxidase activities in muscle and lymphoid organs of sedentary and exercise-trained rats. 782 77


1 2 3 4 5 6 7 8 9 10 Next >>

---