Showing papers on "Oxidative stress published in 1986"

Biochemistry of Oxidative Stress

Abstract: As a normal attribute of aerobic life, structural damage to organic compounds of a wide variety (DNA, proteins, carbohydrates and lipids) may occur as a consequence of oxidative reactions. Oxidative damage inflicted by reactive oxygen species has been called “oxidative stress”. Biological systems contain powerful enzymatic and nonenzymatic antioxidant systems, and oxidative stress denotes a shift in the prooxidant/antioxidant balance in favor of the former. Diverse biological processes such as inflammation, carcinogenesis, ageing, radiation damage and photobiological effects appear to involve reactive oxygen species. This field of research provides new perspectives in biochemical pharmacology, toxicology, radiation biochemistry as well as pathophysiology.

Increased Cerebral Glucose‐6‐Phosphate Dehydrogenase Activity in Alzheimer's Disease May Reflect Oxidative Stress

Abstract: The activities of the hexose monophosphate pathway enzymes glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase were measured at autopsy in control and Alzheimer's disease brains. Enzyme activities did not vary between different areas of brain and were unaltered by age. In Alzheimer's disease, the activities of both enzymes were increased, the glucose-6-phosphate dehydrogenase activity being almost double the activity of normal controls. We propose that this increased enzyme activity is a response to elevated brain peroxide metabolism.

Sickle cell membranes and oxidative damage.

Abstract: Sickle erythrocytes and their membranes are susceptible to endogenous free-radical-mediated oxidative damage which correlates with the proportion of irreversibly sickled cells. The suppression of incubation-induced oxidative stress by antioxidants, free radical scavengers and an iron chelator suggest that oxidation products of membrane-bound haemoglobin contribute towards the pathology of the disease.

The effect of high glucose and oxidative stress on lens metabolism, aldose reductase, and senile cataractogenesis

Abstract: Diabetic cataractogenesis, a multifactorial process, was examined with nuclear magnetic resonance (NMR). P-31 NMR spectroscopic studies showed substantial alteration of both energy and membrane metabolism in the diabetic lens. Findings from a C-13 NMR spectroscopic determination of the sorbitol pathway flux in lenses incubated in 35.5 mmol/L glucose revealed that (1) one-third of total glucose consumed was channeled through this pathway, and (2) the turnover rate of NADPH to NADP was 3,000%/hr. Furthermore, a competition for NADPH between aldose reductase and glutathione reductase was demonstrated. It is important to note that all metabolic changes in hyperglycemic/diabetic lenses can be prevented by aldose reductase inhibitors, eg, sorbinil.

Neutrophil-endothelial cell interaction. Evidence for and mechanisms of the self-protection of bovine microvascular endothelial cells from hydrogen peroxide-induced oxidative stress.

Abstract: Bovine microvascular endothelial cells (MEC) were able to degrade the H2O2 generated by phorbol myristate acetate-activated bovine neutrophils or by glucose oxidase with a maximal capacity of 4.0 +/- 1.2 (SD) nmol/10(6) cells/min, corresponding to the H2O2 released by about 3 X 10(6) neutrophils. H2O2 degradation occurred via the glutathione redox cycle and catalase. Degradation via the glutathione redox cycle was coupled with a marked stimulation of the hexose monophosphate shunt activity. The effect of H2O2 on ethidium bromide exclusion and on succinate oxidation was studied. Neither parameter was altered when MEC were exposed to H2O2 produced at rates within their degradative capacity. As soon as this was exceeded, impairment of both functions occurred. It is concluded that endothelial cells can protect themselves from H2O2-induced injury in a well-defined range of environmental H2O2 concentrations by actively degrading the peroxide.

Effects of Oxidative Stress Caused by Hyperoxia and Diquat. A Study in Isolated Hepatocytes

Abstract: The effects of oxidative stress caused by hyperoxia or administration of the redox active compound diquat were studied in isolated hepatocytes, and the relative contribution of lipid peroxidation, glutathione (GSH) depletion, and NADPH oxidation to the cytotoxicity of active oxygen species was investigated. The redox cycling of diquat occurred primarily in the microsomal fraction since diquat was found not to penetrate into the mitochondria. Depletion of intracellular GSH by pretreatment of the animals with diethyl maleate promoted lipid peroxidation and sensitized the cells to oxidative stress. Diquat toxicity was also greatly enhanced when glutathione reductase was inhibited by pretreatment of the cells with 1,3-bis(2-chloroethyl)-1-nitrosourea. Despite extensive lipid peroxidation, loss of cell viability was not observed, with either hyperoxia or diquat, until the GSH level had fallen below approximately 6 nmol/10(6) cells. The iron chelator desferrioxamine provided complete protection against both diquat-induced lipid peroxidation and loss of cell viability. In contrast, the antioxidant alpha-tocopherol inhibited lipid peroxidation but provided only partial protection from toxicity. The hydroxyl radical scavenger alpha-keto-gamma-methiol butyric acid, finally, also provided partial protection against diquat toxicity but had no effect on lipid peroxidation. The results indicate that there is a critical GSH level above which cell death due to oxidative stress is not observed. As long as the glutathione peroxidase - glutathione reductase system is unaffected, even relatively low amounts of GSH can protect the cells by supporting glutathione peroxidase-mediated metabolism of H2O2 and lipid hydroperoxides.

Role of acetaldehyde and xanthine oxidase in ethanol-induced oxidative stress.

Abstract: Single doses of ethanol (5 g/kg, intragastric) produce oxidative stress in the liver as well as in the heart. The metabolism of acetaldehyde through xanthine oxidase appears to play an important role in the production of oxidative stress in the heart, but it has only a contributory role in the liver. It is suggested that, as oxidative stress through lipid peroxidation may produce organ pathology, the metabolic pathway of acetaldehyde through xanthine oxidase may be one of the mechanisms which mediate cardiac pathology in alcoholism.

Induction of Oxidative Stress by Silver Nanoparticles in Cultured Leydig Cells

Abstract: Nanomaterials have been used to create unique devices at the nanoscale level. However, the toxicities of nanomaterials have not been fully tested and the risk of nanomaterials has been raised as an emerging issue in these days. In this study, the cytotoxicity of silver nanoparticles was tested using cultured mouse leydig cells. As results, silver nanoparticles showed cytotoxicity with the generation of reactive oxygen species (ROS). With the increased level of ROS, intracellular glutathione level was decreased. DNA fragmentation and caspase -3 activation suggested the apoptotic mechanism of cell death in leydig cells treated with silver nanoparticles.

The protective effect of glucose on soluble rat lens hexokinase in the presence of oxidative stress.

Abstract: An in vitro animal model was used to characterize the protective effect of glucose on lenses subjected to oxidative stress. Paired rat lenses were incubated in TC-199 medium for six hours in the presence of an oxidant (0.06 mM H2O2, superoxide produced from 5 mM purine, or hydroxyl radical) and 2 mM glucose (control) or no glucose (experimental). Soluble hexokinase (HK) specific activity and lactate production were measured. 0.06 mM H2O2 inactivates 48% of the hexokinase in the absence of glucose; with glucose present hexokinase activity is reduced only 26%. Control experiments without oxidants show a statistically insignificant difference between hexokinase activities in the 0 and 2 mM groups, suggesting that the changes observed are not simply due to the presence or absence of glucose. Hexosemonophosphate shunt activity increases nearly 2.5-fold in the presence of 0.06 mM H2O2 and 2.0, 4.0 or 5.5 mM glucose. This suggests that the loss of hexokinase (a -SH enzyme) in the presence of H2O2 and 0 mM glucos...

Cadmium-induced COX-2 Expression in Cerebrovascular Endothelial Cells

Abstract: In order to get insight into the mechanism of cadmium (Cd) -induced brain injury, we investigated the effects of Cd on the induction of COX-2 in bEnd.3 mouse brain endothelial cells. Cd induced COX-2 expression and PGE2 release, which were attenuated by thiol-reducing antioxidant N-acetylcysteine (NAC) indicating oxidative components might contribute to these events. Indeed, Cd increased cellular reactive oxygen species (ROS) level and DNA binding activity of nuclear factor -kB (NF-κB), an oxidative stress sensitive transcription factor. Cd-induced PGE2 production and COX-2 expression were significantly attenuated by Bay 11 7082, a specific inhibitor of NF-κB and by SB203580, a specific inhibitor of p38 mitogen activated protein kinase (MAPK). These data suggest that Cd induces COX-2 expression through activation of NF-κB and p38 MAPK, the oxidative stress-sensitive signaling molecules, in brain endothelial cells.

Induction of unscheduled DNA synthesis in human mononuclear leukocytes by oxidative stress.

Abstract: The effect on unscheduled DNA synthesis (UDS) of different agents that induce oxidative stress was investigated using human mononuclear leukocytes (HML). It was found that Xanthine plus Xanthine oxidase increaseed UDS by 47%. Hydrogen peroxide had no significant effect. Cumene hydroperoxide increases UDS by 50% with a large interindividual variation (7–100%). Bleomycin and Mitomycin C increase UDS 189% and 295%, respectively. The validity of UDS induced by these agents for screening interindividual differences in susceptibility to oxidative stress is discussed.

Reactive oxygen species formed in vitro and in cells: role of thiols (GSH). Model studies with xanthine oxidase and horseradish peroxidase.

Abstract: Reactive oxygen species are being widely studied with respect to their biological significance. When a disturbance occurs in the delicate balance between prooxidants and antioxidants in favor of the former, there is a biological response thought to be the basis of a number of physiological and pathophysiological phenomena. This condition is being referred to as oxidative stress (see (1)).

Reactive oxygen species formed in vitro and in cells: role of thiols(gsh).

Abstract: Reactive oxygen species are being widely studied with respect to their biological significance. When a disturbance occurs in the delicate balance between prooxidants and antioxidants in favor of the former, there is a biological response thought to be the basis of a number of physiological and pathophysiological phenomena. This condition is being referred to as oxidative stress (see (1)). Among several biologically important types of reactive oxygen spe­ cies, we have been interested in recent years in those of photoemissive nature. The exposure of cells to oxidative conditions of diverse nature can be accompanied by an elevated production of free radicals which, in turn, is expressed as an enhanced generation of electronically excited states leading to the production of low-level chemiluminescence(see (2)). Studying the process of quinone redox cycling in intact cells and using low-level chemiluminescence as a parameter, we made the observation that, in contrast to our initial expectation, the level of photoemission elicited with a quinone, menadione, was decreased when cellular thiols were depleted rather than increased (3). This initial observation led to the study of the role of thiols and thiyl radicals in terms of metaboli­ cally generated reactive intermediates. This new area complements long­ standing interests in the field of radiation biochemistry, where thiols have been studied in a number of respects. The present work describes recent studies on thiol reactions in mo­ del reactions of enzymatic nature, xanthine oxidase and horseradish per­ oxidase.

Role of hexokinase in the regulation of glucose metabolism in human erythrocytes.

Abstract: Red blood cell glucose metabolism was studied in erythrocytes from a patient with trisomy 10 p which resulted in + 50% hexokinase specific activity, in normal controls and in cases of heterozygous hexokinase deficiency. The results obtained show that the hexokinase activity level is an important factor in the control of the erythrocyte's glycolytic rate while having no appreciable effect on the hexose monophosphate pathway under resting conditions. No clear conclusion could be drawn when an oxidative stress was present.