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1.
Central nervous system trauma and stroke. I. Biochemical considerations for oxygen radical formation and lipid peroxidation 总被引:23,自引:0,他引:23
The generation of oxygen radicals and the process of lipid peroxidation have become a focus of attention for investigators in the fields of central nervous system (CNS) trauma and stroke (e.g., ischemia). Considering our level of understanding of free radical and lipid peroxidation chemistry, absolute proof for their involvement in the pathophysiology of traumatic and ischemic damage to the CNS has been meager. While direct, unequivocal evidence for the participation of free radicals and lipid peroxidation as primary contributors to the death of neuronal tissue waits to be established, numerous recent studies have provided considerable support for the occurrence of free radical and lipid peroxidation reactions in the injured or ischemic CNS. In addition, the pharmacological use of antioxidants and free radical scavengers in the treatment of experimental CNS trauma and ischemia has provided convincing, although indirect evidence, for the involvement of oxygen radicals and lipid peroxidation in these conditions. The intent of this and its companion paper is to review: 1) the biochemical processes which may give rise to free radical reactions in the CNS, 2) the environment of the ischemic cell as it may affect the generation of oxygen radicals and the catalysis of lipid peroxidation reactions, 3) the evidence for the involvement of free radical mechanisms in CNS trauma and ischemia, and 4) the pathophysiological consequences of these phenomena. 相似文献
2.
D Becker S Swarts M Champagne M D Sevilla 《International journal of radiation biology and related studies in physics, chemistry, and medicine》1988,53(5):767-786
The reactions of the cysteine, glutathione and penicillamine thiyl radicals with oxygen and their parent thiols in frozen aqueous solutions have been elucidated through electron spin resonance spectroscopy. The major sulfur radicals observed are: (1) thiyl radicals, RS.; (2) disulfide radical anions. RSSR-.; (3) perthiyl radicals, RSS. and upon introduction of oxygen; (4) sulfinyl radicals, RSO., where R represents the remainder of the cysteine, glutathione or penicillamine moiety. The radical product observed depends on the pH, concentration of thiol, and presence or absence of molecular oxygen. We find that the sulfinyl radical is a ubiquitous intermediate in the free radical chemistry of these important biological compounds, and also show that peroxyl radical attack on thiols may lead to sulfinyl radicals. We elaborate the observed reaction sequences that lead to sulfinyl radicals, and, using 17O isotopic substitution studies, demonstrate that the oxygen atom in sulfinyl radicals originates from dissolved molecular oxygen. In addition, the glutathione thiyl radical is found to abstract hydrogen from the alpha-carbon position on the cysteine residue of glutathione to form a carbon-centered radical. 相似文献
3.
《Free radical research》2013,47(9):1103-1110
AbstractLipid-derived radicals and peroxides are involved in the pathogenesis of oxidative stress diseases and, although lipid peroxide production is a required reaction between a lipid radical and molecular oxygen, a useful lipid radical detection method has remained tentative. Also, the effect of oxygen concentration on lipid peroxide production must be considered because of the hypoxic conditions in cancer and ischemic regions. In this study, the focus was on nitroxide reactivity, which allows spin trapping with carbon-centred radicals via radical–radical reactions and fluorophore quenching through interactions with nitroxide's unpaired electron. Thus, the aim here was to demonstrate a useful detection method for lipid-derived radicals as well as to clarify the effects of oxygen concentration on lipid peroxide production using profluorescent nitroxide. This latter compound reacted with lipid-derived radicals in a manner inversely dependent on oxygen concentration, resulting in fluorescence due to alkoxyamine formation and, conversely, lipid peroxide concentrations decreased with lower oxygen in the reaction system. Furthermore, nitroxide inhibited lipid peroxide production and stopped oxygen consumption in the same solution. These results suggested that the novel application of profluorescent nitroxide could directly and sensitively detect lipid-derived radicals and that radical and peroxide production were dependent on oxygen concentration. 相似文献
4.
Free radicals have been associated with loss of viability of lyophilized bacteria exposed to oxygen. Free radical concentration was proportional to the log of the oxygen pressure in the sample. Sugars, such as lactose or sucrose, preserved viability and inhibited free radical production. Lyophilized tissue, particularly liver and spleen, also reacted with oxygen to produce free radicals, which appear to be associated with ascorbic acid in the tissues. Pure ascorbic acid in air does not produce free radicals, but when mixed with protein before lyophilization it reacts with oxygen in air. When a mixture of sodium ascorbate and phenylalanine or tryptophan is lyophilized, free radicals identical to those observed in tissue are obtained. Propyl gallate and di- or trihydroxybenzoates also react with oxygen when lyophilized with phenylalanine, but the g value of the free radical is significantly less than that obtained with ascorbate. A number of amino acids and similar nitrogenous compounds act as catalysts to form propyl gallate free radicals. As with the bacterial or tissue preparations, various sugars or similar carbohydrates inhibited free radical production by either ascorbate or gallate. In the absence of water the free radicals produced by the action of oxygen on lyophilized samples are stable for years. The rate of free radical production is increased by small amounts of moisture (exposure to moist air), but at humidities over 30% rh the radicals are unstable. 相似文献
5.
Mito F Kitagawa K Yamasaki T Shirahama C Oishi T Ito Y Yamato M Yamada K 《Free radical research》2011,45(9):1103-1110
Lipid-derived radicals and peroxides are involved in the pathogenesis of oxidative stress diseases and, although lipid peroxide production is a required reaction between a lipid radical and molecular oxygen, a useful lipid radical detection method has remained tentative. Also, the effect of oxygen concentration on lipid peroxide production must be considered because of the hypoxic conditions in cancer and ischemic regions. In this study, the focus was on nitroxide reactivity, which allows spin trapping with carbon-centred radicals via radical-radical reactions and fluorophore quenching through interactions with nitroxide's unpaired electron. Thus, the aim here was to demonstrate a useful detection method for lipid-derived radicals as well as to clarify the effects of oxygen concentration on lipid peroxide production using profluorescent nitroxide. This latter compound reacted with lipid-derived radicals in a manner inversely dependent on oxygen concentration, resulting in fluorescence due to alkoxyamine formation and, conversely, lipid peroxide concentrations decreased with lower oxygen in the reaction system. Furthermore, nitroxide inhibited lipid peroxide production and stopped oxygen consumption in the same solution. These results suggested that the novel application of profluorescent nitroxide could directly and sensitively detect lipid-derived radicals and that radical and peroxide production were dependent on oxygen concentration. 相似文献
6.
D D Pietronigro J E McGinness M J Koren R Crippa M L Seligman H B Demopoulos 《Physiological chemistry and physics》1979,11(5):405-414
Adriamycin semiquinone radicals are spontaneously generated by adriamycin solutions at physiologic pH. Rate of radical formation and equilibrium-state radical yield increase with increasing pH from 7.4 to 8.85. The radicals are oxygen sensitive, but the mechanism of radical formation is oxygen independent and associated with proton removal from the dihydroquinone of adriamycin. The less cardiotoxic and non-mutagenic (Ames test) anthracycline 5-iminodaunorubicin does not form semiquinone radicals spontaneously at physiologic pH. 相似文献
7.
K. T. Yamaguchi R. J. Stewart H. M. Wang S. E. Hudson M. Vierra A. Akhtar C. Hoffman D. George 《Free radical research》1992,16(3):167-174
Research in smoke inhalation has established that free radicals are produced from gases released during combustion and these species impair lung function. Using spin traps and their adducts in an animal model free radicals were measured. Various hyperbaric oxygen regimens were tested in an attempt to attenuate pulmonary damage caused by free radical reactions. Our data demonstrated that persistent oxygen- and carbon-centered free radicals are detectable in intravascular fluids after smoke inhalation. The smoke inhalation model showed however, clearing of spin trap adducts one hour after smoke exposure. Other researchers have found that when 100% oxygen is given at 1 atmosphere absolute (ATA) for 1 h, free radicals were not detectable. However, oxygen given at 2.5 ATA does produce detectable free radicals. With continued exposure at this pressure, the levels of free radicals increase for up to 60min. This study suggests that the level of free radical induced oxygen toxicity may be a function of oxygen pressure and duration of oxygen exposure. 相似文献
8.
M D Sevilla D Becker S Swarts J Herrington 《Biochemical and biophysical research communications》1987,144(2):1037-1042
Using Electron Spin Resonance spectroscopy at low temperatures, we find that thiyl radicals resulting from irradiation of frozen aqueous solutions of a variety of thiols, including cysteine, glutathione, and penicillamine react with oxygen to form sulfinyl (RSO.) radicals. The identity of the cysteine sulfinyl radical has been confirmed by the use of molecular oxygen isotopically labeled with 17O. Previous workers have suggested the reaction of thiyl radicals and molecular oxygen resulted in the formation of the potentially damaging thiol peroxyl radical, RSOO.; our work shows no evidence for this species. The sulfinyl radicals are suggested to result from a direct reaction between thiyl radicals and molecular oxygen. This reaction results in the cleavage of the dioxygen bond. 相似文献
9.
R A Kloner 《Free radical biology & medicine》1988,4(1):5-7
10.
D N Rao L Harman A Motten J Schreiber R P Mason 《Archives of biochemistry and biophysics》1987,255(2):419-427
Nitrofurantoin, misonidazole, and metronidazole were reduced to their corresponding nitro anion radicals by ascorbate in anaerobic solutions at high pH. The nitrofurantoin anion radical could be detected at neutral pH. In neutral solutions, the nitro anion radicals of misonidazole and metronidazole were too unstable to be observed by electron spin resonance spectroscopy. At neutral pH, solutions containing ascorbate, nitrofurantoin, or misonidazole consumed oxygen. The addition of superoxide dismutase, catalase, or both superoxide dismutase and catalase decreased the rate of oxygen consumption. These results show that nitro anion radicals are formed by reduction with ascorbate, and superoxide anion radical and hydrogen peroxide are produced by reactions of these radicals with oxygen. 相似文献
11.
Reperfusion injury 总被引:9,自引:0,他引:9
Several lines of evidence point to a major role of oxygen free radicals in the pathogenesis of cell death or dysfunction in a variety of disease processes. Recent studies from this as well as other laboratories have demonstrated that oxygen free radicals play a major role in the pathogenesis of post-ischemic reperfusion injury in the heart. We have recently developed methods for direct measurement of radical species and/or specific byproducts of radical injury. Timely administration of oxygen radical scavengers reduced the quantity of free radicals generated following reperfusion and in addition improved recovery of post-ischemic ventricular function and metabolism. In a regionally ischemic model the free radical scavenger recombinant human superoxide dismutase also administered at the time of reflow was shown to limit infarct size. In this article we review the biophysical and molecular mechanisms of oxygen free radical generation that are viewed as contributing to post-ischemic reperfusion injury. We also discuss the mechanisms by which the body defends against free radical attack and the interrelationships of free radical injury to other mechanisms of tissue injury. 相似文献
12.
Samples of purple lipoxygenase prepared by addition of either 13-hydroperoxy-9,11-octadecadienoic acid or linoleic acid and oxygen to ferric lipoxygenase contain pentadienyl and/or peroxyl radicals. The radicals are identified by the g values and hyperfine splitting parameters of natural abundance and isotopically enriched samples. The line shapes of their EPR spectra suggest the radicals are conformationally constrained when compared to spectra of the same radicals generated in frozen linoleic acid. Further, the EPR spectra are unusually difficult to saturate. The radicals are stable in buffered aqueous solution at 4 degrees C for several minutes. All of this implies that these species are bound to the enzyme, possibly in proximity to the iron. Only peroxyl radical is seen when the purple enzyme is generated with either hydroperoxide or linoleic acid in O2-saturated solutions. Addition of natural abundance hydroperoxide under 17O-enriched O2 leads to the 17O-enriched peroxyl radical, while the opposite labeling results in the natural abundance peroxyl radical, demonstrating the exchange of oxygen. Both radicals are detected in samples of purple lipoxygenase prepared with either linoleic acid or hydroperoxide under air. Addition of the hydroperoxide in the absence of oxygen favors the pentadienyl radical. We propose that addition of either linoleic acid or hydroperoxide to ferric lipoxygenase leads to multiple mechanistically connected enzyme complexes, including those with (hydro)peroxide, peroxide, peroxyl radical, pentadienyl radical, and linoleic acid bound. This hypothesis is essentially identical with the proposed radical mechanism of oxygenation of polyunsaturated fatty acids by lipoxygenase. 相似文献
13.
T Igarashi K Sakurai T Oi H Obara H Ohya H Kamada 《Free radical biology & medicine》1999,26(9-10):1339-1345
Free radicals are well-established transient intermediates in chemical and biological processes. Singlet oxygen, though not a free radical, is also a fairly common reactive chemical species. It is rare that singlet oxygen is studied with the electron spin resonance (ESR) technique in biological systems, because there are few suitable detecting agents. We have recently researched some semiquinone radicals. Specifically, our focus has been on bipyrazole derivatives, which slowly convert to semiquinone radicals in DMSO solution in the presence of potassium tert-butoxide and oxygen. These bipyrazole derivatives are dimers of 3-methyl-1-phenyl-2-pyrazolin-5-one and have anti-ischemic activities and free radical scavenging properties. In this work, we synthesized a new bipyrazole derivative, 4,4'-bis(1p-carboxyphenyl-3-methyl-5-hydroxyl)-pyrazole, DRD156. The resulting semiquinone radical, formed by reaction with singlet oxygen, was characterized by ESR spectroscopy. DRD156 gave no ESR signals from hydroxyl radical, superoxide, and hydrogen peroxide. DRD156, though, gives an ESR response with hypochlorite. This agent, nevertheless, has a much higher ability to detect singlet oxygen than traditional agents with the ESR technique. 相似文献
14.
巨噬细胞产生NO.和O_2~-自由基的分子机理 总被引:2,自引:0,他引:2
建立了用顺磁共振(ESR)和化学发光技术测定巨噬细胞产生NO和氧自由基的方法.捕捉到了巨噬细胞受佛波酯刺激产生的NO.和O-2自由基.测定了在不同浓度L-精氨酸存在时佛波酯刺激后巨噬细胞产生的NO自由基.研究了巨噬细胞产生的NO和氧自由基的分子机理.结果表明巨噬细胞不仅产生氧自由基而且产生NO自由基.NADPH氧化酶产生氧自由基的部位位于巨噬细胞膜的外侧.NO合成酶活化产生NO自由基比NADPH氧化酶活化产生氧自由基晚几分钟. 相似文献
15.
Oxygen radicals in the adult respiratory distress syndrome, in myocardial ischemia and reperfusion injury, and in cerebral vascular damage 总被引:4,自引:0,他引:4
Recent work suggests that oxygen radicals may be important mediators of damage in a wide variety of pathologic conditions. In this review we consider the evidence supporting the participation of oxygen radicals in the adult respiratory distress syndrome, in ischemia reperfusion injury in the myocardium, and in cerebral vascular injury in acute hypertension and traumatic brain injury. In the adult respiratory distress syndrome there is active sequestration of polymorphonuclear neutrophils in the pulmonary vascular system. There is evidence that activation of these neutrophils results in the production of oxygen radicals which injure the capillary membrane and increase permeability, leading to progressive hypoxia and decreased lung compliance which are hallmarks of the syndrome. In acute arterial hypertension or experimental brain injury oxygen radicals are important mediators of vascular damage. The metabolism of arachidonic acid is the source of oxygen free radical production in these conditions. In myocardial ischemia and reperfusion injury, the ischemic myocyte is "primed" for free radical production. With reperfusion and reintroduction of molecular oxygen there is a burst of oxygen radical production resulting in extensive tissue destruction. Myocardial ischemia--reperfusion injury shares in common with the other two syndromes activation of the arachidonic acid cascade and acute inflammation. Thus it would appear that the generation of toxic oxygen species may represent a final common pathway of tissue destruction in several pathophysiologic states. 相似文献
16.
Recently, novel applications of the nitroxide radicals have been proposed as antioxidant and anti-cancer agents. In view of the significance of nitroxide radical as a potential pharmaceutical agent for various applications in biological systems, it will be important to investigate further whether nitroxide radicals have a neurotoxicity or not. Blood-brain barrier permeable nitroxide radical, 3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (PCAM; five-membered ring nitroxide radical) would provide us more important information to explore the neuronal excitotoxicity of nitroxide radicals on the central nervous system. Every rat injected with PCAM showed limbic seizure with secondary generalization. PCAM administration resulted in neuronal cell loss in CA1 area, which is closely associated with the neurotoxicity of endogenous glutamate and nitroxide itself. More detailed studies on their possible toxicity of nitroxide radicals will be needed before the prospect of moving nitroxide from the experimental to the clinical arena when nitroxide radicals would be used for CNS disease in future. 相似文献
17.
Generation of singlet oxygen is first investigated in the decomposition of polyunsaturated lipid peroxide, alpha-linolenic acid hydroperoxide (LAOOH), by heme-proteins such as cytochrome c and lactoperoxidase. Chemiluminescence and electron spin resonance methods are used to confirm the singlet oxygen generation and quantify its yield. Decomposition products of LAOOH are characterized by HPLC-ESI-MS, which suggests that singlet oxygen is produced via the decomposition of a linear tetraoxide intermediate (Russell's mechanism). Free radicals formed in the decomposition are also identified by the electron spin resonance technique, and the results show that peroxyl, alkyl, and epoxyalkyl radicals are involved. The changes of cytochrome c and lactoperoxidase in the reaction are monitored by UV-visible spectroscopy, revealing the action of a monoelectronic and two-electronic oxidation for cytochrome c and lactoperoxidase, respectively. These results suggest that cytochrome c causes a homolytic reaction of LAOOH, generating alkoxyl radical and then peroxyl radical, which in turn releases singlet oxygen following the Russell mechanism, whereas lactoperoxidase leads to a heterolytic reaction of LAOOH, and the resulting ferryl porphyryl radical of lactoperoxidase abstracts the hydrogen atom from LAOOH to give peroxyl radical and then singlet oxygen. This observation would be important for a better understanding of the damage mechanism of cell membrane or lipoprotein by singlet oxygen and various radicals generated in the peroxidation and decomposition of lipids induced by heme-proteins. 相似文献
18.
H van Jaarsveld A J Groenewald G M Potgieter S P Barnard W J Vermaak H C Barnard 《Enzyme》1988,39(1):8-16
Recent evidence suggests that free oxygen radicals are produced by ischaemic tissues, accounting for at least part of the damage that results. These free oxygen radicals are produced by xanthine oxidase, amongst others, and removed by scavenger enzymes (catalase, superoxide dismutase and glutathione peroxidase) and anti-oxidants. As mitochondria are oxygen-utilising organelles, they are capable of producing free oxygen radicals. Our results indicate that the removal of free oxygen radicals are not diminished during ischaemia, but the activity of the free oxygen radical generator, xanthine oxidase, is increased. This could lead to an increased superoxide anion concentration. 相似文献
19.
《Redox report : communications in free radical research》2013,18(5):255-261
AbstractA study of the involvement of free oxygen radicals in trapping and digestion of insects by carnivorous plants was the main goal of the present investigation. We showed that the generation of oxygen free radicals by pitcher fluid of Nepenthes is the first step of the digestion process, as seen by EPR spin trapping assay and gel-electrophoresis. The EPR spectrum of N. gracilis fluid in the presence of DMPO spin trap showed the superposition of the hydroxyl radical spin adduct signal and of the ascorbyl radical signal. Catalase addition decreased the generation of hydroxyl radicals showing that hydroxyl radicals are generated from hydrogen peroxide, which can be derived from superoxide radicals. Gel-electrophoresis data showed that myosin, an abundant protein component of insects, can be rapidly broken down by free radicals and protease inhibitors do not inhibit this process. Addition of myoglobin to the pitcher plant fluid decreased the concentration of detectable radicals. Based on these observations, we conclude that oxygen free radicals produced by the pitcher plant aid in the digestion of the insect prey. 相似文献
20.
The oxygen effect in radiation inactivation of DNA and enzymes 总被引:1,自引:0,他引:1
M Quintiliani 《International journal of radiation biology and related studies in physics, chemistry, and medicine》1986,50(4):573-594
A survey is made of literature data dealing with the influence of oxygen on radiation effects in biologically active DNA and enzymes irradiated extracellularly. There is evidence that oxygen takes part in physico-chemical events, directly or indirectly produced by radiation in several ways: from scavenging reducing primary water radicals to reacting directly with macromolecular radical sites. There is evidence that radiation-induced secondary radicals, originating from a variety of low molecular weight biomolecules, can react with DNA and enzymes in their native state, and produce inactivation. By reaction with oxygen secondary radicals become peroxidized and in this form are generally more harmful to biological macromolecules. There are indications that thiol peroxy radicals can also act in the same way. Possible implications for the oxygen effect observed in vivo are discussed. 相似文献