Freie Radikale & Oxidativer Stress
Aktuelle wissenschaftliche Studien | 81-100
81: FEBS Lett. 2005 Dec 19;579(30):6909-13. Epub 2005 Dec 1.
Related Articles,
Links
Free radicals-mediated damage in transmitochondrial cells harboring the T14487C mutation in the ND6 gene of mtDNA.
Gonzalo R, Garcia-Arumi E, Llige D, Marti R, Solano A, Montoya J, Arenas J, Andreu AL.
Centre d'Investigacions en Bioquimica i Biologia Molecular, Hospital Vall d'Hebron, Passeig Vall d'Hebron 119-129, 08035 Barcelona, Spain.
We have studied the production of reactive oxygen species (ROS) in transmitochondrial cells, harboring homoplasmic levels of the T14487C mtDNA mutation in the ND6 gene of mitochondrial DNA (mtDNA). Previous work has shown that this mutation causes complex I deficiency. Here, we show that this mutation causes an overproduction of ROS leading to an increase in the oxidation of lipids and mtDNA without modification of antioxidant enzyme activities. We suggest that mutations in mtDNA affecting complex I activity may result in oxidative cellular damage, and reinforce the possible role of ROS-mediated mechanisms participating in some mtDNA-related disorders.
Publication Types:
PMID: 16337195 [PubMed - indexed for MEDLINE]
82: Biol Trace Elem Res. 2005 Winter;108(1-3):43-52.
Related Articles,
Links
Plasma values of oxidants and antioxidants in acute brain hemorrhage: role of free radicals in the development of brain injury.
Aygul R, Demircan B, Erdem F, Ulvi H, Yildirim A, Demirbas F.
Department of Neurology, Medical Faculty, Ataturk University, Erzurum, Turkey.
The levels of oxidants xanthine oxidase (XO), nitric oxide (NO), and malondialdehyde (MDA) and of the antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and glutathione reductase (GRD) were determined in plasma within 24 h after onset of hemorrhagic stroke in 17 patients (9 men and 8 women, aged 60.7+/-11.5 yr) and in 20 healthy controls (12 men and 8 women, aged 62.5+/-8.3 yr). Compared to controls, the plasma SOD and total superoxide scavenger activities (TSSA) were significantly lower and the NO levels were significantly higher among the stroke patients. XO showed a slight, nonsignificant increase in the patients, but the levels of MDA, NSSA, GRD, and GSH-Px did not show any significant differences between the two groups. The hemorrhage volume was negatively correlated with the initial score of the Glasgow Coma Scale and a positive correlation with lethal outcome, but it did not correlate significantly with any of the measured parameters. The results suggest that free radicals might play a role in the development of brain injury following brain hemorrhage.
Publication Types:
PMID: 16327058 [PubMed - indexed for MEDLINE]
83: J Neurochem. 2006 Jan;96(1):1-13. Epub 2005 Nov 23.
Related Articles,
Links
Amyloid precursor protein-mediated free radicals and oxidative damage: implications for the development and progression of Alzheimer's disease.
Reddy PH.
Neurogenetics Laboratory, Neurological Sciences Institute, Oregon Health & Science University, Beaverton, Oregon 97006, USA. reddyh@oshu.edu
Alzheimer's disease (AD) is a late-onset dementia that is characterized by the loss of memory and an impairment of multiple cognitive functions. Advancements in molecular, cellular, and animal model studies have revealed that the formation of amyloid beta (Abeta) and other derivatives of the amyloid precursor protein (APP) are key factors in cellular changes in the AD brain, including the generation of free radicals, oxidative damage, and inflammation. Recent molecular, cellular, and gene expression studies have revealed that Abeta enters mitochondria, induces the generation of free radicals, and leads to oxidative damage in post-mortem brain neurons from AD patients and in brain neurons from cell models and transgenic mouse models of AD. In the last three decades, tremendous progress has been made in mitochondrial research and has provided significant findings to link mitochondrial oxidative damage and neurodegenerative diseases such as AD. Researchers in the AD field are beginning to recognize the possible involvement of a mutant APP and its derivatives in causing mitochondrial oxidative damage in AD. This article summarizes the latest research findings on the generation of free radicals in mitochondria and provides a possible model that links Abeta proteins, the generation of free radicals, and oxidative damage in AD development and progression.
Publication Types:
PMID: 16305625 [PubMed - indexed for MEDLINE]
84: J Perinat Neonatal Nurs. 2005 Oct-Dec;19(4):298-300.
Related Articles,
Links
Free radicals in perinatal and neonatal care, part 1: the basics.
Blackburn S.
Department of Family and Child Nursing, University of Washington, Seattle, WA, USA.
PMID: 16292131 [PubMed - indexed for MEDLINE]
85: FEBS Lett. 2005 Nov 21;579(28):6511-7. Epub 2005 Nov 2.
Related Articles,
Links
Rapid rates of newly synthesized mitochondrial protein degradation are significantly affected by the generation of mitochondrial free radicals.
Basoah A, Matthews PM, Morten KJ.
Department of Clinical Neurology, Neurosciences Group, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK.
Exposure of biological material to high levels of free radicals causes extensive cellular damage. Reactive oxygen species (ROS) generated by mitochondria have been associated with a variety of diseases and aging. We investigated the effect of low-level mitochondrial ROS production on newly synthesized mitochondrial proteins which are potentially vulnerable to mitochondrial ROS due to their location and unfolded state. We show that elevated mitochondrial ROS increases the degradation of newly synthesized mitochondrial proteins with some proteins more sensitive than others. In the long term reduced assembly of mitochondrial complexes would affect mitochondrial function and may trigger a vicious cycle of mitochondrial ROS production.
Publication Types:
PMID: 16289094 [PubMed - indexed for MEDLINE]
86: Int J Biol Markers. 2005 Jul-Sep;20(3):169-76.
Related Articles,
Links
Comment in:
Plant-based diet, serum fatty acid profile, and free radicals in postmenopausal women: the diet and androgens (DIANA) randomized trial.
Colombo C, Muti P, Pala V, Cavalleri A, Venturelli E, Locardi M, Berrino F, Secreto G.
Hormone Research Laboratory, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
High calorie and fat consumption and the production of free radicals are two major mechanistic pathways between diet and disease. In this study we evaluated the effect of a plant-based diet poor in animal fat and rich in (n-3) fatty acids on fatty acids of serum phospholipids and on the production of reactive oxygen metabolites (ROMs). One hundred and four healthy female postmenopausal volunteers were recruited and randomized to a dietary intervention or a control group. Dietary intervention included a program of food education and biweekly common meals for 18 weeks. When the intervention and control groups were compared, it was seen that dietary intervention resulted in a significant reduction of saturated fatty acids (-1.5%) and a significant increase in (n-3) fatty acids (+20.6%), in particular docosahexaenoic acid (+24.8%). We observed that arachidonic acid decreased (-7.7%), while (n-6) fatty acids did not, and the (n-3)/(n-6) polyunsaturated ratio increased significantly (+24.1%). As expected, ROMs decreased significantly in the intervention group (-6%). The results indicated that a plant-based diet can improve the serum fatty acid profile and decrease ROMs production. These results suggest that a plant-based diet may reduce the body's exposure to oxidative stress.
Publication Types:
PMID: 16240844 [PubMed - indexed for MEDLINE]
87: Curr Pharm Des. 2005;11(24):3141-58.
Related Articles,
Links
Role of free radicals in sepsis: antioxidant therapy.
Victor VM, Rocha M, Esplugues JV, De la Fuente M.
Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III-Universidad de Valencia (CNIC-UVEG), Departamento de Farmacología, Facultad de Medicina, Avda Blasco Ibanez, 46010 Valencia, Spain. vmvictor@cnic.es
Severe sepsis leading to shock is the principal cause of death in intensive care units. It is a systemic inflammatory response caused by excessive secretion of pro-inflammatory mediators, such as tumor necrosis factor-alpha (TNFalpha) and reactive oxygen species (ROS), mainly induced by endotoxin (a major component of the Gram-negative bacterial outer membrane). Immune cells use ROS in order to support their functions and need adequate levels of antioxidant defenses to avoid harmful effects of an excessive ROS production. In addition, nitric oxide (NO) is thought to play a key role in the pathogenesis of sepsis and in the development of multiple organ failure. This article discusses the toxic effects of endotoxin, paying particular attention to cardiovascular damage. It continues by analysing the mechanism by which endotoxin is recognized by specific cells of the immune system, and the pathway leading to nuclear factor-kappaB (NF-kappaB) activation and pro-inflammatory gene transcription. In relation to this process, this review focuses on the involvement of reactive oxygen and nitrogen species. Finally, the protective role of antioxidants against homeostatic disturbances such as those caused by endotoxin toxicity, their potential clinical use and the effects on the redox state of the immune cells is discussed.
Publication Types:
PMID: 16178750 [PubMed - indexed for MEDLINE]
88: Mol Cell Biochem. 2005 Sep;277(1-2):89-99.
Related Articles,
Links
Different antioxidants status, total antioxidant power and free radicals in essential hypertension.
Kashyap MK, Yadav V, Sherawat BS, Jain S, Kumari S, Khullar M, Sharma PC, Nath R.
Department of Experimental Medicine and Biotechnology, PGIMER, Chandigarh, India. mkashyap@uiuc.edu
Hypertension is a multi-factorial process, prevalent in developed as well as in developing countries. Different antioxidants and free radicals play an important role in cardiovascular system. In present study, total antioxidant power in terms of FRAP (ferric reducing activity of plasma), free radicals and different antioxidants have been studied in essential hypertensives (n = 50) and normal subjects (n = 50). Levels of total cholesterol, low-density lipids-cholesterol, malonialdehyde, very low-density lipids (VLDL), uric acid, plasma homocysteine and low-density lipids (LDL), were significantly higher in hypertensives as compared to normotensive. HDL-cholesterol, SOD, GPx, reduced glutahione, total glutathione, oxidized glutathione, total thiols, protein thiols, non protein thiols, RNI, total antioxidant power, vitamin A, ascorbic acid and glutahione-S-transferase (GST) were decreased significantly in normotensive. We observed significantly low nitric oxide levels in hypertensive patients. No correlation was observed between severity of disease and plasma nitric oxide levels. There was a significant decrease in plasma FRAP value in essential hypertensives as compared to normotensive controls, which showed a negative correlation with diastolic blood pressure. In conclusion, our study revealed that there was a consistent significant difference between essential hypertensives versus controls with respect to most of the parameters. These complex changes are consistent in the view that essential hypertension is associated with an abnormal level of antioxidant status compared to normal response to oxidative stress or both.
Publication Types:
PMID: 16132719 [PubMed - indexed for MEDLINE]
89: J Am Chem Soc. 2005 Aug 17;127(32):11220-1.
Related Articles,
Links
Time-resolved detection of melanin free radicals quenching reactive oxygen species.
Seagle BL, Rezai KA, Gasyna EM, Kobori Y, Rezaei KA, Norris JR Jr.
Department of Chemistry, University of Chicago, 5735 South Ellis Avenue, Chicago, Illinois 60637, USA.
Melanin, a ubiquitous, heterogeneous biological polymer composed of many different monomers, contains a population of stationary, intrinsic semiquinone-like radicals. Additional extrinsic semiquinone-like radicals are reversibly photogenerated with visible or UV irradiation. The free radical chemistry of melanin is complex and not well characterized, especially the photochemistry of melanin in the presence of oxygen. To determine directly how melanin reacts in the presence of oxygen, time-resolved electron paramagnetic resonance (TREPR) spectroscopy was used to examine melanin free radical chemistry in human retinal pigment epithelium (RPE) cells under aerobic and anaerobic conditions. A TREPR difference spectrum was used to explore the nature of melanin chemistry in the presence of oxygen. The position and symmetrical line shape of the TREPR three-dimensional difference spectrum shows that when reactive oxygen species (ROS) are scavenged, only one of the two or more chemically different melanin free radical species participates in ROS scavenging. This protective melanin radical species exists in both the extrinsic and intrinsic populations of melanin free radicals, allowing melanin to protect the RPE from toxic species in both the light and dark.
Publication Types:
PMID: 16089432 [PubMed - indexed for MEDLINE]
90: Curr Alzheimer Res. 2005 Apr;2(2):191-6.
Related Articles,
Links
Extracellular superoxide dismutase (EC-SOD) quenches free radicals and attenuates age-related cognitive decline: opportunities for novel drug development in aging.
Levin ED.
Department of Psychiatry and Behavioral Sciences, Box #3412, Duke University Medical Center, Durham, NC 27710, USA. edlevin@duke.edu
Superoxide dismutase (SOD) is one of the most effective mechanisms in physiology for inactivating reactive oxygen species. Elevated SOD activity can be therapeutically useful by protecting against oxidative stress-induced neurotoxicity. Acutely increased extracellular-SOD (EC-SOD) activity protects against neurobehavioral impairment caused by acute ischemia. Chronically increased EC-SOD activity may also be therapeutically useful by protecting against chronic oxidative stress-induced neurobehavioral damage that accumulates during the aging process. We have found that mice with genetic overexpression of EC-SOD do not show the aging-induced decline in learning and memory that control, wild type mice show. From 14-22 months of age, the EC-SOD overexpressing mice have significantly better spatial learning working memory function than that of controls. This effect is specific to the aging period. Young adult EC-SOD overexpressing mice do not have better learning and memory function than controls. The beneficial effects of increased EC-SOD activity with aging may be achieved without risk of impairment during younger ages by chronically administering EC-SOD mimetics from mature adulthood into the aging period. Novel EC-SOD mimetics may be useful in attenuating aging-induced cognitive impairments and other aspects of physiological decline with aging.
Publication Types:
PMID: 15974918 [PubMed - indexed for MEDLINE]
91: Toxicology. 2005 Jun 1;210(2-3):235-45.
Related Articles,
Links
Cytotoxic effect of formaldehyde with free radicals via increment of cellular reactive oxygen species.
Saito Y, Nishio K, Yoshida Y, Niki E.
Human Stress Signal Research Center (HSSRC), National Institute of Advanced Industrial Science and Technology (AIST), 1-8-31 Midorigaoka, Ikeda, Osaka 563-8577, Japan. yoshiro-saito@aist.go.jp
It is well known that formaldehyde (HCHO) and reactive oxygen species (ROS), such as free radicals, are cytotoxic as well as potentially carcinogenic. Although the individual effects of these reactants on cells have been investigated, the cytotoxicity exerted by the coexistence of HCHO and reactive radicals is poorly understood. The present study using Jurkat cells demonstrated that the coexistence of HCHO with water-soluble radical initiator, 2,2'-azobis-[2-(2-imidazolin-2-yl)propane] dihydrochloride (AIPH) dramatically decreased cell viability, and that under such conditions scant cell death was observable induced by either of the reactants alone. Based on the results of phosphatidylserine exposure and caspase activation, this observed cell death, in fact, was apparently necrotic rather than apoptotic. To understand the mechanisms of the cell toxicity of HCHO and AIPH, we assessed two kinds of oxidative stress markers such as cellular glutathione (GSH) content and cellular ROS, and the DNA-protein cross-links, which formed as the result of HCHO treatment. A marked decrease in total cellular GSH was observed not only in the case of the coexistence conditions but also with AIPH alone. Dichlorodihydrofluorescein (DCF) assay revealed that cellular ROS were synergistically increased before cell death. The formation of DNA-protein cross-links was observed in the presence of HCHO and AIPH, and the extent was similar to HCHO alone. Co-incubation with semicarbazide, which inactivates HCHO, prevented this cell death induced by a combination of HCHO and AIPH. Semicarbazide also exhibited an inhibitory effect on the synergistic increment of cellular ROS and the formation of DNA-protein cross-links. These results suggest that the free radicals from AIPH induced GSH reduction, while HCHO resulted in the formation of DNA-protein cross-links, eventuating in a synergistic, incremental increase of cellular ROS and cell death brought about by this combination.
PMID: 15840437 [PubMed - indexed for MEDLINE]
92: J Hypertens. 2005 Apr;23(4):807-14.
Related Articles,
Links
Acute and chronic effects of free radicals on alpha1-adrenergic-induced vasoconstriction in mesenteric beds of spontaneously hypertensive rats.
Girouard H, de Champlain J.
Research Group on Autonomic Nervous System, Department of Physiology, Faculty of Medicine, University of Montreal, Montreal (Quebec), Canada.
OBJECTIVE: To determine whether free radicals participate in the increased sensitivity of the alpha-adrenergic pathway in mesenteric arteries from spontaneously hypertensive rats (SHRs). METHODS AND RESULTS: SHRs are characterized by a greater vasoconstriction (P < 0.001) in response to phenylephrine in isolated and perfused mesenteric arteries. Deferoxamine (DFX) produced a significant increase in the phenylephrine-induced vasoconstriction in isolated mesenteric beds from both SHRs (P < 0.001) and Wistar-Kyoto (WKY) rats (P < 0.05), but with a greater magnitude in SHRs (P < 0.01). Acutely, activation of the hypoxanthine-xanthine oxidase (HX-XO) system produced an endothelium- and NO-dependent vasoconstriction at low concentration (P < 0.01), followed by an endothelium-independent vasorelaxation at greater concentrations in phenylephrine-preconstricted mesenteric beds (P < 0.01). Catalase and SOD (P < 0.01) prevented this endothelium-dependent response, whereas the endothelium-independent vasorelaxation induced by HX-XO was blocked by catalase, SOD and DFX (P < 0.01). Chronic administration of a diet deficient in selenium and vitamin E decreased the glutathione peroxidase activity in erythrocytes and plasma from SHRs and WKY rats (P < 0.001). Moreover, the deficient diet significantly increased the sensitivity of mesenteric arteries to phenylephrine in SHRs (P < 0.001) and WKY rats (P < 0.05), whereas it decreased acetylcholine-induced vasodilatation in SHRs only (P < 0.05). The KCl-induced vasoconstriction in response to oxygen radicals was enhanced only in mesenteric bed from SHRs. CONCLUSION: Free radicals seem to potentiate the alpha-adrenergic pathway acutely in low concentrations and to sensitize this pathway chronically in SHRs. These observations may explain the potentiated response to alpha-adrenergic agonists observed in SHRs.
Publication Types:
PMID: 15775786 [PubMed - indexed for MEDLINE]
93: Neurosci Lett. 2005 Mar 29;377(2):130-5. Epub 2004 Dec 22.
Related Articles,
Links
Is brain dehydroepiandrosterone synthesis modulated by free radicals in mice?
Maayan R, Touati-Werner D, Ram E, Galdor M, Weizman A.
Laboratory of Biological Psychiatry, Felsenstein Medical Research Center, Petah Tikva 49100, Israel. rmayan@post.tau.ac.il
Dehydroepiandrosterone (DHEA) is a neurosteroid synthesized de novo in the brain, in addition to the periphery, modulating some membrane, ion-gated channel neurotransmitter receptors. P450-17alpha-hydroxylase activity converting pregnenolone to DHEA, has not yet been identified in the brain of rodents. Studies in brain-derived primary cultures and cell lines, suggest a possible alternative pathway for DHEA synthesis involving oxygenated hydroxyperoxides. We investigated DHEA synthesis in the brains of castrated male mice before and after treatment with N-acetylcysteine amide (AD4) (a newly developed brain penetrating antioxidant). We found a significant increase in brain DHEA level 24 h after castration, which was totally blocked by AD4. This blockade of castration-induced increased brain DHEA synthesis, supports the assumption that this synthesis may also be affected by free radicals. This is the first in vivo study indicating the possible existence of an in-brain oxidative stress-related pathway leading to brain DHEA production.
Publication Types:
PMID: 15740851 [PubMed - indexed for MEDLINE]
94: Expert Rev Cardiovasc Ther. 2005 Jan;3(1):159-71.
Related Articles,
Links
Free radicals and antioxidants in cardiovascular diseases.
Abrescia P, Golino P.
University of Naples Federico II, Department of General and Environmental Physiology, Via Mezzocannone 8, 80134 Naples, Italy. abrescia@biol.dgbm.unina.it
It has been demonstrated that redox homeostasis is important in the pathophysiology of several human diseases, including cardiovascular diseases. In this respect, genetic polymorphism, nutritional and environmental factors, age, lifestyle and physical activity may account for variable antioxidant defenses, which may be more or less effective at counteracting oxidative damage. Since accumulating oxidative damage may be associated with several pathologic conditions, including different cardiovascular diseases, prevention of oxidative stress appears to be a promising approach to improve such diseases. Exercise training, diets rich in antioxidants and a good control of blood glucose and lipid levels help to strengthen the physiologic antioxidant defense system, perhaps coupled to drugs capable of increasing the nitric oxide bioavailability and decreasing superoxide production. Within the next few years other therapeutic approaches will be available, such as gene therapy, which will prove to be even more effective but devoid of several important systemic side effects.
Publication Types:
PMID: 15723584 [PubMed - indexed for MEDLINE]
95: Intensive Crit Care Nurs. 2005 Feb;21(1):24-8.
Related Articles,
Links
A review of free radicals and antioxidants for critical care nurses.
Scheibmeir HD, Christensen K, Whitaker SH, Jegaethesan J, Clancy R, Pierce JD.
School of Nursing, University of Kansas, Kansas City, KS 66160-7504, USA.
In the critical care setting, nurses frequently care for patients with acute and chronic diseases that affect multiple body systems. Many of these medical conditions have been associated with an imbalance between oxidizing chemicals called free radicals and antioxidants. Free radical damage is now assumed to be a contributing factor in all major diseases. In order to provide the most current and comprehensive care, critical care nurses need to be well informed about how free radicals cause damage and the antioxidant compounds that neutralize their destructive effects. This article provides an overview of oxygen free radicals and antioxidants and how they impact different clinical illnesses familiar to critical care nurses.
Publication Types:
PMID: 15681214 [PubMed - indexed for MEDLINE]
96: Alcohol. 2004 Aug;34(1):49-58.
Related Articles,
Links
Role of free radicals in failure of fatty liver grafts caused by ethanol.
Zhong Z, Lemasters JJ.
Department of Cell and Developmental Biology, CB# 7090, 236 Taylor Hall, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Alcohol is associated with accidental deaths and suicides leading to organ donation, and hepatic steatosis is an important risk factor for initial poor function and failure of human liver grafts. Mechanisms of fatty graft failure are not fully understood, but increased oxidative stress may be a major factor. To characterize the role of free radical stress and the efficacy of antioxidant treatments in fatty liver graft injury, donors for orthotopic rat liver transplantation were treated chronically (3 or more weeks) and acutely (single dose) with ethanol. After transplantation, necrosis and alanine aminotransferase release were threefold to fourfold higher in recipients of fatty grafts from donors treated with ethanol either acutely or chronically compared with findings for recipients of grafts from untreated donors. Moreover, graft survival decreased from nearly 100% to less than 20%. Free radical adducts, as measured by electron spin resonance spectroscopy, were detected in the blood and bile of rats receiving fatty grafts caused by ethanol. Markers of lipid peroxidation also increased after transplantation. Destruction of Kupffer cells with gadolinium chloride decreased free radical production and improved graft survival. Leukocyte adhesion increased beginning early after implantation, and adherent white blood cells obtained from transplanted fatty livers produced the same free radical species as were detected in blood. Therefore, Kupffer cells and adherent white blood cells are important sources of free radicals. Free radicals not only damage fatty grafts directly but also lead to enhanced inflammation and disturbed microcirculation. Delivery of superoxide dismutase-1 and superoxide dismutase-2 genes, free radical-scavenging polyphenols, and antioxidant-containing Carolina Rinse solution reduced injury and improved survival of fatty grafts caused by ethanol. Taken together, these findings indicate that free radicals increase in fatty grafts after transplantation and play an important role in injury of fatty grafts obtained from ethanol-exposed donors. Treatment of fatty donor livers with antioxidants and free radical scavengers may thus be an effective clinical therapy to prevent failure of fatty grafts.
Publication Types:
PMID: 15670666 [PubMed - indexed for MEDLINE]
97: Free Radic Biol Med. 2005 Feb 15;38(4):411-25.
Related Articles,
Links
Prospects for the future: the role of free radicals in the treatment of stroke.
Schaller B.
Department of Neuroscience, Karolinska Institute, Retzius väg 8, S-17177 Stockholm, Sweden. neuroscience_imaging@hotmail.com
Studies using animal models of stroke have demonstrated that free radicals are highly reactive molecules generated predominantly during cellular respiration and normal metabolism. Imbalance between cellular production of free radicals and the ability of cells to defend against them is referred to as oxidative stress. After ischemic brain damage introduced by ischemic stroke or reperfusion, production of reactive oxygen species may increase, sometimes drastically, leading to tissue damage via several different cellular molecular pathways. The damage can become more widespread due to weakened cellular antioxidant defense systems after ischemic stroke. These experimental findings have important implications for the treatment of human cerebral ischemia. Agents directed at eliminating oxygen radicals must be administered before, or in the early stages of, reperfusion after ischemia. The therapeutic window seems to be narrow and limited to, at most, a few hours. Future research may clarify the current hypothesis that the accuracy of gene expression could account for the recovery of cellular function after ischemic stroke. This may open the window to the future use of drug combinations that may be rationally administered sequentially. If the phenomenon of ischemic tolerance plays a role in this concept is still a matter of debate.
Publication Types:
PMID: 15649644 [PubMed - indexed for MEDLINE]
98: Vnitr Lek. 2000 Jun;46(6):354-9.
Related Articles,
Links
[Effect of free radicals and antioxidant on the vascular wall]
[Article in Slovak]
Ginter E.
Ustav preventívnej a klinickej medicíny, Bratislava, Slovenská republika.
Free radicals pay an important role in the pathogenesis of atherosclerosis by their direct toxic action on the vascular endothelium as well as by antioxidant of low density lipoproteins (LDL) which subsequently increase their atherogenic potential. Natural antioxidants interrupt the chain-like increase of radicals and thus also the risk of oxidation stress. The majority of epidemiological data indicate that an increased intake of fruit, vegetables and other foods of plant origin reduces the risk of cardiovascular disease. On the other hand, several so far not completed long-term intervention studies with some antioxidant vitamins (e. g. vitamin E, beta-carotene) don't provide such unequivocal results. This indicated that fruit and vegetables contain other protective substances, other than vitamins, some which were identified so far. It is beyond doubt than even the intake of very large amounts of antioxidant vitamins does not ensure in humans exposed to the potent action of several traditional cardiovascular risk factors (hypertension, high LDL-cholesterol, smoking) unequivocal protection against ischaemic heart disease. On the other hand, it is probable that chronic antioxidant deficiency enhances the risk of development of pathological changes of the vascular system. So far the problem has yet been resolved whether to recommend within the framework of cardiovascular disease prevention to the public at large daily consumption of preparations containing natural antioxidants. The final word on the effectiveness of antioxidants in the prevention of cardiovascular disease will be provided by extensive intervention studies which are at present under way, the results of which will be available within the few years.
Publication Types:
PMID: 15645843 [PubMed - indexed for MEDLINE]
99: Vnitr Lek. 1999 May;45(5):319-24.
Related Articles,
Links
[Free radicals and extracorporeal renal replacement therapy]
[Article in Czech]
Eiselt J, Racek J, Opatrný K Jr.
I. interní klinika, LF UK a FN, Plzen.
Free radicals (FR), highly reactive substances with an unpaired electron in the outer orbital attack lipids, proteins and nucleic acids and alter the structure and function of these macromolecules. Against the negative effects of FR during evolution various defense mechanisms developed described comprehensively as antioxidant defense. Under physiological conditions in the organism equilibrium is established between free radical production and antioxidant defense factors. Extracorporeal renal replacement mechanisms can interfere in a negative way with this equilibrium. They provoke the formation of FR and at the same time they weaken the antioxidant defense e.g. by elimination of substances with antioxidant properties. Impairement of the equilibrium between FR production and antioxidant mechanisms to the disadvantage of antioxidant defense in patients with chronic renal failure was proved and is described as oxidative stress. Oxidative stress threatens dialyzed patients with serious clinical complications e.g. accelerated atherosclerosis, amyloidosis, haemolysis and the development of a state of chronic inflammation. Reduction of oxidative stress can be achieved by reducing FR production by using biocompatible dialyzation membranes, proper correction of acid-base disorders, by preventing an iron overload of the organism. The second approach is to foster the antioxidant defense by supplementation with antioxidants. Final recommendations as regards selection of the optimal dialyzation membrane, type of extracorporeal renal replacement and the amount and composition of antioxidant supplements have not yet been established and the problem is the subject of intense research.
Publication Types:
PMID: 15641259 [PubMed - indexed for MEDLINE]
100: Arch Biochem Biophys. 2005 Feb 15;434(2):299-305.
Related Articles,
Links
Surgical stress-induced alterations in retinoid metabolism in the small intestine: role of oxygen free radicals.
Prabhu R, Thomas S, Balasubramanian KA.
The Wellcome Trust Research Laboratory, Department of Gastrointestinal Sciences, Christian Medical College, Vellore 632004, India.
Oxidative stress in the small intestine can result in altered cell proliferation, migration, and differentiation of villus-crypt cells. Retinoid metabolism is recognized as an important mediator of cellular differentiation in the intestine. This study examined the effect of oxidative stress in retinoid metabolism in a surgical stress model. Surgical stress was performed by handling the intestine as done during laparotomy. Villus-crypt cells were isolated at different time periods and various retinoid concentrations in the cell homogenate and the retinoic acid forming enzymes were quantitated using HPLC. Surgical stress resulted in altered retinoid levels in various cell populations in the small intestine at 1 and 12h. The activity of alkaline phosphatase and retinal oxidase was also altered at these time points and all these changes were prevented by inhibiting superoxide generation using xanthine oxidase inhibitor, allopurinol. These studies suggest that alterations seen in enterocytes during surgical stress may be mediated by changes in retinoid metabolism.
Publication Types:
nach oben