Effects of catalase,peroxidase, superoxide dismutase and 10 scavengers of oxygen radicals in carrageenin edema and in adjuvant arthritis of rats

Summary Catalase, peroxidase and superoxide dismutase were found to inhibit significantly carrageenin edema and the primary phase of adjuvant arthritis in rats after i.v. injection. Heat-inactivated enzymes were as effective as the native enzymes. None of 10 scavengers of oxygen radicals inhibited the adjuvant arthritis at any time. Accordingly, no evidence for a participation of oxygen radicals in the secondary arthritis phase could be found, whereas a role of oxygen radicals in the primary arthritis phase and in carrageenin edema cannot be ruled out.     

N-Monomethyl-arginine and nicotinamide prevent streptozotocin-induced double strand DNA break formation in pancreatic rat islets

The impact of short term in vitro exposure to the diabetogenic drug streptozotocin on pancreatic islet glucose metabolism, insulin secretion, DNA fragmentation and cell viability, was studied. Streptozotocin impaired cell viability as well as insulin secretion and the oxidation of glucose. These effects were partially counteracted by inhibition of the inducible form of nitric oxide synthase with N-monomethyl-arginine and by scavenging oxygen free radicals with nicotinamide. Isolated islets underwent double strand DNA fragmentation after 24 h in culture. The degree of DNA breakdown was strongly enhanced by exposure of the islet DNA was obtained with N-monomethyl-arginine and nicotinamide. These data suggest that the generation of reactive oxygen and nitrogen species is involved in the deleterious action of streptozotocin on pancreatic islet tissue. A role for oxygen radicals generated during streptozotocin-induced islet cell damage as possible mediators of the expression of the inducible form of nitric oxide synthase and the scavenging action of nicotinamide on these radicals, is then proposed.     

Inhibition of firefly bioluminescence by scavengers of singlet oxygen,superoxide radicals and hydroxyl radicals

Summary The participation of highly energetic oxygen species in the ATP-induced bioluminescence of a firefly-extract has been investigated. The inhibition of light emission by a variety of specific scavengers suggests that singlet oxygen, superoxide radicals and hydroxyl radicals are important intermediates in the firefly bioluminescence reaction.Acknowledgments. I thank Prof. R. Bachofen, Institut für Allgemeine Botanik, Abteilung Mikrobiologie, Universität Zürich, Switzerland, in whose laboratory most of these studies have been performed, for his cooperativity. Financial support by the Deutsche Studienstiftung is gratefully acknowledged.     

Highly reactive oxygen species: detection, formation, and possible functions

The so-called reactive oxygen species (ROS) are defined as oxygen-containing species that are more reactive than O(2) itself, which include hydrogen peroxide and superoxide. Although these are quite stable, they may be converted in the presence of transition metal ions, such as Fe(II), to the highly reactive oxygen species (hROS). hROS may exist as free hydroxyl radicals (HO·), as bound ("crypto") radicals or as Fe(IV)-oxo (ferryl) species and the somewhat less reactive, non-radical species, singlet oxygen. This review outlines the processes by which hROS may be formed, their damaging potential, and the evidence that they might have signaling functions. Since our understanding of the formation and actions of hROS depends on reliable procedures for their detection, particular attention is given to procedures for hROS detection and quantitation and their applicability to in vivo studies.     

Alloxan acts as a prooxidant only under reducing conditions: influence of melatonin

Depending on the availability of suitable reducing agents, alloxan can be either a prooxidant or an antioxidant. Alloxan and its reduced derivative, dialuric acid, act as a redox couple, driven by reduced glutathione (GSH) or L-cysteine, generating in vitro in the presence of oxygen, both superoxide radical and hydrogen peroxide. The production of superoxide radicals was shown by the appearance of lucigenin chemiluminescence (CL) as well as by the generation of formazan from nitroblue tetrazolium (NBT). The lucigenin CL as well as the NBT reduction was inhibited by superoxide dismutase and partially by catalase. Melatonin inhibited alloxan-mediated CL. In contrast, in the absence of reducing agents, alloxan is a scavenger of superoxide radicals formed by other reactions. Because of the high content of reducing compounds in the cell (e.g. glutathione), it is suggested that alloxan acts in vivo mainly as a generator of reactive oxygen species. Received 9 November 1998; received after revision 15 January 1999; accepted 15 January 1999     

Biochemical events associated with rapid cellular damage during the oxygen- and calcium-paradoxes of the mammalian heart

The O2- and Ca2(+)-paradoxes have a number of features in common and it is suggested that release of cytosolic proteins in both paradoxes is initiated by the activation of a sarcolemma NAD(P)H dehydrogenase which can generate a transmembrane flow of H+ and e- and also oxygen radicals or redox cycling which damage ion channels and membrane proteins (phase I). Entry of Ca2+ through the damaged ion channels then exacerbates the damage by further activating this system, either directly or indirectly, and the redox cycling and/or oxygen radicals cause further damage to integral and cytoskeletal proteins of the sarcolemma resulting in microdamage to the integrity of the membrane (phase II) and the consequent release or exocytosis of cytoplasmic proteins and, under specialised conditions, the blebbing of the sarcolemma. The system may be primed either by removal of extracellular Ca2+ or by raising [Ca2+]i by a variety of measures, these two actions being synergistic. The system is initially activated in the Ca2(+)-paradox by the membrane perturbation associated with removal of extracellular Ca2+; prolonged anoxia in the metabolically active cardiac muscle causes a depletion of the ATP supply, particularly in the absence of glucose, and hence a rise in [Ca2+]i in phase I of the oxygen paradox with the consequent activation of the NAD(P)H oxidase at the sarcolemma. Oxygen radicals are probably generated in both paradoxes and may have a partial role in the genesis of damage, but are not essential in the Ca2(+)-paradox which continues under anoxia. Massive entry of Ca2+ also activates an intracellularly localised dehydrogenase (probably at the SR) which produces myofilament damage by redox cycling.     

Protein oxidation and 20S proteasome-dependent proteolysis in mammalian cells

The generation of reactive oxygen species is an inevitable aspect of aerobic life. In addition to being exposed to free radicals in the environment, aerobic organisms must also deal with oxygen radicals generated as byproducts of a number of physiological mechanisms - for example, by the mitochondrial and endoplasmic reticulum electron transport chains, and by cells of the immune system. Although most organisms are equipped with several lines of defense against oxidative stress, these defensive mechanisms are not 100% effective, and oxidatively modified forms of proteins accumulate during aging, and in many pathological conditions.?Oxidatively modified proteins can form large aggregates due to covalent cross-linking or increased surface hydrophobicity. Unless repaired or removed from cells, these oxidized proteins are often toxic and can threaten cell viability. Mammalian cells exhibit only limited direct repair mechanisms, and oxidatively damaged proteins appear to undergo selective proteolysis, primarily by the major cytosolic proteinase, the proteasome. Interestingly, it appears that the 20S 'core' proteasome conducts the recognition and elimination of oxidized proteins in an ATP-independent and ubiquitin-independent pathway. Received 31 May 2001; accepted 26 June 2001     

前列腺素E1与心肌保护研究进展

本文通过阐述前列腺素E1（PGE1）对缺血性心肌损伤及缺血再灌注过程中的抗炎作用，抑制血小板功能，减少氧自由基的产生，减轻钙超载等重要环节的影响，以及减轻细胞凋亡的调节作用等，揭示其在心肌保护中的作用机制。     

Inflammation and repeated infections in CGD: two sides of a coin

Chronic granulomatous disease (CGD) is an uncommon congenital immunodeficiency seen approximately in 1 of 250,000 individuals. It is caused by a profound defect in a burst of oxygen consumption that normally accompanies phagocytosis in all myeloid cells (neutrophils, eosinophils, monocytes, and macrophages). This “respiratory burst” involves the catalytic conversion of molecular oxygen to the oxygen free-radical superoxide, which in turn gives rise to hydrogen peroxide, hypochlorous acid, and hydroxyl radicals. These oxygen derivatives play a critical role in the killing of pathogenic bacteria and fungi. As a result of the failure to activate the respiratory burst in their phagocytes, the majority of CGD patients suffer from severe recurrent infections and rather unexplained prolonged inflammatory reactions that may result in granulomatous lesions. Both may cause severe organ dysfunction depending on the tissues involved. Preventive measures as well as rapid (invasive) diagnostic procedures are required to successfully treat CGD. Hematopoietic stem cell transplantation may be a serious option in some of the patients.     

Biochemical events associated with rapid cellular damage during the oxygen-and calcium-paradoxes of the mammalian heart

Summary The O_2– and Ca²⁺-paradoxes have a number of features in common and it is suggested that release of cytosolic proteins in both paradoxes is initiated by the activation of a sarcolemma NAD(P)H dehydrogenase which can generate a transmembrane flow of H⁺ and e^– and also oxygen radicals or recox cycling which damage ion channels and membrane proteins (phase I). Entry of Ca²⁺ through the damaged ion channels then exacerbates the damage by further activating this system, either directly or indirectly, and the redox cycling and/or oxygen radicals cause further damage to integral and cytoskeletal proteins of the sarcolemma resulting in microdamage to the integrity of the membrane (phase II) and the consequent release or exocytosis of cytoplasmic proteins and, under specialised condition, the blebbing of the sarcolemma. The system may be primed either by removal of extracellular Ca²⁺ or by raising [Ca²⁺]_i by a variety of measures, these two actions being synergistic. The system is initially activated in the Ca²⁺-paradox by the membrane perturbation associated with removal of extracellular Ca²⁺; prolonged anoxia in the metabolically active cardiac muscle causes a depletion of the ATP supply, particularly in the absence of glucose, and hence a rise in [Ca²⁺]_i in phase I of the oxygen paradox with the consequent activation of the NAD(P)H oxidase at the sarcolemma. Oxygen radicals are probably generated in both paradoxes and may have a partial role in the genesis of damage, but are not essential in the Ca²⁺-paradox which continues under anoxia. Massive entry of Ca²⁺ also activates an intracellularly localised dehydrogenase (probably at the SR) which produces myofilament damage by redox cycling.     

A new cellular function for peroxisomes related to oxygen free radicals?

Although in cell biology peroxisomes are still 'young' organelles, it is becoming increasingly clear that they are involved in important cellular functions. Recent results have indicated the presence of the metalloenzyme superoxide dismutase in peroxisomes and the production of superoxide free radicals (O2-) in these oxidative organelles. These findings, together with other experimental evidence, point towards the existence of new roles for peroxisomes in cellular active oxygen metabolism, something that has a potential impact in multiple areas of cell biology, particularly in biochemistry and biomedicine.     

Differential effect of silybin on the Fe2+-ADP and t-butyl hydroperoxide-induced microsomal lipid peroxidation

We have observed a differential effect of silybin dihemisuccinate on rat liver microsomal oxygen consumption and on lipid peroxidation induced by NADPH-Fe2+-ADP and t-butyl hydroperoxide. These results are ascribed to the antioxidant properties of the flavonoid. The differences observed in the effect of the catalysts may be a consequence of the different capacity of silybin to act as a scavenger of free radicals formed by NADPH-Fe2+-ADP or t-butyl hydroperoxide.     

Endothelial cells as part of a vascular oxygen-sensing system: hypoxia-induced release of autacoids

Higher developed organisms are equipped with many central and local control mechanisms, which enable an adequate blood and oxygen supply to tissues over a wide range of demands. Global adaptive responses include changes in the circulatory and ventilatory system as well as increases in the oxygen carrying capacity of the blood. At the level of the specialized organs there exist additional control systems for the regulation of local blood flow. Most systems make use of highly specialized cells which are able to sense the oxygen partial pressure of the transport medium, blood, and within the tissues. In the past years, it has been shown that the vascular endothelium lining the entire circulatory system can actively modulate the vascular tone and platelet functions by the release of autacoids, among them prostacyclin and endothelium-derived nitric oxide (EDRF). Recent experiments demonstrate that the release of EDRF is PO2-dependent, which suggests that endothelial cells may act as functional local oxygen sensors within the vascular system.     

Superoxide dismutase activity in the Spanish population

Summary Superoxide dismutase is an enzyme that catalyzes the dismutation of superoxide radicals to hydrogen peroxide and molecular oxygen. This superoxide radical is produced by all aerobic cells as a normal metabolic intermediate of molecular oxygen, and is dangerous for the cell because it induces the inactivation of various enzymes, lipid peroxidation and mutations. Superoxide dismutase can therefore be considered as a protective enzyme. The purpose of this work was to determine the level of superoxide dismutase activity in the Spanish population, and to study the factors that influence this activity. The superoxide dismutase activity of 2397 individuals was determined using the method described by Minami and Yoshikawa. The superoxide dismutase activity level in the adult Spanish population was found to be 4.16±0.89 Units/ml of blood. No significant variations with respect to sex were detected. But it was observed that the superoxide dismutase activity level was 9% higher in the young urban Spanish population.     

Superoxide dismutase activity in the Spanish population

Superoxide dismutase is an enzyme that catalyzes the dismutation of superoxide radicals to hydrogen peroxide and molecular oxygen. This superoxide radical is produced by all aerobic cells as a normal metabolic intermediate of molecular oxygen, and is dangerous for the cell because it induces the inactivation of various enzymes, lipid peroxidation and mutations. Superoxide dismutase can therefore be considered as a protective enzyme. The purpose of this work was to determine the level of superoxide dismutase activity in the Spanish population, and to study the factors that influence this activity. The superoxide dismutase activity of 2397 individuals was determined using the method described by Minami and Yoshikawa. The superoxide dismutase activity level in the adult Spanish population was found to be 4.16 +/- 0.89 Units/ml of blood. No significant variations with respect to sex were detected. But it was observed that the superoxide dismutase activity level was 9% higher in the young urban Spanish population.     

Effects of isoxazolyl-naphthoquinoneimines on growth and oxygen radical production in Trypanosoma cruzi and Crithidia fasciculata

Several 4-(aminomethylisoxazolyl)-1,2-naphthoquinones inhibited growth and DNA synthesis in Trypanosoma cruzi and stimulated O2 uptake and O2-. generation by the parasite epimastigotes and their mitochondrial and microsomal membranes; these results support the idea that oxygen radicals play a role in quinone toxicity. Maximal effects on respiration and O2-. generation were observed with antimycin-inhibited cells. Similar results as well as stimulation of H2O2 production were obtained with Crithidia fasciculata despite the presence of catalase in this organism.     

Differential effect of silybin on the Fe2+-ADP and t-butyl hydroperoxide-induced microsomal lipid peroxidation

Summary We have observed a differential effect of silybin dihemisuccinate on rat liver microsonal oxygen consumption and on lipid peroxidation induced by NADPH-Fe²⁺-ADP and t-butyl hydroperoxide. These results are ascribed to the antioxidant properties of the flavonoid. The differences observed in the effect of the catalysts may be a consequence of the different capacity of silybin to act as a scavenger of free radicals formed by NADPH-Fe²⁺-ADP or t-butyl hydroperoxide.This research was supported in part by grant B-2019-8412 from Dirección de Investigación y Bibliotecas, Universidad de Chile.     

Origines de la vie

Summary The synthesis of proteins, which contributed to the appearance of life, began on earth during the transition period of reduced earth-atmosphere into that containing free oxygen. Proteins resulted then from condensation between free radicals formed by the components of reduced earth-atmosphere and appeared during photochemical reactions. The actual synthesis of proteins, formed by active contribution of nucleic acids, presents the ways of improvement of the forms of life.

---

---

Varsovie.