Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:APRD00369 (ROS)
 19,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In vitro studies were carried out to determine if reactive oxygen species modified DNA molecules are the preferred antigen for anti-DNA antibodies found in SLE sera. Reactive oxygen species were generated by 254 nm irradiation of hydrogen peroxide. Single stranded breaks, decrease in Tm and modification of adenine (21.7%) and thymine (48%) were the major effects observed on native DNA fragments of 300 bp in length. The ROS-modified DNA showed increased binding with naturally occurring anti-DNA autoantibodies as compared to unmodified DNA fragments. These results were substantiated by competition ELISA. Measurement of binding with DNA fragments of varying size revealed considerably increased binding as the fragment size increased from 50 bp to 800 bp. The relative affinity of anti-DNA IgG for ROS-modified and native DNA fragments of 300 bp were in the order of 6.26 x 10(-8) M and 4.07 x 10(-8) M, respectively.
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PMID:Reactive oxygen species modified DNA fragments of varying size are the preferred antigen for human anti-DNA autoantibodies. 128 55

There is considerable evidence suggesting that reactive oxygen species (ROS; superoxide anion, hydrogen peroxide, hydroxyl radical, hypochlorous acid) are implicated in the pathogenesis of toxic, ischemic, and immunologically mediated glomerular injury. The capacity of glomerular cells, especially mesangial cells, to generate ROS in response to several stimuli suggests that these autacoids may play a role in models of glomerular injury that are independent of infiltrating polymorphonuclear leukocytes and monocytes. The mechanisms whereby ROS formation results in morphologic lesions and in modifications of glomerular permeability, blood flow, and filtration rate have been inferred from in vitro studies. They involve direct and indirect injury to resident cells (mesangiolysis) and glomerular basement membrane (in concert with metalloproteases) and alteration of both the release and binding of vasoactive substances, such as bioactive lipids (e.g., prostaglandin E2, prostacyclin, thromboxane), cytokines (e.g., tumor necrosis factor alpha), and possibly endothelium-derived relaxing factor. The importance of such processes appears to be modulated by the intrinsic antioxidant defenses of the glomeruli. Further studies are needed to address the role of ROS in human glomerular diseases.
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PMID:Reactive oxygen species as glomerular autacoids. 160 Jan 28

Trypanosomiasis (whether African sleeping sickness, or American Chaga's disease) is caused by an infection with a protozoan parasite, i.e. the trypanosome. This carries fatal sequences in the untreated host. Currently available chemotherapeutic drugs (some of which cure by involving reactive oxygen species (ROS] are not optimally adequate. They are toxic as well, and may also be carcinogenic. It is therefore desirable to devise better chemotherapeutic regimens. ROS destroy the parasite, but excess ROS damage host tissue and are potentially carcinogenic. Alpha-difluoromethylornithine (DFMO) inhibits ornithine decarboxylase and so lowers the levels of spermine and spermidine. This singular effect in the parasite inhibits its multiplication, whereas in the host tissue it prevents carcinogenesis by preventing cell proliferation. Thus, combination of ROS-generating drugs with DFMO would be very effective against trypanosomiasis, and would be without cancer risk too. The combination is therefore advocated for chemotherapy of trypanosoma infections. This necessities experimental investigations specifically directed towards establishing the optimally efficacious combination of DFMO with the drugs.
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PMID:Towards more efficacious chemotherapy of trypanosomiasis: combination of alpha-difluoromethylornithine (DFMO) with reactive oxygen generating drugs. 178 20

The ability of native and oxidized lipids and lipoproteins to stimulate production of reactive oxygen species (ROS; superoxide and hydrogen peroxide) by human blood monocytes has been studied in vitro. Neither native human low density lipoprotein (LDL), 'altered' LDL (oxidized either by lipoxygenase, activated human monocytes or air) nor oxidized cholesterol had any significant effect on ROS production of monocytes. However, different oxidation products of a lipid emulsion (Lipofundin; largely consisting of linoleic acid oxidized either by lipoxygenase, Fe3+ or ultraviolet irradiation) greatly enhanced ROS production of monocytes. A hypothesis that activation of circulating leucocytes by oxidized fatty acids may generate oxidized plasma LDL, was tested in rabbits. Characteristics of LDL, separated from rabbit plasma 6 h after intravenous injection of an oxidized lipid emulsion, was compared to that of LDL isolated before the lipid treatment. Post-treatment LDL-fraction of plasma had increased lipid peroxide content and compared to the pretreatment LDL, caused a threefold increase in the incorporation of cholesterol into cultured (rat aortic) endothelial cells. The observed intense and lasting stimulation of monocytes by oxidized polyunsaturated fatty acids in vitro, and the generation of 'altered' LDL by these oxidized lipids in vivo suggests a mechanism by which atherogenic oxidized LDL could form in the circulation.
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PMID:Activation of human blood monocytes by oxidized polyunsaturated fatty acids: a possible mechanism for the generation of lipid peroxides in the circulation. 201 3

In attempts to substantiate the possible participation of reactive oxygen species, and the significance of the xanthine oxidase system in both post-ischaemic reperfusion necrosis of the island flap and distal necrosis of the pedicle flap, and to develop new pharmacological measures for salvaging flap necrosis, a series of experiments were made using an island flap model and a random-pattern flap model in rats. The results were as follows: (1) Epoxysuccinyl derivative (E-64c), allopurinol and L-SOD salvaged post-ischaemic reperfusion necrosis of the island flaps; (2) E-64c and allopurinol did not salvage anticipated necrosis of the distal region of random flaps but L-SOD did; (3) tissue SOD activity did not reflect the fate of the island flap, but did of the distal region of the random flap. These results demonstrated a possible involvement of ROS in both post-ischaemic necrosis of island flaps and distal necrosis of random flaps. However, xanthine oxidase was significant in producing ROS only in the former.
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PMID:Involvement of reactive oxygen species in post-ischaemic flap necrosis and its prevention by antioxidants. 201 99

The role of ischemia itself, calcium overload and of reactive oxygen species (ROC) in reperfusion injury of the heart was characterized from the physiological, biochemical and morphological point of view. Experiments were performed on isolated rat hearts (Langndorff preparation), perfused at constant pressure of 65 Torr and 37 degrees C. The effect of ischemia was studied on the model of 30 min normothermic global ischemia with consequent 30 min reperfusion. Calcium overload and damage by ROS were modelled by Ca(2+)-paradox (3 min Ca(2+)-depletion followed by 10 min Ca(2+)-repletion) and by intraaortal bolus application of ROS-generating system (H2O2 + FeSO4) respectively. Evaluation of functional and biochemical parameters revealed that the changes in electrical activity, accumulation of lactate and the loss in total adenine nucleotides content in heart tissue may be well applied to characterize the participation of the above mechanisms on total reperfusion damage to the heart. Histochemically detected different patterns of distribution of enzyme activities also allow to distinguish between alterations caused by different factors of reperfusion injury.
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PMID:Functional changes in isolated rat heart related to different factors of reperfusion damage. 202 45

We assessed the generation of reactive oxygen species (ROS: O2-, H2O2, OH . , chemiluminescence) by neutrophils and monocytes from six patients with infectious mononucleosis, ten patients with other viral diseases, and ten normal controls. Neutrophils from infectious mononucleosis patients showed markedly decreased generation of all reactive oxygen species, compared with the two control groups; this abnormality persisted for four to eight weeks after disease onset. Monocytes from these patients generated normal levels of ROS. Normal neutrophils incubated with T lymphocytes from infectious mononucleosis patients generated significantly less of each ROS than did those incubated with T cells from either control group. T cell-mediated suppression of ROS generation required both OKT4+ cells from infectious mononucleosis patients and OKT8+ cells from either patients or normals. We conclude that the generation of reaction oxygen species in neutrophils is suppressed in patients with infectious mononucleosis, at least in part, by interacting subsets of T lymphocytes.
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PMID:Decrease in generation of reactive oxygen species by neutrophils from patients with infectious mononucleosis: role of suppressor T lymphocytes. 609 19

Bleomycin-induced, 6-thioguanine-resistant, "non deletion" mutants pretreated with or without either TRIEN (triethylenetetramine), a superoxide dismutase (SOD) inhibitor, or TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl), a SOD mimic, were analyzed by polymerase chain reaction (PCR)-directed DNA sequencing in a Chinese hamster ovary (CHO) cell derivative, AS52. Among the 23 bleomycin-induced mutants, six have 3-bp 5'-TGA-3' deletions in the region of 366-371, five have single-base deletions, seven have base substitutions, three have insertions, and two have possible translocations. Among the 16 bleomycin-induced mutants pretreated with TRIEN, six have the 5'-TGA-3' deletion (366-371), two have single-base deletions, one has a 13-bp deletion, four have single-base substitutions, one has a double-base substitution, and two have insertions. Among the 17 bleomycin-induced mutants pretreated with TEMPOL, six have the same TGA deletions, two have single-base deletions, two have single-base insertions, four have single-base substitutions, one mutant has a 12-bp deletion, one has a 13-bp deletion, and one mutant shows no detectable change in its coding region in the DNA sequence. A possible shift from a ROS-mediated mutational spectrum to a spontaneous mutational spectrum by TRIEN further indicates that reactive oxygen species play an important role in bleomycin mutagenesis in mammalian cells.
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PMID:Polymerase chain reaction-directed DNA sequencing of bleomycin-induced "nondeletion"-type, 6-thioguanine-resistant mutants in Chinese hamster ovary cell derivative AS52: effects of an inhibitor and a mimic of superoxide dismutase. 751 29

The antigenicity of native DNA modified with reactive oxygen species was examined. Goats were immunized with the modified polymer and the antibody response was estimated by direct binding and competition ELISA. The induced antibodies bound ROS-DNA and showed considerable binding to native DNA as well. Specificity analysis of the purified antibodies revealed the recognition of native B-, A- and allied conformations presented by various synthetic polynucleotides. The contribution of lysine residues to the immunochemical binding of purified IgG was investigated by modifying the free amino groups of lysine residues. The modification of lysine residues paralleled loss in IgG binding to ROS-DNA to the extent of 50%, suggesting that such residues might be involved in the antigen binding site of immunoglobulin molecule.
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PMID:Antigenic specificity of anti-ROS DNA antibodies: involvement of lysyl residues in antigen binding. 753 71

Reactive oxygen species (ROS: superoxide radical, O2.-; hydrogen peroxide, H2O2; hydroxyl radical, OH.), which arise from the univalent reduction of dioxygen are formed in mitochondria. We summarize here results which indicate that ROS, and also the radical nitrogen monoxide ('nitric oxide', NO), act as physiological modulators of some mitochondrial functions, but may also damage mitochondria. Hydrogen peroxide, which originates in mitochondria predominantly from the dismutation of superoxide, causes oxidation of mitochondrial pyridine nucleotides and thereby stimulates a specific Ca2+ release from intact mitochondria. This release is prevented by cyclosporin A (CSA). Hydrogen peroxide thus contributes to the maintenance of cellular Ca2+ homeostasis. A stimulation of mitochondrial ROS production followed by an enhanced Ca2+ release and re uptake (Ca2+ 'cycling') by mitochondria causes apoptosis and necrosis, and contributes to hypoxia/reperfusion injury. These kinds of cell injury can be attenuated at the mitochondrial level by CSA. When ROS are produced in excessive amounts in mitochondria nucleic acids, proteins, and lipids are extensively modified by oxidation. Physiological (sub-micromolar) concentrations of NO potently and reversibly deenergize mitochondria at oxygen tensions that prevail in cells by transiently binding to cytochrome oxidase. This is paralleled by mitochondrial Ca2+ release and uptake. Higher NO concentrations or prolonged exposure of cells to NO causes their death. It is concluded that ROS and NO are important physiological reactants in mitochondria and become toxic only when present in excessive amounts.
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PMID:Oxidants in mitochondria: from physiology to diseases. 759 28


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