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)

Twigs-dry leaves smoke condensate (TDS), as a source of clastogenic ROS and carcinogenic PAH, was investigated for its in vitro DNA-damaging effect in calf thymus DNA and human peripheral lymphocytes. An aqueous turmeric component--Aq.T--with an established antioxidant activity, was tested as a DNA protectant. TDS induced 13-fold damage to calf thymus DNA as judged by the emergence of a DNA damage specific, fluorescent product (em: 405 nm). Aq.T at 800 ng/microL extended 69% protection to calf thymus DNA and was comparable to the other protectants such as curcumin, BHA, vitamin E, SOD, and CAT. In human peripheral lymphocytes, TDS induced extensive DNA damage in comparison with the tumor promoter TPA, as judged by FADU. Aq.T at 300 ng/microL extended 90% protection to human lymphocyte DNA against TDS-induced damage, and was more effective than the other protectants--DABCO, D-mannitol, sodium benzoate, vitamin E (ROS quenchers), SOD, CAT (antioxidant enzymes), tannic acid, flufenamic acid, BHA, BHT, n-PG, curcumin and quercetin (antioxidants). Aq.T offered 65% protection to human lymphocyte DNA against TPA-induced damage and was comparable to SOD. The above results indicate that TDS induces substantial DNA damage in calf thymus DNA and human lymphocytes and Aq.T is an efficient protectant.
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PMID:DNA damage by smoke: protection by turmeric and other inhibitors of ROS. 193 45

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

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

We are constantly exposed, throughout life, to a wide variety of extrinsic and intrinsic agents which have the potential to damage cellular biomolecules, including DNA. Imperfections in cellular defence systems which protect against the fixation of DNA damage can lead to an accumulation of mutations which on their own, or in combination with other age-related changes, may contribute to ageing and the development of age-related pathologies. We have previously reported an increase in frequency of mutation with age in human lymphocytes taken from healthy males in the age groups, 35-39, 50-54 and 65-69 years. In this article we report on the findings of a recent study which was designed to assess whether the age-related increase in frequency of mutation was due to a decreased efficacy of the defence systems against ROS-induced DNA damage, namely antioxidant status and DNA repair processes, in the same study subjects. In vivo antioxidant status was assessed in each of the study subjects by measuring blood levels of; superoxide dismutase (SOD; EC 1.15.1.1), glutathione peroxidase (GPx; EC 1.11.1.9), catalase (EC 1.11.1.6), caeruloplasmin (CPL), uric acid and bilirubin. We did not find any statistically significant differences in the mean levels of these antioxidants between the three different age groups. To investigate the efficacy of DNA repair processes against ROS-induced DNA damage, an ELISA was used to quantitate DNA damage (as % single-stranded DNA; %SS-DNA) at various times following treatment of peripheral blood lymphocytes with hydrogen peroxide (H2O2). The results of this part of the study showed that in untreated lymphocytes, basal levels of %SS-DNA were significantly higher in individuals from the 65-69 years age group compared to the 35-39 years age group (p = 0.039, 0.0013; at 5% level of significance). No significant differences were found in H2O2 susceptibility with age immediately following treatment (p = 0.71, 1.00; at 5% level of significance) but a consistent and significant increase was observed in %SS-DNA remaining 90 min post-treatment in lymphocytes from subjects in the 65-69 years age group, compared to %SS-DNA present in lymphocytes from the 35-39 years age group (p = 0.013, 0.024; at 5% level of significance). The results of this study suggest that the age-related increase in frequency of mutations is not contributed to by alterations of in vivo antioxidant status with age but is by a decreased efficacy of the repair of ROS-induced DNA damage with age. The biological implications of somatic mutations in the ageing process are discussed.
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PMID:An investigation of antioxidant status, DNA repair capacity and mutation as a function of age in humans. 756 67

The most important electron acceptor in the biosphere is molecular oxygen which, by virtue of its bi-radical nature, readily accepts unpaired electrons to give rise to a series of partially reduced species collectively known as reduced (or 'reactive') oxygen species (ROS). These include superoxide (O.2-), hydrogen peroxide (H2O2), hydroxyl radical (HO.) and peroxyl (ROO.) and alkoxyl (RO.) radicals which may be involved in the initiation and propagation of free radical chain reactions and which are potentially highly damaging to cells. Mechanisms have evolved to restrict and control such processes, partly by compartmentation, and partly by antioxidant defences such as chain-breaking antioxidant compounds capable forming stable free radicals (e.g. ascorbate, alpha-tocopherol) and the evolution of enzyme systems (e.g. superoxide dismutase, catalase, peroxidases) that diminish the intracellular concentration of the ROS. Although some ROS perform useful functions, the production of ROS exceeding the ability of the organism to mount an antioxidant defence results in oxidative stress and the ensuing tissue damage may be involved in certain disease processes. Evidence that ROS are involved in primary pathological mechanisms is a feature mainly of extraneous physical or chemical perturbations of which radiation is perhaps the major contributor. One of the important radiation-induced free-radical species is the hydroxyl radical which indiscriminately attacks neighbouring molecules often at near diffusion-controlled rates. Hydroxyl radicals are generated by ionizing radiation either directly by oxidation of water, or indirectly by the formation of secondary partially ROS. These may be subsequently converted to hydroxyl radicals by further reduction ('activation') by metabolic processes in the cell. Secondary radiation injury is therefore influenced by the cellular antioxidant status and the amount and availability of activating mechanisms. The biological response to radiation may be modulated by alterations in factors affecting these secondary mechanisms of cellular injury.
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PMID:Free radicals in biology: oxidative stress and the effects of ionizing radiation. 790 6

Effects of a 20-membered macrocyclic bicopper complex and dioxotetramine copper complexes with linear or cyclic structure on the scavenging of ROS have been studied by ESR. The results indicated that all three copper coordinate complexes have SOD mimetic activity. The dioxotetramine copper complex with linear or cyclic structure did not have the scavenging effect on .OH produced by H2O2-Fe++ and 1O2 produced by the H2O2-NaOCl system, but the 20-membered macrocyclic bicopper complex was found to be capable of depressing the intensity of the ESR spectrum of the adduct formed from TMP and 1O2 as well as making the spectrum of DMPO-OH adduct splittings. This fact may suggest that there are interactions between the ROS and 20-membered macrocyclic ring in the SOD mimic.
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PMID:Effects of copper coordinate complexes on the scavenging of reactive oxygen species. 838 48

Central nervous system has a low antioxidative capacity, which is formed mainly by ascorbic acid. Therefore the cerebral tissue is threatened by the increased formation of free radicals and their metabolites (ROS--reactive oxygen species). ROS are formed such as in reperfusion phase after ischemia and in catecholamine metabolism, in oxidative stress due to hyperglycaemia. Polyunsaturated fatty acids (PUFA) are peroxidased by ROS; proteins and DNK are damaged as well. Free radicals are involved in etiology and pathogenesis of many CNS diseases, such as neuritis, Alzheimer disease, Parkinson disease, Huntington disease, aging and atherosclerosis of the brain, epilepsy, etc. During the antioxidant therapy it is necessary to consider the types of ROS, their origin and their mode of action, whether to administer hydrophilic or lipophilic antioxidants, eventually chelate agents, etc. Hydrophylic antioxidants are acting very soon after the administration, whereas the lipophilic ones reach their target tissues with a great delay. Therefore it is better to apply them preferentially like a prevention, if possible. Enzymatic antioxidants (SOD, GSPHx and catalase and others) are usually acting only for a short time. The methods of estimation of free radicals attacks are discussed as well their possible pathophysiological effects.
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PMID:[Free radicals in the central nervous system]. 866 12

Human mtDNA is a naked circular double-stranded DNA, which is continually exposed to the matrix that contains high levels of ROS and free radicals. High oxidative stress and a lack of proofreading during mtDNA replication and efficient DNA repair mechanisms in the mitochondria have rendered mtDNA extremely vulnerable to oxidative damage. More than one dozen large-scale deletions in mtDNA have been identified in various tissues of old humans. The 4,977-bp and 7,436-bp deletions are the most prevalent and abundant ones. The onset age of various mtDNA deletions varies greatly with tissues of each individual and type of deletion. In this and previous studies, we have demonstrated with PCR techniques that the frequency of occurrence and the proportion of the 4,977-bp and 7,436-bp deleted mtDNAs are significantly increased with the age of the human. The mtDNA deletions are not detectable in any tissues from young healthy subjects or blood cells from normal individuals of any age, which indicates that the deletions are generated and accumulated only in postmitotic cells upon aging. Moreover, we found that these mtDNA deletions occur more frequently and abundantly in tissues with high energy demand (e.g., muscle) as compared to those with low energy demand. On the other hand, we found that the amount of lipid peroxides measured as malondialdehyde and the activity of manganese-superoxide dismutase in the mitochondria exhibit an age-dependent increase in various human tissues. The lipid peroxide level in muscle was significantly higher than that in the other tissues. Moreover, we found a positive correlation between the proportion of the 4,977-bp deleted mtDNA and lipid peroxide content in the mitochondria of human tissues during aging. Muscle the tissue of high energy demand, was found to be more vulnerable to oxidative damage that lead to most abundant mtDNA deletions and lipid peroxidation among all the tissues examined. Taking these results together, we suggest that the enhanced generation of reactive oxygen species and lipid peroxides in the mitochondria during the aging process occur simultaneously with large-scale deletions and the other types of mutations in mtDNA, which are early molecular events and major contributory factors of human aging.
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PMID:Simultaneous increase of mitochondrial DNA deletions and lipid peroxidation in human aging. 868 24

This study has investigated the antioxidant capacity of human seminal plasma due to the presence of both high and low molecular weight antioxidant factors. Methods for the measurement of superoxide dismutase-like activity (SOD-like) and total antioxidant status (TAS) were automated, and had a within-run coefficient of variation of 7.3% for SOD-like activity and 4.8% for TAS. In 69 semen samples from unselected infertile men, SOD-like activity in seminal plasma ranged from 2 to 16 U/ml, with a mean of 6.9 +/- 2.8 U/ml. As SOD-like activity was correlated positively with levels of citric acid (p < 0.0001), zinc (p < 0.0002) and acid phosphatase activity (p < 0.0005), and there was no correlation with fructose levels, our results suggest that prostatic secretions are an important source of superoxide anion scavengers. Evaluation of SOD-like activity in infertile men with accessory sex gland infections (n = 12) showed significantly lower activity (p < 0.003) compared to values found in 12 infertile men without signs of infection. The values obtained for total antioxidant status (equivalent to the antioxidant capacity of alpha-tocopherol analogue) ranged from 1.7 to 2.3 mmol/L, with a mean of 2.1 +/- 0.1 (n = 40), reflecting the protective activity of ascorbate, urate and albumin, and to a very low extent of glutathione and taurine. The data obtained by TAS assay correlated with fructose, a major marker of vesicular secretion (p < 0.005), suggesting that low molecular weight components with antioxidant capacity derive partly from the seminal vesicles. The results indicate that the relative contribution of antioxidant defence systems capable of counteracting the deleterious action of superoxide anions, depends on the secretory activity of accessory sex glands and is independent of excessive ROS production due to increased oxidative stress.
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PMID:Superoxide anion scavenging capacity of human seminal plasma. 873 38

It appears that redox regulation is an important mechanism for the control of transcription factor activation. The role of oxidation-reduction is probably determined in part by the structure of the transcription factors. For example, the presence of cysteine residues within the DNA binding sites may sensitize a transcription factor to ROS. The ROS-mediated regulation of transcription factors is specific, some ROS are more efficient than other ROS in activating defined regulators. While the protective antioxidant responses induced by ROS in prokaryotes and eukaryotes are rather conserved (for example, SOD, HSP...), the regulators for these genes do not appear to be conserved. Further studies designed to fully characterize these regulators and understand the subtle mechanisms involved in redox gene regulation are ongoing, and should provide the theoretical basis for clinical approaches using antioxidant therapies in human diseases in which oxidative stress is implicated.
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PMID:Transcriptional regulators of oxidative stress-inducible genes in prokaryotes and eukaryotes. 885 78


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