Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
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.
 ...
PMID:DNA damage by smoke: protection by turmeric and other inhibitors of ROS. 193 45

Relationships among the plasma levels of vitamin E (VE), the numbers and prooxidative activities of circulating phagocytes, serum alpha-1-protease inhibitor (API), and pulmonary functions were investigated in 83 asymptomatic male cigarette smokers and 65 nonsmoking controls. Plasma levels of VE, of cholesterol, and of API were measured using high performance liquid chromatography, spectrophotometry, and nephelometry, respectively, whereas reactive oxidant (ROS) generation by activated blood phagocytes was measured using a whole blood luciginen-enhanced chemiluminescence method. Smoking was associated with significantly increased circulating neutrophil counts (p 0.0001), serum API (p 0.0001) and phagocyte-derived ROS-generation (p 0.0001), and decreased spirometric values (FEV1: p 0.0138 and FEF25-75: p 0.0654). Plasma VE and cholesterol levels were not significantly different between smokers and nonsmokers. However, in smokers both plasma VE and cholesterol correlated significantly and positively with serum API (r 0.24, p 0.03 and r 0.30, p 0.005, respectively), neutrophil counts (r 0.24, p 0.03 and r 0.25, p 0.03, respectively), and phagocyte-derived ROS-generation (r 0.32, p 0.003 and r 0.32, p 0.003, respectively), and significantly and inversely with FEV1 (r -0.23, p 0.03 and r -0.22, p 0.04, respectively) and FEF25-75 (r -0.32, p 0.003 and r -0.26, p 0.02, respectively). In nonsmokers plasma VE, but not cholesterol, was positively correlated with FEV1 (r 0.34, p 0.007) and FEF25-75 (r 0.40, p 0.001). The results suggest that VE protects the lungs of both smokers and nonsmokers and may act as a mobilizable antioxidant in response to smoking-induced oxidative stress.
 ...
PMID:Vitamin E, pulmonary functions, and phagocyte-mediated oxidative stress in smokers and nonsmokers. 779 4

Reactive oxygen-mediated processes are though to contribute to the pathogenesis of Alzheimer's disease (AD). To investigate this hypothesis we studied autopsy tissue from 11 pairs of AD cases and control individuals matched for age, postmortem delay, and tissue storage time. The temporal neocortex, which is severely involved by AD pathology, and the cerebellum, which is spared, were analyzed for tissue markers of lipid peroxidation (LPO). The average chemiluminescence formed from bond breakage in tissue homogenates during a 3-h incubation, without the presence of catalysts such as metal ions or ascorbate, was significantly increased in the AD temporal cortex to 130% of matched controls. Basal tissue content of LPO products (thiobarbituric acid reactive substances--TBARs) was not different between groups. However, TBARs were significantly elevated in AD temporal cortex to 135% of control after the incubation. In contrast, in the cerebellum there was no difference between AD and control tissue, indicating a disease-specific tissue effect. Because the use of oral antioxidants have received considerable attention in the last few years, the results seen in the testing of an AD patient who took daily vitamin E supplements for 4 years is particularly interesting. The time course for CL reactivity in the temporal cortex was considerably delayed compared to all other samples. This observation is consistent with the hypothesis that antioxidants within tissue will quench ROS-mediated reactions. This study indicates that there is increased susceptibility to ROS in the AD temporal cortex that may contribute to the pathogenesis of the disease. Furthermore, our observation suggest that oral antioxidant supplementation may be protective against LPO in the human brain.
 ...
PMID:Increased susceptibility of Alzheimer's disease temporal cortex to oxygen free radical-mediated processes. 919 80

Postnatally a rapid change occurs from a relatively hypoxic to a relatively hyperoxic environment, especially during artificial ventilation with all risks of ROS-formation. Among the non enzymatic antioxidative strategies the vitamins E, C, A and B2 are of major importance. Vitamin E is considered the most important radical scavenging vitamin of the lipid soluble compartment. Hereby vitamin E itself is converted into a radical which is handed over to vitamin C and glutathione into the water soluble compartment. The vitamin E content of the fetus increases with the fetal fat mass mainly during the last trimester of pregnancy. Placenta is only slightly permeable to lipid soluble vitamins. Vitamin E deficiency may rapidly develop typically at about 6-8 weeks of age. Vitamin E is able to prolong significantly the onset of retinopathic changes during oxygen therapy and may prevent intraventricular hemorrhage. Vitamin C is together with glutathione a major representative of the non enzymatic antioxidative system in the water soluble compartment. The best determinant of the vitamin C status is its concentration in leukocytes. Vitamin C reduces iron to the divalent state which supports the hydroxyl radical formation (Haber-Weiss reaction). This should be considered mainly in cases of intraventricular hemorrhage. Vitamin B2 acts mainly as cofactor of glutathione reductase which keeps glutathione in the reduced state. It can therefore be considered an indirect antioxidative vitamin. Vitamin B2 is destroyed by light. Phototherapy has been recognized as a cause of riboflavin deficiency. Vitamin A comprises all retinols with properties like trans-retinol. Retinol storage in the fetal liver increases during late pregnancy. In both, premature and mature newborns, the serum concentrations amount to only about 50% of those of their mothers. Vitamin A has a paramount importance for fetal lung development, because the individual surfactant proteins are selectively regulated by retinoic acid.
 ...
PMID:Antioxidative vitamins in prematurely and maturely born infants. 935 Apr 73

Cardiovascular diseases represent the first cause of mortality in chronic renal failure patients treated by hemodialysis. Alterations in lipid metabolism and oxidative stress are recognized as vascular risk factors. Their corrections could be of interest for atherosclerosis prevention. In order to evaluate interest of an therapeutic intervention, we have analyzed oxidative metabolism in hemodialysis patients by determining the production of oxygen reactive species (ROS), the level of defense mechanisms, and the balance between nitric oxide (NO) and ROS, responsible for anti- or proxidant effects of NO. During dialysis sessions performed with cellulosic membrane (Cuprophan) an increase in hydroperoxide production by platelets was noted (12 HETE) (5.62 +/- 0.94 pg); similarly, superoxide anion (O2(0)-) production by monocytes (fluorescence index: 115 +/- 24) and by polynuclear cells (fluorescence index: 115 +/- 24) was enhanced. On the other hand, anti-oxidant defenses were significantly reduced with a decrease in RBC SOC activity (0.92 +/- 0.06 U/mg Hg) and in RBC vitamin E (0.7 +/- 0.07 mg/l) concentration. We have demonstrated a profound alteration in the L-arginine/NO pathway consequently to an accumulation of NO synthases inhibitors or activators. The necessity to reduce the production of ROS during dialysis sessions justifies the use of more biocompatible membranes, such as modified cellulosic or synthetic membranes, decreasing leucocyte activation. In addition, NO synthetase inhibitors can be preferentially eliminated by convection. Finally, a supplementation with an exogenous anti-oxidant, such as oral vitamin E (500 mg/day for 6 months) normalizes RBC vitamin E levels and concomitantly allows a decrease in MDA concentrations In conclusion, oxidative metabolism alterations observed in hemodialysis are multifactorial: preventive measures include the use of a more biocompatible material, the reequilibrium of the NO/ROS balance, and supplementation with exogenous anti-oxidants.
 ...
PMID:[Oxidative stress and chronic renal insufficiency: what can be a prophylactic approach?]. 940 62

A role for the antioxidants vitamin E and idebenone in decreasing retinal cell injury, after metabolic inhibition induced by chemical ischemia and hypoglycemia, was investigated and compared with oxidative stress conditions. Preincubation of the antioxidants, vitamin E (20 microM) and idebenone (10 microM), effectively protected from retinal cell injury after oxidative stress or hypoglycemia, whereas the protection afforded after postincubation of both antioxidants was decreased. Delayed retinal cell damage, mediated by chemical ischemia, was attenuated at 10 or 12 h postischemia, only after exposure to the antioxidants during all the experimental procedure. An antagonist of the N-methyl-D-aspartate (NMDA) receptors, an inhibitor of nitric oxide synthase (NOS) or a blocker of L-type Ca2+ channels were ineffective in reducing cell injury induced by chemical ischemia, hypoglycemia or oxidative stress. Oxidative stress and hypoglycemia increased (about 1.2-fold) significantly the fluorescence of the probe DCFH2-DA, that is indicative of intracellular ROS formation. Free radical generation detected with the probe dihydrorhodamine 123 (DHR 123) was enhanced after oxidative stress, chemical ischemia or hypoglycemia (about 2-fold). Nevertheless, the antioxidants vitamin E or idebenone were ineffective against intracellular ROS generation. Cellular energy charge decreased greatly after chemical ischemia, was moderately affected after hypoglycemia, but no significant changes were observed after oxidative stress. Preincubation with vitamin E prevented the changes in energy charge upon 6 h posthypoglycemia. We can conclude that irreversible changes occurring during chemical ischemia mainly reflect the alterations taking place at the ischemic core, whereas hypoglycemia situations may reflect changes occurring at the penumbra area, whereby vitamin E or idebenone may help to increase cell survival, exerting a beneficial neuroprotective effect.
 ...
PMID:Influence of the antioxidants vitamin E and idebenone on retinal cell injury mediated by chemical ischemia, hypoglycemia, or oxidative stress. 1040 4

Lipid peroxidation in aliquots of bovine retina (without rod outer segments, ROS), purified ROS and retinal pigment epithelium (RPE) was initiated with 5 mM ferric iron and 80 mM ADP. After 30 min of oxidation at 37 degrees C, the concentration of thiobarbituric-acid-reacting substances (TBARS) which approximates lipid hydroperoxide (LHP), increased in the ROS from 2.0 +/- 3.6 to 90.2 +/- 34.5 nmol malondialdehyde (MDA)/mg protein and in the RPE from 0.54 +/- 0.2 to 51.5 +/- 15.8 nmol MDA/mg protein. Sixteen lipid and aqueous antioxidants (AOX) from natural or synthetic sources, including five flavonoids, were evaluated for their ability to inhibit the oxidative reaction. Palm-oil-derived vitamin E showed significant protection in retina, ROS and RPE (64, 68 and 74%), respectively. Of the flavonoids tested, good protection in the retina was found at 10(-5) M for epigallocatechin gallate (50%) and at 50 ng/ml for pycnogenol (61%) and catechin (52%). When catechin and palm oil vitamin E, catechin and coenzyme Q(10) or coenzyme Q(10) and pycnogenol were combined, the individual effect was enhanced. TBARS as an indirect measure of LHP level and hemoglobin-methylene blue determination for direct LHP were used as alternative end-point determinations of lipid peroxidation. These measure different aspects of AOX reactions. The results demonstrate the usefulness of an in vitro model system that can rapidly and accurately determine the capacity of a single AOX against lipid peroxidation or be used to show synergistic efficacy.
 ...
PMID:In vitro testing of antioxidants and biochemical end-points in bovine retinal tissue. 1047 69

Free radicals derived from the reaction of iron and oxygen are thought to be one of the causes of tissue injury. In order to identify whether oxygen concentrations are an important factor in iron-mediated damage to cells, cytotoxic effects of Fe(3+)-NTA on human fibroblasts (KMST-6 line) were studied under the conditions of 1% and 20% oxygen concentrations in an incubator. A comparison of the effects of Fe(3+)-NTA on cells cultured in 1% and 20% oxygen environments showed that the following features were more prominent under the usual culture concentrations of 20% oxygen: i) cytotoxicity, ii) increase in intracellular reactive oxygen species, iii) increase in H(2)O(2) production in the cells, and iv) formation of 8-hydroxydeoxyguanosine. To elucidate the roles of endogenous antioxidants, the levels of manganese superoxide dismutase (MnSOD) and catalase were measured by Western blotting. The increase in MnSOD in the presence of Fe(3+)-NTA was greater under the condition of 20% O(2) than under the condition of 1% O(2). The expression of catalase was significantly up-regulated at 20% O(2). However, when the cells were treated with Fe(3+)-NTA, the expression of catalase was markedly down-regulated under the condition of 20% O(2). Hydroxyl radical scavengers such as vitamin E, dimethyl-sulfoxide (DMSO) and mannitol reduced endogenous ROS generation and alleviated the cytotoxic effects of iron. On the other hand, superoxide dismutase (SOD), vitamin C and catalase did not show any protective effects against Fe(3+)-NTA. These findings suggest that enhanced cytotoxic effects of Fe(3+)-NTA at 20% O(2 )are due to endogenously produced hydroxyl radicals.
 ...
PMID:Effects of oxygen concentrations on human fibroblasts treated with Fe(3+)-NTA. 1117 10

One-day-old chicks were reared using diets differing in their vitamin E and/or selenium content. The purpose of this research was to detect any possible imbalance in the antioxidant defense system, which could be related to development of nutritional pancreatic atrophy. Mitochondrial membranes from animals deficient in both nutrients, or just vitamin E, submitted to peroxidizability 'in vitro' had the production of TBARS greatly enhanced. Measurements of the 2-GSH/GSSG ratio suggested that selenium and vitamin E, the latter in higher magnitude, were responsible for maintenance of the reducing capacity of the cell. Enzymatic defense systems against oxidative stress were also studied. The results indicated that the total antioxidant enzymatic activity of pancreatic cells was not sufficient to scavenge all the ROS generated in the nutritionally deficient animals. The present study suggests that nutritional deficiency of selenium and/or vitamin E generates one imbalance between pro-oxidant and antioxidant systems in chicken pancreas, leading to oxidative stress and pancreatic atrophy.
 ...
PMID:Role of antioxidant systems in induced nutritional pancreatic atrophy in chicken. 1192 94

Liver damage ranges from acute hepatitis to hepatocellular carcinoma, through apoptosis, necrosis, inflammation, immune response, fibrosis, ischemia, altered gene expression and regeneration, all processes that involve hepatocyte, Kupffer, stellate, and endothelial cells. Reactive oxygen and nitrogen species (ROS, RNS) play a crucial role in the induction and in the progression of liver disease, independently from its etiology. They are involved in the transcription and activation of a large series of cytokines and growth factors that, in turn, can contribute to further production of ROS and RNS. The main sources of free radicals are represented by hepatocyte mitochondria and cytochrome p450 enzymes, by endotoxin-activated macrophages (Kupffer cells), and by neutrophils. The consequent alteration of cellular redox state is potentiated by the correlated decrease of antioxidant and energetic reserves. Indices of free radical-mediated damage, such as the increase of malondialdehyde, 4-hydroxynonenal, protein-adducts, peroxynitrite, nitrotyrosine, etc., and/or decrease of glutathione, vitamin E, vitamin C, selenium, etc., have been documented in patients with viral or alcoholic liver disease. These markers may contribute to the monitoring the degree of liver damage, the response to antiviral therapies and to the design of new therapeutic strategies. In fact, increasing attention is now paid to a possible "redox gene therapy." By enhancing the antioxidant ability of hepatocytes, through transgene vectors, one could counteract oxidative/nitrosative stress and, in this way, contribute to blocking the progression of liver disease.
 ...
PMID:Oxidative stress in viral and alcoholic hepatitis. 1249 74


1 2 3 4 5 6 7 8 9 10 Next >>