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Nitrosative Stress (nitrosative + stress)

Distribution by Scientific Domains

Life Sciences	68%
Medical Sciences	26%

Selected Abstracts

Nitrosative stress induced cytotoxicity in Giardia intestinalis

JOURNAL OF APPLIED MICROBIOLOGY, Issue 3 2003
D. Lloyd
Abstract Aims: To investigate the antigiardial properties of the nitrosating agents: sodium nitrite, sodium nitroprusside and Roussin's black salt. Methods and Results: Use of confocal laser scanning microscopy and flow cytometry indicated permeabilization of the plasma membrane to the anionic fluorophore, DiBAC4(3) [bis(1,3-dibutylbarbituric acid) trimethine oxonol]. Loss of plasma membrane electrochemical potential was accompanied by loss of regulated cellular volume control. Changes in ultrastructure revealed by electron microscopy and capacity for oxygen consumption, were also consequences of nitrosative stress. Roussin's black salt (RBS), active at micromolar concentrations was the most potent of the three agents tested. Conclusions: These multitargeted cytotoxic agents affected plasma membrane functions, inhibited cellular functions in Giardia intestinalis and led to loss of viability. Significance and Impact of the Study: Nitrosative damage, as an antigiardial strategy, may have implications for development of chemotherapy along with suggesting natural host defence mechanisms. [source]

Nitric oxide and p53 in cancer-prone chronic inflammation and oxyradical overload disease,

ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 1 2004
Julie E. Goodman
Abstract Nitric oxide (NO·), which is generated under chronic inflammatory conditions that predispose individuals to cancer, has paradoxical effects. NO· can activate p53, which can result in anti-carcinogenic effects, or it can be mutagenic and increase cancer risk. We explored the mechanisms by which NO· induced p53 activation in vitro and found that NO· induced p53 accumulation and phosphorylation, particularly at ser-15, via ATM and ATR kinases, which then led to cell cycle arrest at G2/M. We next examined proteins in these pathways in both inflamed and normal human colon tissue. Inducible nitric oxide synthase (iNOS) levels and p53-P-ser15 levels were positively correlated with the degree of inflammation and with each other. Additionally, the p53 targets, HDM-2 and p21 (WAF1), were present in ulcerative colitis (UC) colon, but undetectable in normal colon, consistent with activated p53. We also found higher p53 mutant frequencies of both G:C , A:T transitions at the CpG site of codon 248 and C:G , T:A transitions at codon 247 in lesional colon tissue from UC cases versus nonlesional tissue from these cases or colon tissue from normal adult controls. Consistent with nitrosative stress and the deamination of 5-methylcytosine, p53 mutations were also detected in sporadic colon cancer tissue and were associated with iNOS activity in these tissues. These studies identified a potential mechanistic link between NO· and p53 in UC and sporadic colon cancer. Environ. Mol. Mutagen. 44:3,9, 2004. Published 2004 Wiley-Liss, Inc. [source]

The pentose-phosphate pathway in neuronal survival against nitrosative stress

IUBMB LIFE, Issue 1 2010
Juan P. Bolaños
Abstract Neurons are thought to be particularly vulnerable cells against reactive oxygen and nitrogen species (RONS) damage (nitrosative stress), due in part to their weak antioxidant defense and low ability to compensate energy homeostasis. Intriguingly, nitrosative stress efficiently stimulates the rate of the antioxidant pentose-phosphate pathway (PPP), which generates NADPH a necessary cofactor for the reduction of glutathione disulfide. In fact, inhibition of PPP sensitizes cultured neurons to glutathione oxidation and apoptotic death, whereas its stimulation confers resistance to nitrosative stress. Furthermore, we recently described that neurons can preferentially use glucose through the PPP by inhibiting glycolysis, which is achieved by continuously degrading the glycolytic positive-effector protein, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 (Pfkfb3) by the action of the E3 ubiquitine ligase anaphase-promoting complex/cyclosome (APC/C)Cdh1. These results suggest that the antioxidant fragility of neurons may be compensated by the PPP at the expense of inhibiting bioenergetic glycolysis. © 2009 IUBMB IUBMB Life, 62(1):14,18, 2010 [source]

Nitrosative stress induced cytotoxicity in Giardia intestinalis

Contribution of glutamatergic signaling to nitrosative stress-induced protein misfolding in normal brain aging and neurodegenerative diseases

AGING CELL, Issue 3 2007
Tomohiro Nakamura
Summary Glutamatergic hyperactivity, associated with Ca2+ influx and consequent production of nitric oxide (NO), is potentially involved in both normal brain aging and age-related neurodegenerative disorders. Many neurodegenerative diseases are characterized by conformational changes in proteins that result in their misfolding and aggregation. Normal protein degradation by the ubiquitin-proteasome system can prevent accumulation of aberrantly folded proteins. Our recent studies have linked nitrosative stress to protein misfolding and neuronal cell death. In particular, molecular chaperones , such as protein disulfide isomerase, glucose regulated protein 78, and heat shock proteins , can provide neuroprotection from misfolded proteins by facilitating proper folding and thus preventing aggregation. Here, we present evidence for the hypothesis that NO contributes to normal brain aging and degenerative conditions by S-nitrosylating specific chaperones that would otherwise prevent accumulation of misfolded proteins. [source]

Colorectal carcinoma development in inducible nitric oxide synthase-deficient mice with dextran sulfate sodium-induced ulcerative colitis

MOLECULAR CARCINOGENESIS, Issue 5 2007
Darren N. Seril
Abstract The overproduction of reactive oxygen and nitrogen species (RONS) may play an important role in ulcerative colitis (UC)-associated carcinogenesis. In order to study the role of nitric oxide (NO) in UC-associated colorectal carcinogenesis, the development of colorectal carcinoma was studied using the DSS-induced and iron-enhanced model of chronic UC in inducible nitric oxide synthase (iNOS)-deficient mice. Female wild-type C57BL/6 (iNOS+/+) and iNOS,/, mice were administered 1% DSS (w/v) through the drinking fluid for 15 DSS cycles and fed twofold iron-enriched diet. Colorectal inflammation and mucosal ulceration of moderate severity were observed in both iNOS+/+ and iNOS,/, mice. Similar tumor incidence and multiplicity in the colon were observed that 15 out of 23 (65.2%) iNOS+/+ mice developed colorectal tumors with a tumor multiplicity of 1.47,±,0.17 (mean,±,SE) after 15 DSS cycles, and 13 out of 19 (68.4%) iNOS,/, mice developed colorectal tumors with a tumor multiplicity of 2.08,±,0.21. Histopathologically, the tumors were confirmed to be well-differentiated adenocarcinomas. Nitrotyrosine, an indicator of peroxynitrite-caused protein modification, was detectable by immunohistochemistry in inflammatory cells and epithelial cells of the colon in iNOS+/+ and iNOS,/, mice, and no difference in staining intensity was observed between the two groups. Immunostaining for endothelial NOS (eNOS) was observed in lamina propria macrophages and colonic blood vessels, and eNOS protein levels were increased in the inflamed colon. These results show that there is no difference in UC-associated cancer development in iNOS+/+ and iNOS,/, mice, and suggest that in the absence of iNOS, other factors, such as eNOS, may play a role in nitrosative stress and UC-associated carcinogenesis in this model system. © 2006 Wiley-Liss, Inc. [source]

New functions for the ancient globin family: bacterial responses to nitric oxide and nitrosative stress

MOLECULAR MICROBIOLOGY, Issue 4 2000
MicroReview
Globin-like oxygen-binding proteins occur in bacteria, yeasts and other fungi, and protozoa. The simplest contain protohaem as sole prosthetic group, but show considerable variation in their similarity to the classical animal globins and plant globins. Flavohaemoglobins comprise a haem domain homologous to classical globins and a ferredoxin-NADP+ reductase (FNR)-like domain that converts the globin into an NAD(P)H-oxidizing protein with diverse reductase activities. In Escherichia coli, the prototype flavohaemoglobin (Hmp) is clearly involved in responses to nitric oxide (NO) and nitrosative stress: (i) the structural gene hmp is upregulated by NO and nitrosating agents; (ii) purified Hmp binds NO avidly, but also converts it to nitrate (aerobically) or nitrous oxide (anaerobically); (iii) hmp mutants are hypersensitive to NO and nitrosative stresses. Here, we review recent advances in E. coli and the growing number of microbes in which globins are known, draw particular attention to the essential chemistry of NO and related reactive species and their interactions with globins, and suggest that microbial globins have additional functions unrelated to ,NO' stresses. [source]

Early Renal Ischemia-Reperfusion Injury in Humans Is Dominated by IL-6 Release from the Allograft

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 7 2009
D. K. De Vries
The pathophysiology of ischemia/reperfusion (I/R) injury is complex, and current knowledge of I/R injury in humans is incomplete. In the present study, human living-donor kidney transplantation was used as a highly reproducible model to systematically study various processes potentially involved in early I/R injury. Unique, direct measurements of arteriovenous concentration differences over the kidney revealed massive release of interleukin (IL)-6 in the first 30 minutes of graft reperfusion and a modest release of IL-8. Among the assessed markers of oxidative and nitrosative stress, only 15(S)-8- iso -PGF2, was released. When assessing cell activation, release of prothrombin factor 1 + 2 indicated thrombocyte activation, whereas there was no release of markers for endothelial activation or neutrophil activation. Common complement activation complex sC5b-9 was not released into the bloodstream, but was released into urine rapidly after reperfusion. To investigate whether IL-6 plays a modulating role in I/R injury, a mouse experiment of renal I/R injury was performed. Neutralizing anti-IL-6 antibody treatment considerably worsened kidney function. In conclusion, this study shows that renal I/R in humans is dominated by local IL-6 release. Neutralization of IL-6 in mice resulted in a significant aggravation of renal I/R injury. [source]

Markers of oxidative and nitrosative stress in systemic lupus erythematosus: Correlation with disease activity,

ARTHRITIS & RHEUMATISM, Issue 7 2010
Gangduo Wang
Objective Free radical,mediated reactions have been implicated as contributors in a number of autoimmune diseases, including systemic lupus erythematosus (SLE). However, the potential for oxidative/nitrosative stress to elicit an autoimmune response or to contribute to disease pathogenesis, and thus be useful when determining a prognosis, remains largely unexplored in humans. This study was undertaken to investigate the status and contribution of oxidative/nitrosative stress in patients with SLE. Methods Sera from 72 SLE patients with varying levels of disease activity according to the SLE Disease Activity Index (SLEDAI) and 36 age- and sex-matched healthy controls were evaluated for serum levels of oxidative/nitrosative stress markers, including antibodies to malondialdehyde (anti-MDA) protein adducts and to 4-hydroxynonenal (anti-HNE) protein adducts, MDA/HNE protein adducts, superoxide dismutase (SOD), nitrotyrosine (NT), and inducible nitric oxide synthase (iNOS). Results Serum analysis showed significantly higher levels of both anti,MDA/anti,HNE protein adduct antibodies and MDA/HNE protein adducts in SLE patients compared with healthy controls. Interestingly, not only was there an increased number of subjects positive for anti-MDA or anti-HNE antibodies, but also the levels of both of these antibodies were statistically significantly higher among SLE patients whose SLEDAI scores were ,6 as compared with SLE patients with lower SLEDAI scores (SLEDAI score <6). In addition, a significant correlation was observed between the levels of anti-MDA or anti-HNE antibodies and the SLEDAI score (r = 0.734 and r = 0.647, respectively), suggesting a possible causal relationship between these antibodies and SLE. Furthermore, sera from SLE patients had lower levels of SOD and higher levels of iNOS and NT compared with healthy control sera. Conclusion These findings support an association between oxidative/nitrosative stress and SLE. The stronger response observed in serum samples from patients with higher SLEDAI scores suggests that markers of oxidative/nitrosative stress may be useful in evaluating the progression of SLE and in elucidating the mechanisms of disease pathogenesis. [source]

In Vitro Protective Effect of Hypericum androsaemum Extract Against Oxygen and Nitrogen Reactive Species

BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 4 2009
Isabel F. Almeida
Oxidative stress and nitrosative stress are common pathogenetic mechanisms contributing to initiation and progression of hepatic damage in several liver disorders. In the present study, an ethanol:water (4:6) extract from H. androsaemum branches and leaves were evaluated for its putative in vitro scavenging effects on 1,1-diphenyl-2-picrylhydrazil radical, on reactive oxygen species, namely HO,, O2,,, ROO,, 1O2 and H2O2 and on reactive nitrogen species, namely ,NO and ONOO,. The hypericum extract presented a remarkable capacity to scavenge all the tested reactive species, all the IC50 values being found at the ,g/ml level. IC50 values for 1,1-diphenyl-2-picrylhydrazil, and for the reactive oxygen species O2,,, H2O2, HO, and 1O2 were 11.3 ± 0.7, 32.7 ± 3.4, 944 ± 47, 595 ± 82, 28.3 ± 1.2 ,g/ml respectively. The oxygen radical absorbance capacity value obtained for ROO, was 1.5 ± 0.1 ,mol Trolox equivalents/mg extract. The IC50 values for ,NO and ONOO, were 2.2 ± 0.2 and 1.2 ± 0.1 ,g/ml respectively. The content of total phenolics was 281 ± 2 mg of gallic acid equivalents/g of lyophilized extract. The observed antioxidant activity provides scientific support for the reported therapeutic use of H. androsaemum, though further in vitro and in vivo studies are required to ascertain the risk/benefit score at therapeutic concentrations. [source]

Protective Effect of Ebselen, a Selenoorganic Drug, against Gentamicin-Induced Renal Damage in Rats

BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 3 2006
R. Dhanarajan
However, its clinical use is limited by its nephrotoxicity. Oxidative stress and nitrosative stress are reported to play important role in gentamicin nephrotoxicity. In the present study we investigated whether ebselen, an inhibitor of oxidative stress and nitrosative stress prevents or reduces gentamicin-induced renal damage in the rat. For this purpose male Wistar rats were divided into five groups and treated as follows. Group 1 (control group): dimethyl sulphoxide, intraperitoneally, Group 2: Gentamicin 100 mg/kg b.wt. subcutaneously, Group 3: 5 mg/g b.wt. ebselen intraperitoneally, Group 4: 2.5 mg/kg b.wt. ebselen followed by 100 mg/kg b.wt. gentamicin subcutaneously one hour later, and Group 5: 5 mg/kg b.wt. of ebselen followed by 100 mg/kg b.wt. gentamicin one hour later for four consecutive days. Nephrotoxicity was evaluated histopathologically by light microscopy, and biochemically by the measurement of the plasma creatinine and urea levels. Parameters of oxidative stress such as reduced glutathione, malondialdehyde, and activities of superoxide dismutase and glutathione peroxidase were measured in the kidney. Serum nitrite and nitrate were measured as indicators of nitrosative stress. Treatment of rats with gentamicin resulted in statistically significant reduction in reduced glutathione levels (51%) and the activities of antioxidant enzymes superoxide dismutase (56%) and glutathione peroxidase (39%) as compared with the controls in the kidneys. Renal malondialdehyde level was increased significantly (43%) as compared with the controls. Plasma creatinine levels, urea levels and nitrite levels were significantly increased (4, 4.5 and 160% times respectively) as compared with the controls. Histologically, damage to the renal cortex and medulla was observed moderate to severe tubular necrosis and glomerular congestion. Pretreatment with 2.5 mg/kg b.wt. ebselen prevented gentamicin induced damage to medulla; however, renal cortex showed mild damage and biochemically indicators of oxidative stress and nitrosative stress were significantly reduced. Pretreatment with 5 mg/kg b.wt. ebselen prevented gentamicin-induced oxidative damage and nitrosative damage and renal damage almost completely in 78% of the rats, in the other 22% of the rats, ebselen pretreatment reduced gentamicin-induced renal damage. The results of the present study suggest that ebselen may be useful as a nephroprotective agent. [source]

Effects of antioxidant stobadine on protein carbonylation, advanced oxidation protein products and reductive capacity of liver in streptozotocin-diabetic rats: Role of oxidative/nitrosative stress

BIOFACTORS, Issue 3 2007
Ahmet Cumao
Background: Increased oxidative/nitrosative stress is important in the pathogenesis of diabetic complications, and the protective effects of antioxidants are a topic of intense research. The purpose of this study was to investigate whether a pyridoindole antioxidant stobadine (STB) have a protective effect on tissue oxidative protein damage represented by the parameters such as protein carbonylation (PC), protein thiol (P-SH), total thiol (T-SH) and non-protein thiol (Np-SH), nitrotyrosine (3-NT), and advanced oxidation protein products (AOPP) in streptozotocin-diabetic rats. Methods: Diabetes was induced in male Wistar rats by intraperitonal injection of streptozotocin (55 mg/kg). Some of the non-diabetic (control) and diabetic rats treated with STB (24.7 mg/kg/day) during 16 weeks, and the effects on blood glucose, PC, AOPP, 3-NT, P-SH, T-SH and Np-SH were studied. Biomarkers were assayed by enzyme-linked immunosorbent assay (ELISA) or by colorimetric methods. Results: Administration of stobadine to diabetic animals lowered elevated blood glucose levels by ,16% relative to untreated diabetic rats. Although stobadine decreased blood glucose, poor glycemic control was maintained in stobadine treated diabetic rats during the treatment period. Biochemical analyses of liver proteins showed significant diminution of sulfhydryl groups, P-SH, T-SH, Np-SH, and elevation of carbonyl groups in diabetic animals in comparison to healthy controls. As a biomarker of nitrosative stress, 3-NT levels did not significantly change by diabetes induction or by stobadine treatment when compared to control animals. However, the treatment with stobadine resulted in a significant decrease in PC, AOPP levels and normalized P-SH, T-SH, Np-SH groups in liver of diabetic animals. [source]

6-Gingerol prevents cisplatin-induced acute renal failure in rats

BIOFACTORS, Issue 3 2006
Anurag Kuhad
Abstract Background: Nephrotoxicity is a major complication and a dose limiting factor for cisplatin therapy. Recent evidence suggests that enhanced oxidative stress caused by oxygen-centered free radicals may contribute to the pathogenesis of cisplatin-induced acute renal failure. 6-Gingerol is claimed to be a potent antioxidant. The present study was performed to explore the renoprotective potential of 6-gingerol on cisplatin-induced oxidative stress and renal dysfunction. Methods: 6-Gingerol in dosages of 12.5, 25, 50 mg/kg was administered 2 days before and 3 days after cisplatin administration. Renal injury was assessed by measuring serum creatinine, blood urea nitrogen, creatinine, urea clearance and serum nitrite levels. Renal oxidative stress was assessed by determining renal malondialdehyde levels, reduced glutathione levels and enzymatic activities of superoxide dismutase and catalase. Results: A single dose of cisplatin resulted in marked renal oxidative and nitrosative stress and significantly deranged renal functions. 6-Gingerol treatment significantly and dose-dependently restored renal functions, reduced lipid peroxidation and enhanced the levels of reduced glutathione and activities of superoxide dismutase and catalase. Conclusions: The present study demonstrates the renoprotective potential of 6-gingerol against cisplatin-induced oxidative stress and renal dysfunction in rats. Hence, 6-gingerol has a potential to be used as therapeutic adjuvant in cisplatin nephrotoxicity. [source]

Can coenzyme Q10 improve vascular function and blood pressure?

BIOFACTORS, Issue 1-4 2003
Potential for effective therapeutic reduction in vascular oxidative stress
Abstract Coenzyme Q10 (CoQ) is an endogenously synthesised compound that acts as an electron carrier in the mitochondrial electron transport chain. The presence of adequate tissue concentrations of CoQ may be important in limiting oxidative and nitrosative damage in vivo. Oxidative and nitrosative stress are likely to be elevated in conditions such as diabetes and hypertension. In these conditions elevated oxidative and nitrosative stress within the arterial wall may contribute to increased blood pressure and vascular dysfunction. The major focus of this review is the potential of CoQ to improve vascular function and lower blood pressure. Although there is substantial indirect support for the putative mechanism of effect of CoQ on the vascular system, to date there is little direct support for an effect of CoQ on in vivo markers of oxidative or nitrosative stress. The limited data available from studies in animal models and from human intervention studies are generally consistent with a benefit of CoQ on vascular function and blood pressure. The observed effects of CoQ on these endpoints are potentially important therapeutically. However, before any firm clinical recommendations can be made about CoQ supplementation, further intervention studies in humans are needed to investigate the effects of CoQ on vascular function, blood pressure and cardiovascular outcomes. The particularly relevant groups of patients for these studies are those with insulin resistance, type 2 diabetes, hypertension and the metabolic syndrome. [source]

Role of ,-glutamyltransferase in the homeostasis of glutathione during oxidative and nitrosative stress,

BIOFACTORS, Issue 1-4 2003
N.-E. Huseby
First page of article [source]

Preliminary X-ray crystallographic analysis of a nitric oxide-inducible lactate dehydrogenase from Staphylococcus aureus

ACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 10 2009
Jia-Bin Dong
Recent studies have indicated that Staphylococcus aureus can survive the nitrosative stress (caused by the radical nitric oxide; NO·) mounted by the immune system of the infected host. It does this by expressing a nitric oxide-inducible l -lactate dehydrogenase (Sa-LDH-1). Therefore, if efficient inhibitors of Sa-LDH-1 can be designed then Sa-LDH-1 could be a potential drug target against the pathogen S. aureus. For this purpose, the nitric acid-inducible LDH-1 from S. aureus COL strain has been cloned into the expression vector pET-28a(+) and the protein has been expressed, purified and crystallized. The Sa-LDH-1 crystal diffracted to 2.4,Å resolution at a home X-ray source and belonged to space group C2, with unit-cell parameters a = 131.4, b = 74.4, c = 103.2,Å, , = 133.4°. [source]