Elevated production of radical oxygen species by polymorphonuclear neutrophils in cerebrospinal fluid infection

Background/Aims: Accelerated atherosclerosis in chronic kidney disease (CKD) is preceded by endothelial dysfunction (ED), which exhibits a proinflammatory and prothrombotic phenotype and enhanced oxidative stress. In this study, the effect of several compounds with anti-inflammatory and/or antioxidant properties on uremia-induced endothelial dysfunction has been evaluated in an in vitro model. Methods: Endothelial cells (ECs) were exposed to sera from uremic patients in the absence and presence of the flavonoids apigenin, genistein and quercetin, the antioxidant enzyme mimetics (AEM) ebselen (glutathione peroxidase mimetic), EUK-134 and EUK-118 (both superoxide dismutase mimetics), and the pharmacological drug N-acetylcysteine (NAC). We explored changes in the expression of adhesion receptors on the cell surface, by immunofluorescence, the production of radical oxygen species (ROS), by fluorescence detection, and the activation of signaling proteins related to inflammation, by both a phosphospecific antibody cell-based ELISA and immunoblotting techniques. Results: Uremic media induced a significantly increased expression of ICAM-1, overproduction of radical oxygen species (ROS) and activation of p38 mitogen activated protein kinase (p38MAPK) and Nuclear Factor kB (NFkB) in ECs. Quercetin, the AEM and NAC showed a significant inhibitory effect on both ICAM-1 expression and ROS generation (p<0.05). All the compounds reduced p38MAPK activation, but only the AEM, especially ebselen, and NAC, both potentiating the glutathione peroxidase pathway, also inhibited NFkB activation. These two compounds were capable of increasing endothelial glutathione levels, especially in response to uremia. Conclusion: Our results indicate that the potentiation of the antioxidant pathways can be an effective strategy to improve endothelial dysfunction in uremia and a potential target to reduce the cardiovascular risk in this population.

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Production of radical oxygen species in exhaled breath condensate of patients affected by chronic obstructive pulmonary disease

Free Radical Biology and Medicine ◽

10.1016/j.freeradbiomed.2012.08.480 ◽

2012 ◽

Vol 53 ◽

pp. S229

Author(s):

I. Antonioli ◽

A. Padovani ◽

S. Pinamonti ◽

M. Contoli ◽

A. Papi ◽

...

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Pulmonary Disease ◽

Exhaled Breath Condensate ◽

Chronic Obstructive ◽

Exhaled Breath ◽

Oxygen Species ◽

Radical Oxygen Species ◽

Obstructive Pulmonary Disease ◽

Breath Condensate

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Clinical Isolates ofMycobacterium tuberculosisDiffer in Their Ability to Induce Respiratory Burst and Apoptosis in Neutrophils as a Possible Mechanism of Immune Escape

Clinical and Developmental Immunology ◽

10.1155/2012/152546 ◽

2012 ◽

Vol 2012 ◽

pp. 1-11 ◽

Cited By ~ 18

Author(s):

María M. Romero ◽

Luciana Balboa ◽

Juan I. Basile ◽

Beatriz López ◽

Viviana Ritacco ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Reference Strain ◽

Immune Escape ◽

Multidrug Resistant ◽

Polymorphonuclear Neutrophils ◽

Ros Production ◽

Oxygen Species ◽

Phenotypic Differences ◽

Induced Apoptosis ◽

P38 Pathway

Tuberculosis pathogenesis was earlier thought to be mainly related to the host but now it appears to be clear that bacterial factors are also involved. Genetic variability ofMycobacterium tuberculosis(Mtb) could be slight but it may lead to sharp phenotypic differences. We have previously reported that nonopsonizedMtbH37Rv induce apoptosis of polymorphonuclear neutrophils (PMNs) by a mechanism that involves the p38 pathway. Here we evaluated the capability to induce PMN apoptosis of two prevalentMtblineages in Argentina, the Latin America and Mediterranean (LAM), and Haarlem, using the H37Rv as a reference strain. Results showed that LAM strains strongly induced apoptosis of PMN which correlated with the induction of reactive oxygen species (ROS) production and p38 activation. Interestingly, the highly prosperous multidrug-resistant M strain, belonging to the Haarlem lineage, lacked the ability to activate and to induce PMN apoptosis as a consequence of (1) a weak ROS production and (2) the contribution of antiapoptotic mechanisms mediated at least by ERK. Although with less skill, M is able to enter the PMN so that phenotypic differences could lead PMN to be a reservoir allowing some pathogens to prevail and persist over other strains in the community.

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Formation of Oxidatively Modified Lipids as the Basis for a Cellular Epilipidome

Frontiers in Endocrinology ◽

10.3389/fendo.2020.602771 ◽

2020 ◽

Vol 11 ◽

Author(s):

Corinne M. Spickett

Keyword(s):

Biological Effects ◽

Oxidative Modification ◽

Oxygen Species ◽

Radical Oxygen Species ◽

Chemical Mechanisms ◽

Control Gene Expression ◽

Lipid Species ◽

Regulatory Effects ◽

Oxidatively Modified ◽

The Stability

While often regarded as a subset of metabolomics, lipidomics can better be considered as a field in its own right. While the total number of lipid species in biology may not exceed the number of metabolites, they can be modified chemically and biochemically leading to an enormous diversity of derivatives, many of which retain the lipophilic properties of lipids and thus expand the lipidome greatly. Oxidative modification by radical oxygen species, either enzymatically or chemically, is one of the major mechanisms involved, although attack by non-radical oxidants also occurs. The modified lipids typically contain more oxygens in the form of hydroxyl, epoxide, carbonyl and carboxylic acid groups, and nitration, nitrosylation, halogenation or sulfation can also occur. This article provides a succinct overview of the types of species formed, the reactive compounds involved and the specific molecular sites that they react with, and the biochemical or chemical mechanisms involved. In many cases, these modifications reduce the stability of the lipid, and breakdown products are formed, which themselves have interesting properties such as the ability to react with other biomolecules. Publications on the biological effects of modified lipids are growing rapidly, supporting the concept that some of these biomolecules have potential signaling and regulatory effects. The question therefore arises whether modified lipids represent an “epilipidome”, analogous to the epigenetic modifications that can control gene expression.

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