pH-dependent transformation products and residual toxicity evaluation of sulfamethoxazole degradation through non-radical oxygen species involved process

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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Trypanosoma cruzi: death phenotypes induced by ortho-naphthoquinone substrates of the aldo-keto reductase (TcAKR). Role of this enzyme in the mechanism of action of β-lapachone

Parasitology ◽

10.1017/s0031182018000045 ◽

2018 ◽

Vol 145 (9) ◽

pp. 1251-1259 ◽

Cited By ~ 1

Author(s):

Patricia Andrea Garavaglia ◽

María Fernanda Rubio ◽

Marc Laverrière ◽

Laura Mónica Tasso ◽

Laura Edith Fichera ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Trypanosoma Cruzi ◽

Mitochondrial Membrane ◽

Major Influence ◽

Ros Production ◽

Oxygen Species ◽

Aetiological Agent ◽

Toxicity Evaluation

AbstractSeveral ortho-naphthoquinones (o-NQs) have trypanocidal activity against Trypanosoma cruzi, the aetiological agent of Chagas disease. Previously, we demonstrated that the aldo-keto reductase from this parasite (TcAKR) reduces o-NQs, such as β-lapachone (β-Lap) and 9,10-phenanthrenequinone (9,10-PQ), with concomitant reactive oxygen species (ROS) production. Recent characterization of TcAKR activity and expression in two T. cruzi strains, CL Brener and Nicaragua, showed that TcAKR expression is 2.2-fold higher in CL Brener than in Nicaragua. Here, we studied the trypanocidal effect and induction of several death phenotypes by β-Lap and 9,10-PQ in epimastigotes of these two strains. The CL Brener strain was more resistant to both o-NQs than Nicaragua, indicating that greater TcAKR activity is unlikely to be a major influence on o-NQ toxicity. Evaluation of changes in ROS production, mitochondrial membrane potential, phosphatidylserine exposure and monodansylcadaverine labelling evidenced that β-Lap and 9,10-PQ induce different death phenotypes depending on the combination of drug and T. cruzi strain analysed. To study whether TcAKR participates in o-NQ activation in intact parasites, β-Lap and 9,10-PQ trypanocidal effect was next evaluated in TcAKR-overexpressing parasites. Only β-Lap was more effective and induced greater ROS production in TcAKR-overexpressing epimastigotes than in controls, suggesting that TcAKR may participate in β-Lap activation.

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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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