Erratum of the article: Antioxidant and Anti-Inflammatory Strategies Based on the Potentiation of Glutathione Peroxidase Activity Prevent Endothelial Dysfunction in Chronic Kidney Disease

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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Plasma and Erythrocyte Glutathione Peroxidase Activity, Serum Selenium Concentration, and Plasma Total Antioxidant Capacity in Cats with IRIS Stages I-IV Chronic Kidney Disease

Journal of Veterinary Internal Medicine ◽

10.1111/jvim.12264 ◽

2013 ◽

Vol 28 (1) ◽

pp. 130-136 ◽

Cited By ~ 16

Author(s):

M. Krofič Žel ◽

N. Tozon ◽

A. Nemec Svete

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Glutathione Peroxidase ◽

Peroxidase Activity ◽

Total Antioxidant Capacity ◽

Selenium Concentration ◽

Serum Selenium ◽

Glutathione Peroxidase Activity ◽

Total Antioxidant ◽

Serum Selenium Concentration

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Abstract 357: Antioxidant and Anti-inflammatory Strategies Prevent Endothelial Dysfunction in Chronic Kidney Disease

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.36.suppl_1.357 ◽

2016 ◽

Vol 36 (suppl_1) ◽

Author(s):

Marta Palomo ◽

Susana Martin-Rodriguez ◽

Manel Vera ◽

Josep Maria Cruzado ◽

Jose Rivera ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Endothelial Dysfunction ◽

Kidney Disease ◽

Antioxidant Enzyme ◽

Inhibitory Effect ◽

Ros Generation ◽

Protective Effects ◽

Anti Inflammatory ◽

Enzyme Mimetics

Accelerated atherosclerosis in chronic kidney disease (CKD) is preceded by the development of endothelial dysfunction (ED), with development of a proinflammatory and prothrombotic phenotype and enhanced oxidative stress. The effect of anti-inflammatory and antioxidant strategies on the endothelium has been evaluated in an in vitro model of ED in uremia. Endothelial cells (ECs) were pretreated with the antioxidant enzyme mimetics ebselen, EUK-134 and EUK-118; the flavonoids apigenin, genistein and quercetin, with both antioxidant and anti-inflammatory potential; and two commercially available compounds: N-acetylcysteine (NAC) and defibrotide (DF). There is increasing evidence demonstrating that both NAC and DF exhibit both properties. ECs were exposed to medium containing serum from patients on dialysis (n=10) or from healthy donors (n=15). Changes in the expression of the adhesion receptor ICAM-1 and the production of intracellular reactive oxygen species (ROS) were assessed. Activation of inflammation-related proteins p38 MAPK and NFkappaB (NFκB) were also evaluated. Exposure of ECs to uremic media resulted in a significantly increased expression of ICAM-1, overproduction of ROS and activation of p38MAPK and NFκB compared to control ECs (p<0.05). Ebselen, EUK 134, and EUK118 inhibited ICAM-1 expression and ROS generation in the uremic condition (p<0.01). Regarding flavonoids, only quercetin showed a moderated but significant inhibitory effect on both parameters (p<0.05). NAC and DF exhibited a protective effect on ECs exposed to the uremic insult (p<0.05 for ICAM-1 expression and ROS generation). All the compounds reduced p38MAPK activation (p<0.05). The antioxidant-enzyme mimetics and NAC were able to inhibit the activation of NFκB induced by the uremic media (p<0.05). Endothelial dysfunction associated with CKD is considered to be the first step in the progression of atherosclerosis. Our results indicate that the antioxidant enzyme mimetics, NAC and DF exhibit not only antioxidant but also anti-inflammatory effects on the endothelium. Therefore, further research on the protective effects of these compounds may provide new strategies for the prevention of the cardiovascular complications in uremia.

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Low Selenium Status in the Elderly Influences Thyroid Hormones

Clinical Science ◽

10.1042/cs0890637 ◽

1995 ◽

Vol 89 (6) ◽

pp. 637-642 ◽

Cited By ~ 64

Author(s):

Oliviero Olivieri ◽

Domenico Girelli ◽

Margherita Azzini ◽

Anna Maria Stanzial ◽

Carla Russo ◽

...

Keyword(s):

Glutathione Peroxidase ◽

Thyroid Hormones ◽

Peroxidase Activity ◽

Controlled Trial ◽

The Elderly ◽

Serum Selenium ◽

Selenium Status ◽

Glutathione Peroxidase Activity ◽

Double Blind ◽

Double Blind Placebo

1. Iodothyronine 5′-deiodinase, which is mainly responsible for peripheral triiodothyronine (T3) production, has recently been demonstrated to be a selenium-containing enzyme. In the elderly, reduced peripheral conversion of thyroxine (T4) to T3 and overt hypothyroidism are frequently observed. 2. We measured serum selenium and erythrocyte glutathione peroxidase (as indices of selenium status), thyroid hormones and thyroid-stimulating hormone in 109 healthy euthyroid subjects (52 women, 57 men), carefully selected to exclude abnormally low thyroid hormone levels induced by acute or chronic diseases or calorie restriction. The subjects were subdivided into three age groups. To avoid conditions of undernutrition or malnutrition, dietary records were obtained for a sample of 24 subjects, randomly selected and representative of the whole population for age and sex. 3. In order to properly assess the influence of selenium status on iodothyronine 5′-deiodinase type I activity, a double-blind placebo-controlled trial was also carried out on 36 elderly subjects, resident at a privately owned nursing home. 4. In the free-living population, a progressive reduction of the T3/T4 ratio (due to increased T4 levels) and of selenium and erythrocyte glutathione peroxidase activity was observed with advancing age. A highly significant linear correlation between T4, T3/T4 and selenium was observed in the population as a whole (for T4, R = −0.312, P < 0.002; for T3/T4 ratio, R = 0.32, P < 0.01) and in older subjects (for T4, R = −0.40, P < 0.05; for T3/T4 ratio, R = 0.54, P < 0.002). 5. The main result of the double-blind placebo-controlled trial was a significant improvement of selenium indices and a decrease in the T4 level in selenium-treated subjects; serum selenium, erythrocyte glutathione peroxidase activity and thyroid hormones did not change in placebo-treated subjects. 6. We concluded that selenium status influences thyroid hormones in the elderly, mainly modulating T4 levels.

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Selenium levels and glutathione peroxidase activity in patients with ataxia-telangiectasia: association with oxidative stress and lipid status biomarkers

Orphanet Journal of Rare Diseases ◽

10.1186/s13023-021-01732-5 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Itana Gomes Alves Andrade ◽

Fabíola Isabel Suano-Souza ◽

Fernando Luiz Affonso Fonseca ◽

Carolina Sanchez Aranda Lago ◽

Roseli Oselka Saccardo Sarni

Keyword(s):

Oxidative Stress ◽

Glutathione Peroxidase ◽

Peroxidase Activity ◽

Oxidized Ldl ◽

Reference Value ◽

Glutathione Peroxidase Activity ◽

Oxidative Stress Biomarkers ◽

Apo B ◽

Lipid Status ◽

And Oxidative Stress

Abstract Introduction Ataxia-Telangiectasia (A-T) is a multi-system disorder that may be associated with endocrine changes, oxidative stress in addition to inflammation. Studies suggest that selenium is a trace element related to protection against damage caused by oxidative stress. Objective To describe the plasma levels of selenium and erythrocyte glutathione peroxidase activity in A-T patients and to relate them to oxidative stress and lipid status biomarkers. Methods This is a cross-sectional and controlled study evaluating 22 A-T patients (age median, 12.2 years old) matched by gender and age with 18 healthy controls. We evaluated: nutritional status, food intake, plasma selenium levels, erythrocyte glutathione peroxidase activity, lipid status, inflammation and oxidative stress biomarkers. Results Adequate levels of selenium were observed in 24/36 (66.7%) in this evaluated population. There was no statistically significant difference between the groups in selenium levels [47.6 μg/L (43.2–57.0) vs 54.6 (45.2–62.6) μg/dL, p = 0.242]. Nine of A-T patients (41%) had selenium levels below the reference value. The A-T group presented higher levels of LDL-c, non-HDL-c, oxidized LDL, Apo B, Apo-B/Apo-A-I1, LDL-c/HDL-c ratio, malondialdehyde [3.8 µg/L vs 2.8 µg/L, p = 0.029] and lower Apo-A-I1/HDL-c and glutathione peroxidase activity [7300 U/L vs 8686 U/L, p = 0.005]. Selenium levels were influenced, in both groups, independently, by the concentrations of oxidized LDL, malonaldehyde and non-HDL-c. The oxidized LDL (AUC = 0.849) and ALT (AUC = 0.854) were the variables that showed the greatest discriminatory power between groups. Conclusion In conclusion, we observed the presence of selenium below the reference value in nearly 40% and low GPx activity in A-T patients. There was a significant, inverse and independent association between selenium concentrations and oxidative stress biomarkers. Those data reinforce the importance of assessing the nutritional status of selenium in those patients.

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The distribution, induction and isoenzyme profile of glutathione S-transferase and glutathione peroxidase in isolated rat liver parenchymal, Kupffer and endothelial cells

Biochemical Journal ◽

10.1042/bj2640737 ◽

1989 ◽

Vol 264 (3) ◽

pp. 737-744 ◽

Cited By ~ 18

Author(s):

P Steinberg ◽

H Schramm ◽

L Schladt ◽

L W Robertson ◽

H Thomas ◽

...

Keyword(s):

Endothelial Cells ◽

Glutathione Peroxidase ◽

Rat Liver ◽

Peroxidase Activity ◽

Cell Types ◽

Transferase Activity ◽

Glutathione Peroxidase Activity ◽

Glutathione S Transferase ◽

Liver Parenchymal ◽

Parenchymal Cells

The distribution and inducibility of cytosolic glutathione S-transferase (EC 2.5.1.18) and glutathione peroxidase (EC 1.11.1.19) activities in rat liver parenchymal, Kupffer and endothelial cells were studied. In untreated rats glutathione S-transferase activity with 1-chloro-2,4-dinitrobenzene and 4-hydroxynon-2-trans-enal as substrates was 1.7-2.2-fold higher in parenchymal cells than in Kupffer and endothelial cells, whereas total, selenium-dependent and non-selenium-dependent glutathione peroxidase activities were similar in all three cell types. Glutathione S-transferase isoenzymes in parenchymal and non-parenchymal cells isolated from untreated rats were separated by chromatofocusing in an f.p.l.c. system: all glutathione S-transferase isoenzymes observed in the sinusoidal lining cells were also detected in the parenchymal cells, whereas Kupffer and endothelial cells lacked several glutathione S-transferase isoenzymes present in parenchymal cells. At 5 days after administration of Arocolor 1254 glutathione S-transferase activity was only enhanced in parenchymal cells; furthermore, selenium-dependent glutathione peroxidase activity decreased in parenchymal and non-parenchymal cells. At 13 days after a single injection of Aroclor 1254 a strong induction of glutathione S-transferase had taken place in all three cell types, whereas selenium-dependent glutathione peroxidase activity remained unchanged (endothelial cells) or was depressed (parenchymal and Kupffer cells). Hence these results clearly establish that glutathione S-transferase and glutathione peroxidase are differentially regulated in rat liver parenchymal as well as non-parenchymal cells. The presence of glutathione peroxidase and several glutathione S-transferase isoenzymes capable of detoxifying a variety of compounds in Kupffer and endothelial cells might be crucial to protect the liver from damage by potentially hepatotoxic substances.

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