scholarly journals Effect of 5-Azacitidine Treatment on Redox Status and Inflammatory Condition in MDS Patients

Antioxidants ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 139
Author(s):  
Paola Montes ◽  
Ana Guerra-Librero ◽  
Paloma García ◽  
María Elena Cornejo-Calvo ◽  
María del Señor López ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Plasma Levels ◽  
Antioxidant Defense System ◽  
Redox Status ◽  
Markers Of Inflammation ◽  
Genetic Features ◽  
Advanced Stages ◽  
Endogenous Antioxidant ◽  
Plasma Nitrite ◽  
The Impact

This study focused on the impact of the treatment with the hypomethylating agent 5-azacitidine on the redox status and inflammation in 24 MDS patients. Clinical and genetic features of MDS patients were recorded, and peripheral blood samples were used to determine the activity of the endogenous antioxidant defense system (superoxide dismutase, SOD; catalase, CAT; glutathion peroxidase, GPx; and reductase, GRd, activities), markers of oxidative damage (lipid peroxidation, LPO, and advanced oxidation protein products, AOPP). Moreover, pro-inflammatory cytokines and plasma nitrite plus nitrate levels as markers of inflammation, as well as CoQ10 plasma levels, were also measured. Globally, MDS patients showed less redox status in terms of a reduction in the GSSG/GSH ratio and in the LPO levels, as well as increased CAT activity compared with healthy subjects, with no changes in SOD, GPx, and GRd activities, or AOPP levels. When analyzing the evolution from early to advanced stages of the disease, we found that the GPx activity, GSSG/GSH ratio, LPO, and AOPP increased, with a reduction in CAT. GPx changes were related to the presence of risk factors such as high-risk IPSS-R or mutational score. Moreover, there was an increase in IL-2, IL-6, IL-8, and TNF-α plasma levels, with a further increase of IL-2 and IL-10 from early to advanced stages of the disease. However, we did not observe any association between inflammation and oxidative stress. Finally, 5-azacitidine treatment generated oxidative stress in MDS patients, without affecting inflammation levels, suggesting that oxidative status and inflammation are two independent processes.

scholarly journals Effect of 5-Azacitine Treatment on Redox Status and Inflammatory Condition in MDS Patients

2021 ◽  
Author(s):  
Paola Montes ◽  
Ana Guerra-Librero ◽  
Paloma García ◽  
Mª Elena Cornejo-Calvo ◽  
Mª del Señor López ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Plasma Levels ◽  
Antioxidant Defense System ◽  
Redox Status ◽  
Markers Of Inflammation ◽  
Genetic Features ◽  
Advanced Stages ◽  
Endogenous Antioxidant ◽  
Plasma Nitrite ◽  
The Impact

This study focused on the impact of the treatment with the hypomethylating agent 5-Azacitidine on the redox status and inflammation in 24 MDS patients. Clinical and genetic features of MDS patients were recorded and peripheral blood samples were used to determine the activity of the endogenous antioxidant defense system (superoxide dismutase, SOD, catalase, CAT, glutathion peroxidase, GPx, and reductase, GRd, activities), markers of oxidative damage (lipid peroxidation, LPO, and advanced oxidation protein products, AOPP). Moreover, pro-inflammatory cytokines and plasma nitrite plus nitrate levels as markers of inflammation, and CoQ10 plasma levels, were also measured. Globally, MDS patients showed less redox status in terms of a reduction in the GSSG/GSH ratio and in the LPO levels, and increased CAT activity compared with healthy subjects, with not changes in SOD, GPx and GRd activities, and AOPP levels. When analyzed the evolution from early- to advanced stages of the disease, the GPx activity, GSSG/GSH ratio, LPO and AOPP increased, with a reduction in CAT. GPx changes were related with the presence of risk factors such as high-risk IPSS-R or mutational score. Besides, there was an increase in IL-2, IL-6, IL-8 and TNF-α plasma levels, with further increase of IL-2 and IL-10 from early to advanced stage of the disease. However, we did not observe any association between inflammation and oxidative stress. Finally, 5-azacitidine treatment generates oxidative stress in MDS patients, without affecting inflammation levels, suggesting that oxidative status and inflammation are two independent processes.

scholarly journals Imaging NAD(H) Redox Alterations in Cryopreserved Alveolar Macrophages from Ozone-Exposed Mice and the Impact of Nutrient Starvation during Long Lag Times

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 767
Author(s):  
He N. Xu ◽  
Joanna Floros ◽  
Lin Z. Li ◽  
Shaili Amatya
Keyword(s):  
Oxidative Stress ◽  
Alveolar Macrophages ◽  
Redox State ◽  
Redox Status ◽  
Nutrient Starvation ◽  
Ozone Exposure ◽  
Reduced Form ◽  
Time Period ◽  
Lag Times ◽  
The Impact

Employing the optical redox imaging technique, we previously identified a significant redox shift of nicotinamide adenine dinucleotide (NAD and the reduced form NADH) in freshly isolated alveolar macrophages (AM) from ozone-exposed mice. The goal here was twofold: (a) to determine the NAD(H) redox shift in cryopreserved AM isolated from ozone-exposed mice and (b) to investigate whether there is a difference in the redox status between cryopreserved and freshly isolated AM. We found: (i) AM from ozone-exposed mice were in a more oxidized redox state compared to that from filtered air (FA)-exposed mice, consistent with the results obtained from freshly isolated mouse AM; (ii) under FA exposure, there was no significant NAD(H) redox difference between fresh AM that had been placed on ice for 2.5 h and cryopreserved AM; however, under ozone exposure, fresh AM were more oxidized than cryopreserved AM; (iii) via the use of nutrient starvation and replenishment and H2O2-induced oxidative stress of an AM cell line, we showed that this redox difference between cryopreserved and freshly isolated AM is likely the result of the double “hit”, i.e., the ozone-induced oxidative stress plus nutrient starvation that prevented freshly isolated AM from a full recovery after being on ice for a prolonged time period. The cryopreservation technique we developed eliminates/minimizes the effects of oxidative stress and nutrient starvation on cells. This method can be adopted to preserve lung macrophages from animal models or clinical patients for further investigations.

Skeletal muscle uncoupling-induced longevity in mice is linked to increased substrate metabolism and induction of the endogenous antioxidant defense system

2013 ◽  
Vol 304 (5) ◽  
pp. E495-E506 ◽  
Author(s):  
S. Keipert ◽  
M. Ost ◽  
A. Chadt ◽  
A. Voigt ◽  
V. Ayala ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Antioxidant Defense ◽  
Antioxidant Defense System ◽  
Mapk Signaling ◽  
Redox Signaling ◽  
Defense System ◽  
High Fat ◽  
Substrate Metabolism ◽  
Endogenous Antioxidant

Ectopic expression of uncoupling protein 1 (UCP1) in skeletal muscle (SM) mitochondria increases lifespan considerably in high-fat diet-fed UCP1 Tg mice compared with wild types (WT). To clarify the underlying mechanisms, we investigated substrate metabolism as well as oxidative stress damage and antioxidant defense in SM of low-fat- and high-fat-fed mice. Tg mice showed an increased protein expression of phosphorylated AMP-activated protein kinase, markers of lipid turnover (p-ACC, FAT/CD36), and an increased SM ex vivo fatty acid oxidation. Surprisingly, UCP1 Tg mice showed elevated lipid peroxidative protein modifications with no changes in glycoxidation or direct protein oxidation. This was paralleled by an induction of catalase and superoxide dismutase activity, an increased redox signaling (MAPK signaling pathway), and increased expression of stress-protective heat shock protein 25. We conclude that increased skeletal muscle mitochondrial uncoupling in vivo does not reduce the oxidative stress status in the muscle cell. Moreover, it increases lipid metabolism and reactive lipid-derived carbonyls. This stress induction in turn increases the endogenous antioxidant defense system and redox signaling. Altogether, our data argue for an adaptive role of reactive species as essential signaling molecules for health and longevity.

scholarly journals Mineral Micronutrients in Asthma

Nutrients ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 4001
Author(s):  
Dominika Zajac
Keyword(s):  
Oxidative Stress ◽  
Risk Factors ◽  
Air Pollution ◽  
Defense Mechanisms ◽  
Redox Status ◽  
Chronic Inflammatory Disease ◽  
Modern World ◽  
Medical Issues ◽  
Persistent Inflammation ◽  
The Impact

Asthma represents one of the most common medical issues in the modern world. It is a chronic inflammatory disease characterized by persistent inflammation of the airways and disturbances in redox status, leading to hyperresponsiveness of bronchi and airway obstruction. Apart from classical risk factors such as air pollution, family history, allergies, or obesity, disturbances of the levels of micronutrients lead to impairments in the defense mechanisms of the affected organism against oxidative stress and proinflammatory stimuli. In the present review, the impact of micronutrients on the prevalence, severity, and possible risk factors of asthma is discussed. Although the influence of classical micronutrients such as selenium, copper, or zinc are well known, the effects of those such as iodine or manganese are only rarely mentioned. As a consequence, the aim of this paper is to demonstrate how disturbances in the levels of micronutrients and their supplementation might affect the course of asthma.

scholarly journals Redox Status in Women with Rheumathoid Arthritis

2018 ◽  
Vol 0 (0) ◽  
Author(s):  
Aleksandra Vranic ◽  
Aleksandra Antovic ◽  
Nevena Draginic ◽  
Marijana Andjic ◽  
Marko Ravic ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Lipid Peroxidation ◽  
Superoxide Dismutase ◽  
Cartilage Damage ◽  
Thiobarbituric Acid ◽  
Antioxidant Defense System ◽  
Redox Status ◽  
Female Population

Abstract The aim of this study was to assess oxidative status and to set baseline characteristics for female population with established rheumatoid arthritis. Total of 42 patients with rheumatoid arthritis and 48 age- and sex-matched controls were included in the study. Clinical examination was performed and assessed disease activity. Peripheral blood samples were used for all the assays. The markers of oxidative stress were assessed, including plasma levels of index of lipid peroxidation - thiobarbituric acid reactive substances, hydrogen peroxide, superoxide anion radical, nitrites and activity of superoxide dismutase, catalase and reduced glutathione levels as antioxidant parameters. In the patients group, levels of hydrogen peroxide and index of lipid peroxidation were higher than in controls. Patients with rheumatoid arthritis had decreased superoxide dismutase and catalase activity compared to healthy subjects. Interestingly, controls had higher levels of nitrites compared to patients. Patients showed a marked increase in reactive oxygen species formation and lipid peroxidation as well as decrease in the activity of antioxidant defense system leading to oxidative stress which may contribute to tissue and cartilage damage and hence to the chronicity of the disease.

scholarly journals Buprenorphine and Methadone as Opioid Maintenance Treatments for Heroin-Addicted Patients Induce Oxidative Stress in Blood

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Christonikos Leventelis ◽  
Nikolaos Goutzourelas ◽  
Aikaterini Kortsinidou ◽  
Ypatios Spanidis ◽  
Georgia Toulia ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Thiobarbituric Acid ◽  
Redox Status ◽  
Protein Carbonyls ◽  
Healthy Individuals ◽  
Thiobarbituric Acid Reactive Substances ◽  
Antioxidant Defence ◽  
Total Antioxidant ◽  
Beneficial Action ◽  
The Impact

Buprenorphine and methadone are two substances widely used in the substitution treatment of patients who are addicted to opioids. Although it is known that they partly act efficiently towards this direction, there is no evidence regarding their effects on the redox status of patients, a mechanism that could potentially improve their action. Therefore, the aim of the present investigation was to examine the impact of buprenorphine and methadone, which are administered as substitutes to heroin-dependent patients on specific redox biomarkers in the blood. From the results obtained, both the buprenorphine (n=21) and the methadone (n=21) groups exhibited oxidative stress and compromised antioxidant defence. This was evident by the decreased glutathione (GSH) concentration and catalase activity in erythrocytes and the increased concentrations of thiobarbituric acid reactive substances (TBARS) and protein carbonyls in the plasma, while there was no significant alteration of plasma total antioxidant capacity (TAC) compared to the healthy individuals (n=29). Furthermore, methadone revealed more severe oxidant action compared to buprenorphine. Based on relevant studies, the tested substitutes mitigate the detrimental effects of heroin on patient redox status; still it appears that they need to be boosted. Therefore, concomitant antioxidant administration could potentially enhance their beneficial action, and most probably, buprenorphine that did not induce oxidative stress in such a severe mode as methadone, on the regulation of blood redox status.

scholarly journals Brain Ageing, Cognition and Diet: A Review of the Emerging Roles of Food-Based Nootropics in Mitigating Age-related Memory Decline

2019 ◽  
Vol 12 (1) ◽  
pp. 2-14 ◽  
Author(s):  
Adejoke Yetunde Onaolapo ◽  
Adebimpe Yemisi Obelawo ◽  
Olakunle James Onaolapo
Keyword(s):  
Oxidative Stress ◽  
Cognitive Decline ◽  
Antioxidant Defense System ◽  
Food Ingredients ◽  
Memory Decline ◽  
Age Related ◽  
Brain Ageing ◽  
Nootropic Agents ◽  
Age Related Cognitive Decline ◽  
The Impact

Background: Age-related cognitive decline has been suggested to result from an increase in the brain neuron loss, which is attributable to continued derangement of the brain’s oxidant/ antioxidant balance. Increased oxidative stress and a concomitant decrease in the brain’s antioxidant defense system have been associated with functional senescence and organismal ageing. However, nature has configured certain foods to be rich sources of nootropic agents, with research showing that increased consumption of such foods or food ingredients may be protective against ageing-related memory decline. This knowledge is becoming increasingly valuable in an era when the boundary that separates food from medicine is becoming blurred. In this review, we examine extant literature dealing with the impact of ageing on brain structure and function, with an emphasis on the roles of oxidative stress. Secondly, we review the benefits of food-based antioxidants with nootropic effects and/or food-based nootropic agents in mitigating memory decline; with a view to improving our understanding of likely mechanisms. We also highlight some of the limitations to the use of food-based nootropics and suggest ways in which they can be better employed in the clinical management of age-related cognitive decline. Conclusion: While it is known that the human brain endures diverse insults in the process of ageing, food-based nootropics are likely to go a long way in mitigating the impacts of these insults. Further research is needed before we reach a point where food-based nootropics are routinely prescribed.

scholarly journals Changes in the Activity and Concentration of Superoxide Dismutase Isoenzymes (Cu/Zn SOD, MnSOD) in the Blood of Healthy Subjects and Patients with Acute Pancreatitis

Antioxidants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 948
Author(s):  
Milena Ściskalska ◽  
Monika Ołdakowska ◽  
Grzegorz Marek ◽  
Halina Milnerowicz
Keyword(s):  
Oxidative Stress ◽  
Acute Pancreatitis ◽  
Superoxide Dismutase ◽  
Healthy Subjects ◽  
Activity Concentration ◽  
Total Activity ◽  
Sod1 Gene ◽  
Markers Of Inflammation ◽  
Total Antioxidant ◽  
The Impact

This study was aimed at evaluating the changes in the concentration and activity of all superoxide dismutase isoenzymes (SOD1, SOD2, SOD3) in the blood of patients with acute pancreatitis (AP) and healthy subjects, taking into account the extracellular (plasma) and intracellular (erythrocyte lysate) compartment. The relationships between the activity/concentration of SODs, metal concentration and the markers of inflammation were evaluated. To assess the pro/antioxidative imbalance, the malonyldialdehyde (MDA) concentration and the value of total antioxidant capacity (TAC) were measured. The impact of single-nucleotide polymorphism (SNP) in the SOD1 gene (rs2070424) on the activity/concentration of SOD1 as the main isoenzyme of the SOD family was also analyzed in this study. The SOD2 activity in erythrocytes was increased compared to plasma: 10-fold in the AP patient group and 5-fold in healthy subjects. The plasma of AP patients showed an increased SOD1 concentration and decreased SOD2 and SOD3 concentrations compared to healthy subjects. The Cu/Zn SOD (SOD1 + SOD3) concentration in plasma of AP patients was elevated compared to healthy subjects, but changes in plasma Cu/Zn SOD (SOD1 + SOD3) activity in the examined groups were not observed. An influence of SNP rs2070424 in the SOD1 gene on the total activity of SOD in AP patients (with AG genotype), accompanied by an increased IL-6 concentration, was observed. In oxidative stress conditions induced by inflammation, the participation of individual forms of plasma SOD isoenzymes in total antioxidative activity of SOD changed. A significant increase in the intracellular SOD1 concentration in plasma of AP patients proves the important role of this isoenzyme in the neutralization of oxidative stress induced by impaired Cu and Zn homeostasis. The presence of increased concentration of SOD2 in erythrocytes of healthy subjects and AP patients confirms the important function of this isoenzyme in the antioxidative defense.

scholarly journals Whole-Body Cryotherapy Decreases the Levels of Inflammatory, Oxidative Stress, and Atherosclerosis Plaque Markers in Male Patients with Active-Phase Ankylosing Spondylitis in the Absence of Classical Cardiovascular Risk Factors

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Agata Stanek ◽  
Armand Cholewka ◽  
Tomasz Wielkoszyński ◽  
Ewa Romuk ◽  
Aleksander Sieroń
Keyword(s):  
Oxidative Stress ◽  
Risk Factors ◽  
Cardiovascular Risk ◽  
Ankylosing Spondylitis ◽  
Disease Activity ◽  
Cardiovascular Risk Factors ◽  
Whole Body ◽  
Markers Of Inflammation ◽  
Whole Body Cryotherapy ◽  
The Impact

Objective. The aim of the study was to estimate the impact of whole-body cryotherapy (WBC) on cardiovascular risk factors in patients with ankylosing spondylitis (AS). Material and Methods. We investigated the effect of WBC with subsequent kinesiotherapy on markers of inflammation, oxidative stress, lipid profile, and atherosclerosis plaque in male AS patients (WBC group). To assess the disease activity, the BASDAI and BASFI were also calculated. The results from the WBC group were compared with results from the kinesiotherapy (KT) group. Results. The results showed that in the WBC group, the plasma hsCRP level decreased without change to the IL-6 level. The ICAM-1 level showed a decreasing tendency. The CER concentration, as well as the BASDAI and BASFI, decreased in both groups, but the index changes of disease activity were higher in the WBC than KT patients. Additionally, in the WBC group, we observed a decrease in oxidative stress markers, changes in the activity of some antioxidant enzymes and nonenzymatic antioxidant parameters. In both groups, the total cholesterol and LDL cholesterol, triglycerides, sCD40L, PAPP-A, and PLGF levels decreased, but the parameter changes were higher in the WBC group. Conclusion. WBC appears to be a useful method of atherosclerosis prevention in AS patients.

ERCC1, KRAS mutation, redox status, and oxaliplatin sensitivity in colorectal cancer: “Radical” change in an old model.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14156-e14156
Author(s):  
Armando Orlandi ◽  
Mariantonietta Di Salvatore ◽  
Michele Basso ◽  
Cinzia Bagalà ◽  
Antonia Strippoli ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Cell Lines ◽  
Pearson Correlation ◽  
Redox Status ◽  
Mutational Status ◽  
Retrospective Clinical Study ◽  
Significant Difference ◽  
The Impact

e14156 Background: Oxaliplatin (Oxa) is widely used in metastatic colorectal cancer, but currently there are not valid predictors of response to this drug. In our recent retrospective clinical study we have shown a greater efficacy of Oxa in patients with metastatic colorectal cancer with mutated (mt) K-RAS. We hypothesized that the mutational status of K-RAS could influence the expression of ERCC1 and cellular Redox status. Methods: We used four cell lines of colorectal cancer: two K-RAS wild type (wt) (HCT-8, HT-29) and two K-RAS mt (SW620, SW480). We evaluated the sensitivity of these cell lines to Oxa by MTT-test and the ERCC1 levels before and after 24h exposure to Oxa by RT-PCR. We silenced K-RAS in a K-RAS mt cell lines to evaluate the impact on Oxa sensitivity and ERCC1 levels. We also silenced ERCC1 in order to confirm the importance of this protein as a Oxa resistance factor. Cellular oxidative stress was determined by DCFDA. Results: The K-RAS mt cell lines were more sensitive to Oxa (p<0.001). The basal levels of ERCC1 did not show significant differences between K-RAS mt and wt cell line, however, after 24h exposure to Oxa, only the K-RAS wt lines showed the ability to induce ERCC1, with a statistically significant difference (p<0.005). The silencing of K-RAS in K-RAS mt cell lines (SW620s) demonstrated to reduce sensitivity to Oxa associated with the acquisition of the ability to induce ERCC1. The silencing of ERCC1 in K-RAS wt cell lines enhance the sensibility to Oxa. The levels of reactive oxygen species were higher in K-RAS mt cell lines. The Pearson correlation test showed a statistically significant relationship between basal levels of ROS and sensitivity to Oxa ("r" -0,988, p<0.01). The baseline levels of ROS were higher SW620 than the line SW620s. The administration of Oxa in these cell lines resulted in a statistically higher fluorescence index in SW620 versus SW620s (p<0.003). Conclusions: The K-RAS mutated cell lines were more sensitive to Oxa. This feature seems to be secondary to the inability of these cells to induce ERCC1 after exposure to Oxa and to the synergism between K-RAS mutation and Oxa in increasing oxidative stress. K-RAS can thus be a predictor of response to Oxa in colorectal cancer.

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