Rapamycin alleviates oxidative stress-induced damage in rat erythrocytes

2016 ◽  
Vol 94 (5) ◽  
pp. 471-479 ◽  
Author(s):  
Abhishek Kumar Singh ◽  
Sandeep Singh ◽  
Geetika Garg ◽  
Syed Ibrahim Rizvi
Keyword(s):  
Oxidative Stress ◽  
Defense Mechanism ◽  
Osmotic Fragility ◽  
Redox System ◽  
Protein Carbonyl ◽  
Ros Production ◽  
Rat Erythrocytes ◽  
Immunosuppressant Drug ◽  
Reducing Ability ◽  
Intracellular Ca

An imbalanced cellular redox system promotes the production of reactive oxygen species (ROS) that may lead to oxidative stress-mediated cell death. Erythrocytes are the best-studied model of antioxidant defense mechanism. The present study was undertaken to investigate the effect of the immunosuppressant drug rapamycin, an inducer of autophagy, on redox balance of erythrocytes and blood plasma of oxidatively challenged rats. Male Wistar rats were oxidatively challenged with HgCl2 (5 mg/kg body mass (b.m.)). A significant (p < 0.05) induction in ROS production, plasma membrane redox system (PMRS), intracellular Ca2+ influx, lipid peroxidation (LPO), osmotic fragility, plasma protein carbonyl (PCO) content, and plasma advanced oxidation protein products (AOPP) and simultaneously significant reduction in glutathione (GSH) level and ferric reducing ability of plasma (FRAP) were observed in rats exposed to HgCl2. Furthermore, rapamycin (0.5 mg/kg b.m.) provided significant protection against HgCl2-induced alterations in rat erythrocytes and plasma by reducing ROS production, PMRS activity, intracellular Ca2+ influx, LPO, osmotic fragility, PCO content, and AOPP and also restored the level of antioxidant GSH and FRAP. Our observations provide evidence that rapamycin improves redox status and attenuates oxidative stress in oxidatively challenged rats. Our data also demonstrate that rapamycin is a comparatively safe immunosuppressant drug.

Exercise-induced oxidative stress leads hemolysis in sedentary but not trained humans

2005 ◽  
Vol 99 (4) ◽  
pp. 1434-1441 ◽  
Author(s):  
Ümit Kemal Şentürk ◽  
Filiz Gündüz ◽  
Oktay Kuru ◽  
Günnur Koçer ◽  
Yaşar Gül Özkaya ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Osmotic Fragility ◽  
Thiobarbituric Acid ◽  
Protein Carbonyl ◽  
Antioxidant Vitamin ◽  
Thiobarbituric Acid Reactive Substance ◽  
Protein Carbonyl Content ◽  
Trained Subjects ◽  
Exercise Induced ◽  
Sedentary Subjects

Intravascular hemolysis is one of the most emphasized mechanisms for destruction of erythrocytes during and after physical activity. Exercise-induced oxidative stress has been proposed among the different factors for explaining exercise-induced hemolysis. The validity of oxidative stress following exhaustive cycling exercise on erythrocyte damage was investigated in sedentary and trained subjects before and after antioxidant vitamin treatment (A, C, and E) for 2 mo. Exercise induced a significant increase in thiobarbituric acid-reactive substance and protein carbonyl content levels in sedentary subjects and resulted in an increase of osmotic fragility and decrease in deformability of erythrocytes, accompanied by signs for intravascular hemolysis (increase in plasma hemoglobin concentration and decrease in haptoglobulin levels). Administration of antioxidant vitamins for 2 mo prevented exercise-induced oxidative stress (thiobarbituric acid-reactive substance, protein carbonyl content) and deleterious effects of exhaustive exercise on erythrocytes in sedentary subjects. Trained subjects' erythrocyte responses to exercise were different from those of sedentary subjects before antioxidant vitamin treatment. Osmotic fragility and deformability of erythrocytes, plasma hemoglobin concentration, and haptoglobulin levels were not changed after exercise, although the increased oxidative stress was observed in trained subjects. After antioxidant vitamin treatment, functional and structural parameters of erythrocytes were not altered in the trained group, but exercise-induced oxidative stress was prevented. Increased percentage of young erythrocyte populations was determined in trained subjects by density separation of erythrocytes. These findings suggest that the exercise-induced oxidative stress may contribute to exercise-induced hemolysis in sedentary humans.

High-dose benfotiamine rescues cardiomyocyte contractile dysfunction in streptozotocin-induced diabetes mellitus

2006 ◽  
Vol 100 (1) ◽  
pp. 150-156 ◽  
Author(s):  
Asli F. Ceylan-Isik ◽  
Shan Wu ◽  
Qun Li ◽  
Shi-Yan Li ◽  
Jun Ren
Keyword(s):  
Oxidative Stress ◽  
Ventricular Myocytes ◽  
Electrical Stimulus ◽  
Protein Carbonyl ◽  
Left Ventricular ◽  
High Dose ◽  
Contractile Dysfunction ◽  
Maximal Velocity ◽  
Velocity Of Shortening ◽  
Intracellular Ca

Diabetic cardiomyopathy is characterized by cardiac dysfunction. This study was designed to examine the effect of benfotiamine, a lipophilic derivative of thiamine, on streptozotocin (STZ)-induced cardiac contractile dysfunction in mouse cardiomyocytes. Adult male FVB mice were made diabetic with a single injection of STZ (200 mg/kg ip). Fourteen days later, control and diabetic (fasting plasma glucose > 13.9 mM) mice were put on benfotiamine therapy (100 mg·kg−1·day−1 ip) for another 14 days. Mechanical and intracellular Ca2+ properties were evaluated in left ventricular myocytes using an IonOptix MyoCam system. The following indexes were evaluated: peak shortening (PS), time to PS (TPS), time to 90% relengthening (TR90), maximal velocity of shortening/relengthening, resting and rise of intracellular Ca2+ in response to electrical stimulus, sarcoplasmic reticulum (SR) Ca2+ load, and intracellular Ca2+ decay rate (τ). Two- or four-week STZ treatment led to hyperglycemia, prolonged TPS and TR90, reduced SR Ca2+ load, elevated resting intracellular Ca2+ level and prolonged τ associated with normal PS, maximal velocity of shortening/relengthening, and intracellular Ca2+ rise in response to electrical stimulus. Benfotiamine treatment abolished prolongation in TPS, TR90, and τ, as well as reduction in SR Ca2+ load without affecting hyperglycemia and elevated resting intracellular Ca2+. Diabetes triggered oxidative stress, measured by GSH-to-GSSG ratio and formation of advanced glycation end product (AGE) in the hearts. Benfotiamine treatment alleviated oxidative stress without affecting AGE or protein carbonyl formation. Collectively, our results indicated that benfotiamine may rescue STZ-induced cardiomyocyte dysfunction but not AGE formation in short-term diabetes.

scholarly journals Paraoxonases-2 and -3 Are Important Defense Enzymes againstPseudomonas aeruginosaVirulence Factors due to Their Anti-Oxidative and Anti-Inflammatory Properties

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Eva-Maria Schweikert ◽  
Julianna Amort ◽  
Petra Wilgenbus ◽  
Ulrich Förstermann ◽  
John F. Teiber ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Defense Mechanism ◽  
Homoserine Lactone ◽  
Host Cells ◽  
Defense System ◽  
Innate Defense ◽  
Redox Active ◽  
Intracellular Ca ◽  
Anti Inflammatory ◽  
Underlying Mechanisms

The pathogenPseudomonas aeruginosacauses serious damage in immunocompromised patients by secretion of various virulence factors, among them the quorum sensing N-(3-oxododecanoyl)-L-homoserine lactone (3OC12) and the redox-active pyocyanin (PCN). Paraoxonase-2 (PON2) may protect againstP. aeruginosainfections, as it efficiently inactivates 3OC12 and diminishes PCN-induced oxidative stress. This defense could be circumvented because 3OC12 mediates intracellular Ca2+-rise in host cells, which causes rapid inactivation and degradation of PON2. Importantly, we recently found that the PON2 paralogue PON3 prevents mitochondrial radical formation. Here we investigated its role as additional potential defense mechanism againstP. aeruginosainfections. Our studies demonstrate that PON3 diminished PCN-induced oxidative stress. Moreover, it showed clear anti-inflammatory potential by protecting against NF-κB activation and IL-8 release. The latter similarly applied to PON2. Furthermore, we observed a Ca2+-mediated inactivation and degradation of PON3, again in accordance with previous findings for PON2. Our results suggest that the anti-oxidative and anti-inflammatory functions of PON2 and PON3 are an important part of our innate defense system againstP. aeruginosainfections. Furthermore, we conclude thatP. aeruginosacircumvents PON3 protection by the same pathway as for PON2. This may help identifying underlying mechanisms in order to sustain the protection afforded by these enzymes.

scholarly journals Acute Effects of Triathlon Race on Oxidative Stress Biomarkers

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Simona Mrakic-Sposta ◽  
Maristella Gussoni ◽  
Alessandra Vezzoli ◽  
Cinzia Dellanoce ◽  
Mario Comassi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Thiobarbituric Acid ◽  
Redox Status ◽  
Protein Carbonyl ◽  
Strenuous Exercise ◽  
Ros Production ◽  
Oxidative Stress Biomarkers ◽  
Training Time ◽  
Training Activity ◽  
Inflammatory Parameters

The response to strenuous exercise was investigated by reactive oxygen species (ROS) production, oxidative damage, thiol redox status, and inflammation assessments in 32 enrolled triathlon athletes (41.9±7.9 yrs) during Ironman® (IR), or half Ironman® (HIR) competition. In biological samples, inflammatory cytokines, aminothiols (glutathione (GSH), homocysteine (Hcy), cysteine (Cys), and cysteinylglycine (CysGly)), creatinine and neopterin, oxidative stress (OxS) biomarkers (protein carbonyl (PC), thiobarbituric acid-reactive substances (TBARS)), and ROS were assessed. Thirteen HIR and fourteen IR athletes finished the race. Postrace, ROS (HIR +20%; IR +28%; p<0.0001), TBARS (HIR +57%; IR +101%), PC (HIR +101%; IR +130%) and urinary neopterin (HIR +19%, IR +27%) significantly (range p<0.05-0.0001) increased. Moreover, HIR showed an increase in total Cys +28%, while IR showed total aminothiols, Cys, Hcy, CysGly, and GSH increase by +48, +30, +58, and +158%, respectively (range p<0.05-0.0001). ROS production was significantly correlated with TBARS and PC (R2=0.38 and R2=0.40; p<0.0001) and aminothiols levels (range R2=0.17-0.47; range p<0.01-0.0001). In particular, ROS was directly correlated with the athletes’ age (R2=0.19; p<0.05), with ultraendurance years of training (R2=0.18; p<0.05) and the days/week training activity (R2=0.16; p<0.05). Finally, the days/week training activity (hours/in the last 2 weeks) was found inversely correlated with the IL-6 postrace (R2=‐0.21; p<0.01). A strenuous performance, the Ironman® distance triathlon competition, alters the oxidant/antioxidant balance through a great OxS response that is directly correlated to the inflammatory parameters; furthermore, the obtained data suggest that an appropriate training time has to be selected in order to achieve the lowest ROS production and IL-6 concentration at the same time.

scholarly journals PSXI-14 Supplementation with a blend containing Baccharis dracunculifolia and Tamarindus indica improve the oxidative state of steers in finishing phase

2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 400-401
Author(s):  
Vicente A Diaz Avila ◽  
Edineia Bonin ◽  
Venício M Carvalho ◽  
Lucas Stafuza Moreira ◽  
Jurandir Fernando Comar ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Thiobarbituric Acid ◽  
Protein Carbonyl ◽  
Oxidative Status ◽  
Carbonyl Groups ◽  
Tamarindus Indica ◽  
Plasma Parameters ◽  
Protein Carbonyl Groups ◽  
Reducing Ability ◽  
Oxidative State

Abstract Tissue oxidative stress has been associated with low productivity of beef cattle. Supplementation of animals with natural antioxidants added to the diet may be an alternative to improve the tissue oxidative status and the productivity of steers at finishing phase. The present study evaluated whether the addition to the diet of a blend (Mix) containing Baccharis dracunculifolia (40%), Tamarindus indica seed (40%), cashew nutshell oil (10%) and clove oil (10%) modifies the oxidative state in the plasma and liver of steers (Angus x Zebu) in finishing phase. Forty animals were randomly distributed into four groups (ten animal per group), which received Mix respectively at the daily dose of 0.0, 2.0, 4.0 and 6.0 g per animal during 84 days. Blood and liver were taken at slaughter of the animals. Blood samples were also taken before starting the supplementation and served as control. The ferric reducing ability of plasma (FRAP), thiol groups and protein carbonyl groups were measured as plasma parameters of oxidative stress. The levels of thiobarbituric acid reactive substances (TBARS), protein carbonyl groups, reactive oxygen species (ROS), glutathione and the activity of catalase and superoxide dismutase (SOD) were measured as hepatic parameter of oxidative stress. Plasma levels of protein carbonyl groups were 30% lower in the animals supplemented with 4.0 and 6.0 g Mix and FRAP was 20% higher in the animals supplemented with 6.0 g Mix (P &lt; 0.05; compared to the 0.0 g). Hepatic levels of TBARS were 38% lower in animals supplemented with 6.0 g Mix (P &lt; 0.05). The other parameters were not modified. In conclusion, the supplementation of steers with Mix improved the systemic oxidative status and may be a complementary alternative to the diet of these animals in the termination phase.

Redox modulating effects of grape juice during aging

2019 ◽  
Vol 31 (3) ◽  
Author(s):  
Raushan Kumar ◽  
Sukanya Bhoumik ◽  
Syed Ibrahim Rizvi
Keyword(s):  
Osmotic Fragility ◽  
Grape Juice ◽  
Redox System ◽  
Group Iv ◽  
Group Iii ◽  
Positive Effects ◽  
Reducing Ability ◽  
Group I ◽  
Male Wistar Rats ◽  
Old Rats

AbstractBackgroundPolyphenols are known because of their phytochemical constituents having antioxidative properties. In this regard, grape juice is highly enriched with polyphenolic constituents, and its supplementation has been known to improve many health and age-associated diseases and risk factors. Our study was entirely dedicated to evaluating the positive effects of grape juice on young and old rats’ erythrocytes and plasma.MethodsYoung (4 months) and old (24 months) male Wistar rats were given an oral dose of grape juice for 28 days. They were grouped into four categories (n = 6): Group I: young control rats; Group II: young grape juice treated rats; Group III: old control rats; Group IV: old treated rats. The treated groups were administered with 10 μL/g of grape juice according to body weight. The following biomarkers of antioxidant defense were measured: ferric reducing ability of plasma (FRAP), reactive oxygen species (ROS), plasma membrane redox system (PMRS), glutathione (GSH), osmotic fragility, and the decrease in lipid peroxidation measured in terms of malondialdehyde (MDA) levels.ResultsA significant increase (p<0.05) in antioxidant levels of FRAP, PMRS, and GSH and a significant decrease (p<0.05) in oxidized products such as ROS and MDA were seen in the treated rats in comparison to the controls. The decrease in ROS and rise in FRAP and PMRS levels suggest the ability of grape juice to combat oxidative stress effectively.ConclusionWe propose the role of grape juice as a potent antioxidant because of its easy bioavailability and its role in combating stress. Our results also approve grape juice as a possible antiaging agent.

scholarly journals The Redox Balance and Membrane Shedding in RBC Production, Maturation, and Senescence

2021 ◽  
Vol 12 ◽  
Author(s):  
Eitan Fibach
Keyword(s):  
Oxidative Stress ◽  
Blood Cells ◽  
Redox System ◽  
Redox Balance ◽  
Reticuloendothelial System ◽  
Cellular Processes ◽  
Membrane Cytoskeleton ◽  
Intracellular Ca ◽  
Membrane Shedding ◽  
Cellular Components

Membrane shedding in the form of extracellular vesicles plays a key role in normal physiology and pathology. Partial disturbance of the membrane–cytoskeleton linkage and increased in the intracellular Ca content are considered to be mechanisms underlying the process, but it is questionable whether they constitute the primary initiating steps. Homeostasis of the redox system, which depends on the equilibrium between oxidants and antioxidants, is crucial for many cellular processes. Excess oxidative power results in oxidative stress, which affects many cellular components, including the membrane. Accumulating evidence suggests that oxidative stress indirectly affects membrane shedding most probably by affecting the membrane–cytoskeleton and the Ca content. In red blood cells (RBCs), changes in both the redox system and membrane shedding occur throughout their life—from birth—their production in the bone marrow, to death—aging in the peripheral blood and removal by macrophages in sites of the reticuloendothelial system. Both oxidative stress and membrane shedding are disturbed in diseases affecting the RBC, such as the hereditary and acquired hemolytic anemias (i.e., thalassemia, sickle cell anemia, and autoimmune hemolytic anemia). Herein, I review some data-based and hypothetical possibilities that await experimental confirmation regarding some aspects of the interaction between the redox system and membrane shedding and its role in the normal physiology and pathology of RBCs.

scholarly journals Protective effects of dapagliflozin against oxidative stress-induced cell injury in human proximal tubular cells

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0247234
Author(s):  
Nawel Zaibi ◽  
Pengyun Li ◽  
Shang-Zhong Xu
Keyword(s):  
Oxidative Stress ◽  
Cell Proliferation ◽  
Cell Injury ◽  
Ros Production ◽  
Protective Effects ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Mitochondrial Ros ◽  
Intracellular Ca ◽  
Proximal Tubular

Elevated reactive oxygen species (ROS) in type 2 diabetes cause cellular damage in many organs. Recently, the new class of glucose-lowering agents, SGLT-2 inhibitors, have been shown to reduce the risk of developing diabetic complications; however, the mechanisms of such beneficial effect are largely unknown. Here we aimed to investigate the effects of dapagliflozin on cell proliferation and cell death under oxidative stress conditions and explore its underlying mechanisms. Human proximal tubular cells (HK-2) were used. Cell growth and death were monitored by cell counting, water-soluble tetrazolium-1 (WST-1) and lactate dehydrogenase (LDH) assays, and flow cytometry. The cytosolic and mitochondrial (ROS) production was measured using fluorescent probes (H2DCFDA and MitoSOX) under normal and oxidative stress conditions mimicked by addition of H2O2. Intracellular Ca2+ dynamics was monitored by FlexStation 3 using cell-permeable Ca2+ dye Fura-PE3/AM. Dapagliflozin (0.1–10 μM) had no effect on HK-2 cell proliferation under normal conditions, but an inhibitory effect was seen at an extreme high concentration (100 μM). However, dapagliflozin at 0.1 to 5 μM showed remarkable protective effects against H2O2-induced cell injury via increasing the viable cell number at phase G0/G1. The elevated cytosolic and mitochondrial ROS under oxidative stress was significantly decreased by dapagliflozin. Dapagliflozin increased the basal intracellular [Ca2+]i in proximal tubular cells, but did not affect calcium release from endoplasmic reticulum and store-operated Ca2+ entry. The H2O2-sensitive TRPM2 channel seemed to be involved in the Ca2+ dynamics regulated by dapagliflozin. However, dapagliflozin had no direct effects on ORAI1, ORAI3, TRPC4 and TRPC5 channels. Our results suggest that dapagliflozin shows anti-oxidative properties by reducing cytosolic and mitochondrial ROS production and altering Ca2+ dynamics, and thus exerts its protective effects against cell damage under oxidative stress environment.

scholarly journals Oxidative Stress Assessment in Response to Ultraendurance Exercise: Thiols Redox Status and ROS Production according to Duration of a Competitive Race

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Alessandra Vezzoli ◽  
Cinzia Dellanoce ◽  
Simona Mrakic-Sposta ◽  
Michela Montorsi ◽  
Sarah Moretti ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
High Performance ◽  
Thiobarbituric Acid ◽  
Exercise Duration ◽  
Redox Status ◽  
Protein Carbonyl ◽  
Ros Production ◽  
Paramagnetic Resonance ◽  
Total Antioxidant ◽  
Blood And Urine Samples

Purpose. Response to an ultraendurance competitive race on thiols redox status, reactive oxygen species (ROS) production, and oxidative stress (OxS) was investigated according to duration.Methods. Twenty-four elite runners were examined: six completed 50 km and eighteen 100 km. Blood and urine samples were collected before and immediately after the race. Erythrocytes and plasma aminothiols by high-performance liquid chromatography, total antioxidant capacity (TAC), and OxS biomarkers (protein carbonyl (PC), thiobarbituric acid-reactive substances (TBARS), 8-isoprostane (8-iso-PGF2α), and 8-OH-2-deoxyguanosine (8-OH-dG)) by immunoenzymatic assays and ROS production by Electron Paramagnetic Resonance were assessed.Results. Significant increases (Pbetween <0.05 and <0.0001) were recorded in plasma total and oxidized aminothiols concentration and TAC (P<0.0001) only after 100 km: plasmatic (ROS production (+12 versus +29%), PC (+54 versus +115%), and TBARS (+28 versus +55%)) and urinary (8-OH-dG.creatinine−1(+71 versus +158%) and 8-iso-PGF2α.creatinine−1(+43 versus +135%)) concentrations for 50 and 100 km (duration 4 h 3′ versus 8 h 42′), respectively.Conclusion. Very prolonged ultraendurance exercise causes an increase in ROS production and OxS depending on specific biomarker examined but always linearly and directly related to exercise duration. Redox status of erythrocytes was preserved. A relationship between running performance and both prerace ROS production and antioxidant-redox status was found in 100 km race.

Organochlorine pesticide residue levels and oxidative stress in preterm delivery cases

2010 ◽  
Vol 29 (5) ◽  
pp. 351-358 ◽  
Author(s):  
Rahul Pathak ◽  
Sanvidhan G Suke ◽  
Tanzeel Ahmed ◽  
Rafat S Ahmed ◽  
AK Tripathi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cord Blood ◽  
Preterm Delivery ◽  
Maternal Blood ◽  
Protein Carbonyl ◽  
Blood Levels ◽  
Organochlorine Pesticide Residue ◽  
Stress Markers ◽  
Reducing Ability ◽  
Full Term Delivery

A number of studies have focused attention on various biochemical abnormalities evoked due to exposure to organochlorine pesticides (OCPs). The aim of the present study was to analyze the OCP residues in maternal and cord blood of women and assess the levels of different non-enzymatic oxidative stress markers as well as to establish correlation with OCP levels, if any. Thirty women in each group of full-term delivery (FTD; ≥37 weeks of gestation) and preterm delivery (PTD; <37 weeks of gestation) were enrolled in this study. Levels of OCPs like Hexachlorocyclohexane (HCH), endosulfan, p,p′ Dichlorodiphenyldichloroethylene (DDE) and p,p’ Dichlorodiphenyltrichloroethane (DDT) were analyzed by gas chromatography. Non-enzymatic oxidative stress was measured by the quantification of malondialhyde (MDA), protein carbonyl, reduced glutathione (GSH) and ferric-reducing ability of plasma (FRAP). MDA and protein carbonyl levels were increased significantly, while the levels of GSH and FRAP were decreased in PTD in comparison to FTD cases. We have observed higher levels of β-HCH and α-endosulfan and increased oxidative stress in PTD than FTD cases. In PTD cases, a significant positive correlation was observed between maternal blood levels of β-HCH and MDA (r = .78), β-HCH and GSH (r = —.65), γ-HCH and MDA (r = .89), γ-HCH and GSH (r = —.74) and α-endosulfan and MDA (r = .54) in PTD cases. We also found significant correlations between cord blood levels of β-HCH and MDA (r = .59), β-HCH and GSH (r = —.69), γ-HCH and MDA (r = .62) and α-endosulfan and MDA (r = .54) in PTD cases. In conclusion, our results suggest that higher levels of some of the OCP residues may be associated with PTD and increased oxidative stress.

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