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Erythrocytes undergo several changes during human aging and age-related diseases and, thus, have been studied as biomarkers of the aging process. The present study aimed to explore the antioxidant ability of metal and metal oxide nanoparticles (NPs) such as iron oxide (Fe3O4), gold (Au), and silver (Ag) to mitigate age-related oxidative stress in human erythrocytes. Metal and metal oxide NPs behave like antioxidative enzymes, directly influencing redox pathways and thus have better efficiency. Additionally, biopolymer coatings such as dextran enhance the biocompatibility of these NPs. Therefore, dextran-coated Fe3O4, Au, and Ag NPs were synthesized using wet chemical methods and were characterized. Their hemocompatibility and ability to protect erythrocytes from age-induced oxidative stress were investigated. The Fe3O4 and Au NPs were observed to protect erythrocytes from hydrogen peroxide and age-induced oxidative damage, including decreased antioxidant levels, reduced activity of antioxidative enzymes, and increased amounts of oxidative species. Pretreatment with NPs preserved the morphology and membrane integrity of the erythrocyte. However, Ag NPs induced oxidative stress in erythrocytes similar to hydrogen peroxide. Therefore, dextran-coated Fe3O4 and Au nanoparticles have the potential to be employed as antioxidant therapies against age-related oxidative stress., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Red blood cells (RBCs) are usually considered simple cells and transporters of gases to tissues., Hypothesis: However, recent research has suggested that RBCs may have diagnostic potential in major neurodegenerative disorders (NDDs)., Results: This review summarizes the current knowledge on changes in RBC in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and other NDDs. It discusses the deposition of neuronal proteins like amyloid-β, tau, and α-synuclein, polyamines, changes in the proteins of RBCs like band-3, membrane transporter proteins, heat shock proteins, oxidative stress biomarkers, and altered metabolic pathways in RBCs during neurodegeneration. It also highlights the comparison of RBC diagnostic markers to other in-market diagnoses and discusses the challenges in utilizing RBCs as diagnostic tools, such as the need for standardized protocols and further validation studies., Significance Statement: The evidence suggests that RBCs have diagnostic potential in neurodegenerative disorders, and this study can pave the foundation for further research which may lead to the development of novel diagnostic approaches and treatments., (© 2024 Société Française des Microscopies and Société de Biologie Cellulaire de France. Published by John Wiley & Sons Ltd.)

Context: Oxidative stress plays a key role in the patho-physiology of hypertension. (-)-Epicatechin has many important biological properties., Objective: The present study was undertaken to evaluate effect of (-)-epicatechin on protein carbonyl content in gender-based hypertensive patients and normal subjects., Methods: The study was carried out on 83 normal (male: 42; female: 41) and 62 hypertensive subjects (male: 32; female: 30). In vitro effect on (-)-epicatechin and L-ascorbic acid was estimated on protein carbonyl content., Results: Result showed a significant (p < 0.001) increase in protein carbonyl content in hypertensive patients but no gender-based difference was observed. (-)-epicatechin shows significant (p < 0.001) dose-dependent effect as compared to L-ascorbic acid, which is manifested as decrease in protein carbonyl content., Conclusion: We hypothesizes that a higher intake of (-)-epicatechin may provide protection against hypertension in males and females.

Content: Quercetin uptake by erythrocytes is rapid. The sodium-hydrogen exchanger (NHE) is a secondary active transporter, regulating intracellular pH, Na(+) concentration and cell volume., Objective: The aim of present study was to investigate NHE as a function of human age and effect of quercetin on its activity. The NHE activity was correlated with erythrocytes ATPases., Materials and Methods: We analyzed normal, healthy subjects of both sexes (20-82 years). NHE activity was estimated in terms of amiloride-sensitive H+-efflux from acid-loaded cells., Results: A significant age-dependent increase in NHE activity was observed during aging in humans. Concentration (10(-3 )M to 10(-8 )M)-dependent in vitro treatment with quercetin causes inhibition of NHE activity. The Na(+)/K(+) -ATPase (r = 0.8882) and Ca(2+)-ATPase (r = 0.9540) activities positively correlated with it., Discussion and Conclusion: The present data show an additional mechanism where dietary flavonoids may exerts beneficial effect during aging.

Context: Glucose-6-phosphate dehydrogenase (G6PD) is an important enzyme of hexose monophosphate shunt, involved in the biosynthesis of reduced nicotinamide adenine dinucleotide phosphate hydrogen (NADPH)., Objective: This study was designed to investigate age-dependent changes in human erythrocyte G6PD activity. The G6PD activity pattern was correlated with reduced glutathione (GSH) and total antioxidant potential in terms of FRAP (ferric reducing ability of plasma) value., Materials and Methods: We analyzed normal, healthy subjects of both sexes between the ages of 20 and 80 years. G6PD activity was determined by Burties method., Results: We observe a significant age-dependent decrease in G6PD activity (p < 0.0001). It was positively correlated with GSH (r = 0.5706) and total antioxidant potential (r = 0.7723) as a function of human age., Discussion and Conclusion: Our findings on erythrocyte G6PD and their correlation with GSH and FRAP provide evidence of a higher oxidative stress in old age population.

Thiol compounds such as cysteine (Cys) and reduced glutathione (GSH) play an important role in human aging and age-related diseases. In erythrocytes, GSH is synthesized by glutamic acid, cysteine, and glycine, but the rate of GSH synthesis is determined only by the availability of L-cysteine. Cysteine supplementation has been shown to ameliorate several parameters that are known to degenerate during human aging. We have studied L-cysteine efflux in vitro in human erythrocytes as a function of age by suspending cells in solution containing 10 mM L-cysteine for uptake; later cells were re-suspended in phosphate-buffered saline (PBS)-glucose to allow efflux. Change in the free sulfhydryl (-SH) concentration was then measured to calculate the rate of efflux. The GSH/oxidized glutathione (GSSG) ratio was taken as a control to study the oxidation/reduction state of the erythrocyte. The total anti-oxidant potential of plasma was measured in terms of ferric reducing ability of plasma (FRAP) values. We have shown a significant (p<0.0001) decline in the efflux of L-cysteine in erythrocytes during human aging, and the GSH/GSSG ratio decreases as a function of human age. The decline in L-cysteine efflux during aging correlates with the decrease in GSH and the FRAP value. This finding may help to explain the shift in the redox status and low GSH concentration that might determine the rate of L-cysteine efflux observed in erythrocytes and an important factor in the development of oxidative stress in erythrocytes during aging.

The present studies were carried out to determine the intracellular uptake of (-)epicatechin by erythrocytes during aging in humans. (-)Epicatechin uptake was estimated by performing ethyl acetate extraction while the total antioxidant potential of the (-)epicatechin was estimated in terms of FRAP (ferric reducing ability of plasma) values. A significant (p < 0.001) decrease in (-)epicatechin uptake by human erythrocytes was observed as a function of age. It is hypothesized that the uptake of (-)epicatechin in human erythrocytes has an important role in the regulation of PMRS (plasma membrane redox system) activity during normal human aging., (Copyright © 2010 John Wiley & Sons, Ltd.)

Oxidative stress is believed to play a central role in aging and age-associated diseases. It leads to oxidative changes in human red blood cells (RBCs) in vivo and in vitro. In this study, we evaluated the oxidative damage to the erythrocytes during aging in the humans using RBC as a model, by measuring the cytosolic antioxidant enzyme glutathione peroxidase (GPx) activity. GPx activity was found to be significantly decreased as a function of human age and positively correlated with total antioxidant capacity, while negatively correlated with SOD activity. Thus, results of the present study showed involvement of oxidative stress as one of the risk factors, which can initiate and/or promote human aging.

Erythrocytes play a crucial role in recycling ascorbate in blood plasma. The erythrocyte ascorbate free radical (AFR) reductase is involved in the reduction of AFR to ascorbic acid (ASC) in the plasma. In the present study, we report an age-dependent increase in the activity of erythrocyte AFR reductase in humans that shows a significant positive correlation with the activity of plasma membrane redox system (PMRS). We explain the age-dependent increase in erythrocyte ASC recycling on the basis of a compensatory/protective mechanism that operates to maintain the ASC level in plasma and thereby minimize oxidative stress during aging.

Antioxidant effect of tea catechins has been shown in many epidemiological studies. In the present study we report the protective mechanism of tea catechins (EGCG, ECG, EGC, EC) on various oxidative stress parameters, which are elevated during aging in humans. We hereby report the in vitro effect of tea catechins on erythrocyte malondialdehyde (MDA), reduced glutathione (GSH), and on membrane sulphydryl (-SH) group in humans. Results show an age-dependent increase in erythrocyte MDA level and a decrease in GSH and membrane-SH group concentration. We report that tea catechins show significant protection to erythrocyte against oxidative stress induced by tert-butyl hydroperoxide (t-BHP). The effect was more pronounced in older age group compared to lower age group. The findings suggest a possible role of tea catechins as anti-aging compounds.

In erythrocytes, although three amino acids are required for the synthesis of reduced glutathione (GSH), the rate of GSH synthesis is determined only by the availability of L-cysteine. Cysteine supplementation has been shown to ameliorate several parameters that are known to degenerate during human aging; this has led to an interesting hypothesis that aging could be a cysteine deficiency syndrome. In the present study, we measured L-cysteine influx in human erythrocytes by suspending cells in solution containing 10 mM L-cysteine. We show a significant decline in the influx of L-cysteine in erythrocytes during aging in humans. The decrease in cysteine influx correlates with the decrease in antioxidant potential of plasma measured in terms of FRAP (ferric-reducing ability of plasma) during aging. We conclude that a decreased influx of L-cysteine may be an important factor contributing to the development of oxidative stress in human erythrocytes during aging.

The correlation between antioxidant capacity and oxidative damage during aging has been reported in several tissues in different species; however, data on changes of oxidative stress markers in plasma and erythrocytes of healthy populations during aging are few and sometimes contradictory. Since antioxidant capacity of the plasma is related to dietary intake of antioxidants, it is important to study the correlation between antioxidant capacity of the plasma and markers of oxidative stress in different populations. In the present study we report the age-dependent alteration in erythrocyte malondialdehyde (MDA), intracellular-reduced glutathione (GSH), and membrane sulphydryl (SH) groups in the Indian population and also correlate these parameters with total plasma antioxidant potential. We show an age-dependent increase in erythrocyte MDA level and a decrease in GSH and membrane -SH group concentration. The alterations in these parameters correlated significantly with total antioxidant capacity of the plasma. We observe a higher oxidative stress in the Indian population compared to values reported for European subjects emphasizing the need to establish age-dependent reference values for oxidative stress markers in different populations and in studies involving their role in different disease conditions.