Supplementation with uric and ascorbic acid protects stored red blood cells through enhancement of non-enzymatic antioxidant activity and metabolic rewiring

Tzounakas, Vassilis L.; Anastasiadi, Alkmini T.; Arvaniti, Vasiliki-Zoi; Lelli, Veronica; Fanelli, Guido; Paronis, Efthymios; Apostolidou, Anastasia; Balafas, Evangelos; Kostomitsopoulos, Nikolaos; Papageorgiou, Effie; Papassideri, Issidora S.; Stamoulis, Konstantinos; Kriebardis, Anastasios G.; Rinalducci, Sara; Antonelou, Marianna H.

doi:10.1016/j.redox.2022.102477

Cited by 17 publications

(21 citation statements)

References 89 publications

(112 reference statements)

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“…The present study reflects a secondary correlation analysis of data derived from a previously reported RBC unit supplementation protocol ( Tzounakas et al, 2022 ), which focused on between-group differences in physiological and metabolic parameters. In that study, thirty-four leukoreduced RBC units from healthy individuals containing citrate-phosphate-dextrose (CPD)/saline-adenine-glucose-mannitol (SAGM) were split under aseptic conditions into four subunits of equal volume.…”

Section: Methodsmentioning

confidence: 99%

“…As previously stated ( Tzounakas et al, 2022 ), measurement of hemolysis (spontaneous, osmotic, mechanical, and oxidative lysis), intracellular reactive oxygen species (ROS), membrane lipid peroxidation and extracellular antioxidant capacity were performed in all samples. A selection of six samples per category provided metabolomic, proteasomal, and immunodetection data.…”

Section: Methodsmentioning

confidence: 99%

“…The levels of intracellular ROS were fluorometrically assessed using the redox-sensitive probe 5-(and-6)-chloromethyl-2′,7′-dichloro-dihydrofluoresceindiacetate, acetyl ester (CM-H 2 DCFDA) with and without external stimuli (tert-butyl hydroperoxide–tBHP; 100 μM). Malondialdehyde was detected at 532 nm post formation of a chromogenic complex with thiobarbituric acid ( Tzounakas et al, 2022 ), whereas extracellular antioxidant capacity (total, UA-dependent, and UA-independent) was evaluated via the ferric reducing antioxidant power (FRAP) assay ( Benzie and Strain, 1996 ).…”

Section: Methodsmentioning

confidence: 99%

“…Antioxidant enhancement to deal with the elevated oxidative stress during storage is a common effort to achieve this goal ( Amen et al, 2017 ; Barzegar et al, 2022 ; Nemkov et al, 2022 ). Uric (UA) and ascorbic acid (AA) are efficient natural antioxidants, the effect of which upon stored RBCs has been studied both distinctly ( Dawson et al, 1980 ; Raval et al, 2013 ; Sanford et al, 2017 ; Tzounakas et al, 2022 ) and in combination ( Bardyn et al, 2020 ; Tzounakas et al, 2022 ). A recent study by our team has shown that the addition of the two antioxidants ultimately mitigates oxidative lesions in RBCs, as exemplified by reduced oxidative lysis and membrane oxidation, and induces glutathione (GSH) synthesis through metabolic rerouting ( Tzounakas et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

“…Uric (UA) and ascorbic acid (AA) are efficient natural antioxidants, the effect of which upon stored RBCs has been studied both distinctly ( Dawson et al, 1980 ; Raval et al, 2013 ; Sanford et al, 2017 ; Tzounakas et al, 2022 ) and in combination ( Bardyn et al, 2020 ; Tzounakas et al, 2022 ). A recent study by our team has shown that the addition of the two antioxidants ultimately mitigates oxidative lesions in RBCs, as exemplified by reduced oxidative lysis and membrane oxidation, and induces glutathione (GSH) synthesis through metabolic rerouting ( Tzounakas et al, 2022 ). nonetheless, it has not been yet shown how the supplementation affects intra- and inter-associations between the levels of physiological and metabolic parameters throughout storage.…”

Section: Introductionmentioning

confidence: 99%

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The time-course linkage between hemolysis, redox, and metabolic parameters during red blood cell storage with or without uric acid and ascorbic acid supplementation

Anastasiadi

Stamoulis²,

Papageorgiou

et al. 2023

Front. Aging

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Oxidative phenomena are considered to lie at the root of the accelerated senescence observed in red blood cells (RBCs) stored under standard blood bank conditions. It was recently shown that the addition of uric (UA) and/or ascorbic acid (AA) to the preservative medium beneficially impacts the storability features of RBCs related to the handling of pro-oxidant triggers. This study constitutes the next step, aiming to examine the links between hemolysis, redox, and metabolic parameters in control and supplemented RBC units of different storage times. For this purpose, a paired correlation analysis of physiological and metabolism parameters was performed between early, middle, and late storage in each subgroup. Strong and repeated correlations were observed throughout storage in most hemolysis parameters, as well as in reactive oxygen species (ROS) and lipid peroxidation, suggesting that these features constitute donor-signatures, unaffected by the diverse storage solutions. Moreover, during storage, a general “dialogue” was observed between parameters of the same category (e.g., cell fragilities and hemolysis or lipid peroxidation and ROS), highlighting their interdependence. In all groups, extracellular antioxidant capacity, proteasomal activity, and glutathione precursors of preceding time points anticorrelated with oxidative stress lesions of upcoming ones. In the case of supplemented units, factors responsible for glutathione synthesis varied proportionally to the levels of glutathione itself. The current findings support that UA and AA addition reroutes the metabolism to induce glutathione production, and additionally provide mechanistic insight and footing to examine novel storage optimization strategies.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The time-course linkage between hemolysis, redox, and metabolic parameters during red blood cell storage with or without uric acid and ascorbic acid supplementation

Anastasiadi

Stamoulis²,

Papageorgiou

et al. 2023

Front. Aging

Self Cite

View full text Add to dashboard Cite

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Nanomaterial‐Enhanced Red Blood Cell Biopreservation: From Refrigeration to Cryopreservation

Xu,

Lei,

Zhu

2024

ChemBioChem

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Red blood cell (RBC) transfusions represent a cornerstone of clinical practice, with RBCs constituting the primary component in transfusion therapy. Extending the preservation of RBCs while maintaining their functional integrity would offer considerable advancements for both transfusion medicine and military healthcare. Despite decades of research, progress in achieving long‐term RBC preservation has been limited. A key challenge is the range of physical and biochemical damage RBCs incur during storage, leading to marked changes in their morphology, physiological function, and viability. While traditional preservation techniques have provided partial mitigation of these damages, their efficacy remains suboptimal. In contrast, nanomaterials, with their distinctive spatial architectures and surface properties, offer a promising avenue for minimizing storage‐related damage and extending RBC preservation. This review provides an overview of the major categories of damage encountered during RBC biopreservation, classified into storage lesions and cryolesions. We also highlight the key role of nanomaterials in enhancing the storage quality of RBCs and prolonging their preservation duration. Finally, we discuss the current challenges and pressing issues faced by nanomaterial‐based RBCs biopreservation.

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Cellular antioxidant activity measurement: An alternative to chemical antioxidant methods?

Granato

2023

Food Safety and Health

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Oxidative stress occurs when the production of reactive oxygen species (ROS) overpasses their degradation and buffering by endogenous antioxidants and those derived from the diet (exogenous antioxidants). In food science and nutrition, assessing antioxidant activity relies on chemical reactions—chemical test‐tube assays—and human and murine cell lines. Usually, an ROS inductor, such as hydrogen peroxide (H2O2) or peroxyl radicals (ROO•), is used to induce oxidation. Some biomarkers related to endogenous protection (i.e., catalase, superoxide dismutase, and glutathione reductase), oxidation‐end products (i.e., malondialdehyde), and intracellular ROS generation can be quantitatively determined. Herein, some insights into using human cell lines and related biomarkers are described, and the downsides of using chemical antioxidant assays are explained. In conclusion, research on antioxidants should be based on using relevant human cell cultures. In contrast, chemical antioxidant assays should be limited to an initial screening as their physiological importance is negligible.

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Supplementation with uric and ascorbic acid protects stored red blood cells through enhancement of non-enzymatic antioxidant activity and metabolic rewiring

Cited by 17 publications

References 89 publications

The time-course linkage between hemolysis, redox, and metabolic parameters during red blood cell storage with or without uric acid and ascorbic acid supplementation

The time-course linkage between hemolysis, redox, and metabolic parameters during red blood cell storage with or without uric acid and ascorbic acid supplementation

Nanomaterial‐Enhanced Red Blood Cell Biopreservation: From Refrigeration to Cryopreservation

Cellular antioxidant activity measurement: An alternative to chemical antioxidant methods?

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