Supplementation with uric and ascorbic acid protects stored red blood cells through enhancement of non-enzymatic antioxidant activity and metabolic rewiring
Vassilis L. Tzounakas,
Alkmini T. Anastasiadi,
Vasiliki-Zoi Arvaniti,
Veronica Lelli,
Giuseppina Fanelli,
Efthymios C. Paronis,
Anastasia C. Apostolidou,
Evangelos G. Balafas,
Nikolaos G. Kostomitsopoulos,
Effie G. Papageorgiou,
Issidora S. Papassideri,
Konstantinos Stamoulis,
Anastasios G. Kriebardis,
Sara Rinalducci,
Marianna H. Antonelou
Affiliations
Vassilis L. Tzounakas
Department of Biology, School of Science, National and Kapodistrian University of Athens (NKUA), Athens, Greece
Alkmini T. Anastasiadi
Department of Biology, School of Science, National and Kapodistrian University of Athens (NKUA), Athens, Greece
Vasiliki-Zoi Arvaniti
Department of Biology, School of Science, National and Kapodistrian University of Athens (NKUA), Athens, Greece
Veronica Lelli
Department of Ecological and Biological Sciences, University of Tuscia, Viterbo, Italy
Giuseppina Fanelli
Department of Ecological and Biological Sciences, University of Tuscia, Viterbo, Italy
Efthymios C. Paronis
Center of Clinical, Experimental Surgery & Translational Research, Biomedical Research Foundation, Academy of Athens (BRFAA), Athens, Greece
Anastasia C. Apostolidou
Center of Clinical, Experimental Surgery & Translational Research, Biomedical Research Foundation, Academy of Athens (BRFAA), Athens, Greece
Evangelos G. Balafas
Center of Clinical, Experimental Surgery & Translational Research, Biomedical Research Foundation, Academy of Athens (BRFAA), Athens, Greece
Nikolaos G. Kostomitsopoulos
Center of Clinical, Experimental Surgery & Translational Research, Biomedical Research Foundation, Academy of Athens (BRFAA), Athens, Greece
Effie G. Papageorgiou
Laboratory of Reliability and Quality Control in Laboratory Hematology (HemQcR), Department of Biomedical Sciences, School of Health & Welfare Sciences, University of West Attica (UniWA), Egaleo, Greece
Issidora S. Papassideri
Department of Biology, School of Science, National and Kapodistrian University of Athens (NKUA), Athens, Greece
Konstantinos Stamoulis
Hellenic National Blood Transfusion Centre, Acharnes, Greece
Anastasios G. Kriebardis
Laboratory of Reliability and Quality Control in Laboratory Hematology (HemQcR), Department of Biomedical Sciences, School of Health & Welfare Sciences, University of West Attica (UniWA), Egaleo, Greece
Sara Rinalducci
Department of Ecological and Biological Sciences, University of Tuscia, Viterbo, Italy; Corresponding author.
Marianna H. Antonelou
Department of Biology, School of Science, National and Kapodistrian University of Athens (NKUA), Athens, Greece; Corresponding author.
Redox imbalance and oxidative stress have emerged as generative causes of the structural and functional degradation of red blood cells (RBC) that happens during their hypothermic storage at blood banks. The aim of the present study was to examine whether the antioxidant enhancement of stored RBC units following uric (UA) and/or ascorbic acid (AA) supplementation can improve their storability as well as post-transfusion phenotypes and recovery by using in vitro and animal models, respectively. For this purpose, 34 leukoreduced CPD/SAGM RBC units were aseptically split in 4 satellite units each. UA, AA or their mixture were added in the three of them, while the fourth was used as control. Hemolysis as well as redox and metabolic parameters were studied in RBC units throughout storage. The addition of antioxidants maintained the quality parameters of stored RBCs, (e.g., hemolysis, calcium homeostasis) and furthermore, shielded them against oxidative defects by boosting extracellular and intracellular (e.g., reduced glutathione; GSH) antioxidant powers. Higher levels of GSH seemed to be obtained through distinct metabolic rewiring in the modified units: methionine-cysteine metabolism in UA samples and glutamine production in the other two groups. Oxidatively-induced hemolysis, reactive oxygen species accumulation and membrane lipid peroxidation were lower in all modifications compared to controls. Moreover, denatured/oxidized Hb binding to the membrane was minor, especially in the AA and mix treatments during middle storage. The treated RBC were able to cope against pro-oxidant triggers when found in a recipient mimicking environment in vitro, and retain control levels of 24h recovery in mice circulation. The currently presented study provides (a) a detailed picture of the effect of UA/AA administration upon stored RBCs and (b) insight into the differential metabolic rewiring when distinct antioxidant “enhancers” are used.
