Restoration of Physiological Levels of Uric Acid and Ascorbic Acid Reroutes the Metabolism of Stored Red Blood Cells.

Manon Bardyn,Mario Jolicoeur,David Crettaz,Jingkui Chen,Emmanuel Längst,Pascal Amireault,Lucas Schmid,Jean-Daniel Tissot,Michel Prudent,Michaël Dussiot

doi:10.3390/metabo10060226

Abstract

After blood donation, the red blood cells (RBCs) for transfusion are generally isolated by centrifugation and then filtrated and supplemented with additive solution. The consecutive changes of the extracellular environment participate to the occurrence of storage lesions. In this study, the hypothesis is that restoring physiological levels of uric and ascorbic acids (major plasmatic antioxidants) might correct metabolism defects and protect RBCs from the very beginning of the storage period, to maintain their quality. Leukoreduced CPD-SAGM RBC concentrates were supplemented with 416 µM uric acid and 114 µM ascorbic acid and stored during six weeks at 4 °C. Different markers, i.e., haematological parameters, metabolism, sensitivity to oxidative stress, morphology and haemolysis were analyzed. Quantitative metabolomic analysis of targeted intracellular metabolites demonstrated a direct modification of several metabolite levels following antioxidant supplementation. No significant differences were observed for the other markers. In conclusion, the results obtained show that uric and ascorbic acids supplementation partially prevented the metabolic shift triggered by plasma depletion that occurs during the RBC concentrate preparation. The treatment directly and indirectly sustains the antioxidant protective system of the stored RBCs.

Highlights

The stress that red blood cells (RBCs) accumulate during their storagetriggers damages that can impair transfusion and are suspected to be associated with deleterious side effects, that could affect the patient’s clinical outcome [1,2,3,4,5]
RBC morphology analyzed by digital holographic microscopy (DHM) was not improved by the antioxidant treatment
Addition of protective molecules and/or modifications of the additive solution composition used for the storage of the labile blood products is probably one of the most convenient and cost-effective approaches to guarantee a product of good quality for all patients

Summary

Introduction

The stress that red blood cells (RBCs) accumulate during their storage (up to six weeks at 4 ◦ C)triggers damages that can impair transfusion and are suspected to be associated with deleterious side effects, that could affect the patient’s clinical outcome [1,2,3,4,5]. The stress that red blood cells (RBCs) accumulate during their storage (up to six weeks at 4 ◦ C). When storage duration is extended beyond four weeks, the RBC energetic, protective and repair systems are so profoundly affected that irreversible lesions begin to accumulate [7,8,9,10]. Behind the debate about the product safety, one should think about its quality It undoubtedly declines with storage duration because of the impairment of several biochemical and biological functions, impacting the transfusion efficiency. It feeds the debate in transfusion praxis related to the age of the products [5,12,14]

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Discussion

Conclusion