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

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.

Why Does Hyperuricemia Not Necessarily Induce Gout?

“…UA is also a potent antioxidant and an effective scavenger of singlet oxygen and free radicals [ 34 ], almost tenfold greater than other antioxidants in blood [ 26 ] or accounting for over half of the free radical scavenging activity in vivo [ 35 ]. Supplement of UA in donor blood sustains the antioxidant protection of the stored red blood cells [ 36 ]. The oxidant-antioxidant paradox of UA [ 37 ] may suggest UA could have different molecular behaviors under various pathological conditions.…”

Image- and Fluorescence-Based Test Shows Oxidant-Dependent Damages in Red Blood Cells and Enables Screening of Potential Protective Molecules

“…It is indeed known that urate possesses antioxidant and pro-oxidant properties in hydrophilic and lipid environments, respectively [ 24 , 25 ]. It is for this reason that UA has been coupled to AA to prevent pro-oxidant effects [ 3 , 26 ]. Equivalent benefits on quenching ROS were reported with AA, trolox and resveratrol (fluorescence data).…”

“…Previous studies have explored the opportunity to compensate the apparition of oxidative stress by adding antioxidants (or precursors of them) in the preservative solution. The addition of AA, UA, precursors of glutathione or components such as vitamin E provided limited improvements of the storage lesions, whatever the parameters followed [ 1 , 3 , 4 , 5 , 6 ]. Investigators evaluated supplementation with ascorbate and urate (with the aim to restore normal plasma concentrations) in order to prevent the loss of antioxidant power (AOP) and metabolic dysregulation subsequent to blood products preparation [ 7 ].…”

“…Investigators evaluated supplementation with ascorbate and urate (with the aim to restore normal plasma concentrations) in order to prevent the loss of antioxidant power (AOP) and metabolic dysregulation subsequent to blood products preparation [ 7 ]. Despite the observed variations in metabolism, this treatment did not improve the “standard aging” parameters (i.e., such as morphology changes and hemolysis) [ 3 ]. Such mitigated results triggered the following reflections: (1) Are these compounds indeed protective against oxidative stress?…”

Why Hyperuricemia Does Not Necessarily Induce Gout?

“…UA also is a potent antioxidant and an effective scavenger of singlet oxygen and free radicals [34], almost tenfold greater than other antioxidants in blood [26] or accounting for over half of the free radical scavenging activity in vivo [35]. Supplement of UA in donor blood sustains the antioxidant protection of the stored red blood cells [36]. The oxidant-antioxidant paradox of UA [37] may suggest UA could have different molecular behaviours under various pathological conditions.…”