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Review
. 2023 Aug 18;13(8):1262.
doi: 10.3390/biom13081262.

Oxidative Stress in Healthy and Pathological Red Blood Cells

Affiliations
Review

Oxidative Stress in Healthy and Pathological Red Blood Cells

Florencia Orrico et al. Biomolecules. .

Abstract

Red cell diseases encompass a group of inherited or acquired erythrocyte disorders that affect the structure, function, or production of red blood cells (RBCs). These disorders can lead to various clinical manifestations, including anemia, hemolysis, inflammation, and impaired oxygen-carrying capacity. Oxidative stress, characterized by an imbalance between the production of reactive oxygen species (ROS) and the antioxidant defense mechanisms, plays a significant role in the pathophysiology of red cell diseases. In this review, we discuss the most relevant oxidant species involved in RBC damage, the enzymatic and low molecular weight antioxidant systems that protect RBCs against oxidative injury, and finally, the role of oxidative stress in different red cell diseases, including sickle cell disease, glucose 6-phosphate dehydrogenase deficiency, and pyruvate kinase deficiency, highlighting the underlying mechanisms leading to pathological RBC phenotypes.

Keywords: antioxidant; erythrocyte; glucose 6-phosphate dehydrogenase deficiency; oxidative stress; pyruvate kinase deficiency; reactive oxygen species; sickle cell disease.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Scheme summarizing main endogenous and exogenous sources of ROS and RNS in the RBCs as well as the principal antioxidant actors. HbO2: Oxyhemoglobin; MetHb: methemoglobin; O2•−: superoxide anion; NO: nitric oxide; H2O2: hydrogen peroxyde; ONOO-: peroxynitrite; HO: hydroxyl radical; HOCl: hypochlorous acid; CO3•−: carbonate radical; NO2: nitrogen dioxide radical; superoxide dismutase: SOD; catalase: Cat; glutathione reductase: GR; reduced glutathione: GSH; glutathione peroxidase 1: Gpx1; thioredoxin reductase: TR; thioredoxin: Trx; Peroxiredoxin 2: Prx2.
Figure 2
Figure 2
Scheme of main mechanism involved in oxidative stress and hemolytic clinical manifestations in Sickle Cell Disease, G6PDH deficiency, and PK deficiency. In SCD, highly unstable HbS will be converted in MetHb, favoring band 3 clustering and dissociation from membrane complexes, inducing membrane disorganization and membrane fragility. In G6PD, dramatic reduction of NADPH levels diminishes the antioxidant capacity of RBCs increasing ROS-induced hemolysis. In PKD, diminished ATP levels affect the functioning of membrane proteins such as Na+/K+ pump or PMCA pump, which will indirectly induce water efflux and RBC dehydration, incrementing RBC fragility and hemolysis.

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Grants and funding

This research was funded by CSIC I+D (2020-557), Universidad de la República, Uruguay to M.N.M., Fondo María Viñas (2019-155597), Agencia Nacional de Investigación e Innovación (ANII), Uruguay to L.T. FO y ACL received scholarships from Comisión Académica de Posgrados, Universidad de la República, Uruguay.