Formation and Detection of Highly Oxidized Hemoglobin Forms in Biological Fluids during Hemolytic Conditions.

Benard Bogonko Nyakundi,Béla Nagy,Andrea Nagy,László Novák,Viktória Jeney,Judit Erdei,László Bognár,János Kappelmayer,György Paragh,Andrea Tóth,Enikő Balogh

doi:10.1155/2020/8929020

Benard Bogonko Nyakundi, Béla Nagy + Show 9 more

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https://doi.org/10.1155/2020/8929020

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Abstract

Hemolytic diseases are characterized by an accelerated breakdown of red blood cells (RBCs) and the release of hemoglobin (Hb). Following, RBC lysis Hb oxidation occurs with the formation of different redox states of Hb (metHb and ferrylHb) and the release of heme. ferrylHb is unstable and decomposes to metHb with the concomitant formation of globin radicals and eventually covalently crosslinked Hb multimers. The goal of the present study was to determine the concentrations of the different redox states of Hb in biological samples during hemolytic conditions. We used plasma and urine samples of mice with intravascular hemolysis and human cerebrospinal fluid (CSF) samples following intraventricular hemorrhage. Because ferrylHb is highly unstable, we also addressed the fate of this species. metHb and free heme time-dependently accumulate in plasma and CSF samples following intravascular hemolysis and intraventricular hemorrhage, respectively. ferrylHb is hardly detectable in the biological samples during hemolytic conditions. Under in vitro conditions, ferrylHb decomposes quickly to metHb, which process is associated with the formation of covalently crosslinked Hb multimers. We detected these covalently crosslinked Hb multimers in plasma, urine, and CSF samples during hemolytic conditions. Because globin modification is specific for these Hb forms, we propose to call this heterogeneous form of Hb produced during ferrylHb decomposition as globin-modified oxidized Hb (gmoxHb). Understanding the formation and the contribution of gmoxHb species to the pathogenesis of hemolytic conditions could have therapeutic implications in the treatment of hemolytic diseases.

Highlights

The average life span of red blood cells (RBCs) in the circulation is about 120 days
Intravascular Hemolysis and intraventricular hemorrhage (IVH) Are Associated with the Formation of Hb Forms with Different Oxidation Status
To see whether Hb oxidation occurs in cerebrospinal fluid (CSF), we used the leftover of CSF samples taken for diagnostic purposes from preterm infants with IVH

Summary

Introduction

The average life span of red blood cells (RBCs) in the circulation is about 120 days. Earlier destruction of RBCs is defined as hemolysis which can occur in the vasculature or in the extravascular space. Diverse conditions can trigger hemolysis including intrinsic RBC defects such as hemoglobinopathies, RBC enzyme deficiencies and RBC membrane disorders, as well as extrinsic RBC defects triggered by auto- and alloimmune reactions, oxidants, toxins, infections, and mechanical stress (reviewed in [1, 2]). RBC content is released into the plasma or the extravascular environment. Outside of Oxidative Medicine and Cellular Longevity the protective environment of RBCs Hb is prone to oxidation (reviewed in [3])

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