Regulation of the Structural Stability of Erythrocytes by Hydrogen Peroxide: Mathematical Model and Experiment

Abstract

In this study, the regulatory mechanisms induced by extracellular hydrogen peroxide were analyzed on the basis of a mathematical model that considers the key stages of the formation of methemoglobin and ferrylhemoglobin, as well as their binding to the erythrocyte membrane. Numerical modeling has shown that reversible binding of methemoglobin to the membrane is an adaptive mechanism aimed at stabilizing the lipid bilayer of the membrane. On the other hand, an increase in the concentration of ferrylhemoglobin and its binding to the membrane leads to an increase in pathophysiological processes that reduce the structural stability of cells. The quantity of methemoglobins and ferrylhemoglobins formed depends on the concentration of extracellular hydrogen peroxide and exposition time, the number of cells in the sample, the state of the antioxidant system of erythrocytes, the metabolic activity of cells and external metabolic conditions. Based on numerical modeling, optimal conditions (oxidant concentration and exposition time) have been determined, under which the activation of adaptive processes occurs. Experiments with erythrocyte hemolysis in vitro have shown that hydrogen peroxide at concentrations of 10-200 μM causes an increase in the structural stability of the membrane and a decrease in the proportion of hemolyzed erythrocytes.

The Protective Effect of Hydrogen Peroxide on Erythrocyte Hemolysis Induced by Silver Nanoparticles

“…We have previously shown that the ratio of membrane complexes of various oxidized forms of hemoglobin determined the hormesis dependence of the response of erythrocytes to the action of hydrogen peroxide; namely, it was regulatory at low concentrations and damaging at high concentrations [14]. The range of hydrogen peroxide concentrations at which an increase in the structural stability of the membrane (the hormesis region) was observed depended on a number of internal and external factors.…”

“…The protective properties of cells during hemolysis are determined by the structural stability of the membrane and are characterized by the protection coefficient k p . Based on previous studies [14], the model assumed that the structural stability of the membrane depended on the number of membrane complexes of methemoglobin and ferryl hemoglobin and changes over time.…”

“…To quantify the dynamics of changes in the protective properties of the cell, the key stages of the formation of methemoglobin and ferrylhemoglobin and their binding to the membrane under the action of extracellular hydrogen peroxide were considered based on the mathematical model described earlier [14]. To consider the influence of silver nanoparticles, a number of changes have been made to the model.…”