Oxidant injury in neonatal erythrocytes during the perinatal period.

Abstract

It has been known for many decades that oxidative stress leads to oxidation of hemoglobin and damage to the erythrocyte membrane. More recently, the factors involved in denaturating of membrane proteins and lipid peroxidation have been investigated in detail, as well as the mechanism of reactive oxygen species formation in red cells. Oxidative stress depletes adenosine triphosphate (ATP) and adenine nucleotides, whereas adenosine monophosphate (AMP) deaminase seems to depress energy metabolism by blocking the salvage pathway of purine nucleotides. Depletion of ATP and activation of AMP deaminase are related to calcium ion concentrations. Denaturating of membrane proteins generally precedes lipid peroxidation and consequent phagocytosis due to caspase activation. Extensive investigations demonstrated the key role of oxidative stress and iron release in a reactive form causing membrane protein damage via the Fenton reaction and hydroxyl radical production. In the absence of efficient protection by antioxidant factors and other molecules such as flavonoids, oxidative stress is responsible for the release of iron in reactive form, predisposing red cells to hemolysis through the formation of senescence antigen. Other well-known sources of oxidative stress in red cells are free radical production outside the red cell by activated phagocytes, endothelial metabolism, hyperoxia, ischemia-reperfusion and the arachidonic acid cascade. The recent insight into the mechanism of oxidative injury of red cells and evidence of relationships between erythrocyte oxidative stress and hypoxia suggest that increased hemolysis is induced by severe hypoxia and acidosis in the fetus as well as the newborn.