Introduction-
Oxidative stress is a pathological condition characterized by an excess of oxidant products, namely free radicals, which are not adequately counteracted by antioxidant systems. In neonatal erythrocytes, free-radical mediated-oxidative stress leads to eryptosis, a suicidal death process of erythrocytes consequent to alteration of cell integrity. Neonatal red blood cells are targets as well as generators of free radicals through the Fenton and Haber-Weiss reactions.
Fig 1- Fenton and Haber-Weiss Reactions
Enhanced eryptosis in case of oxidative stress damage results in anemia if the increased loss of erythrocytes is not enough to compensate for by enhanced new erythrocyte synthesis. The oxidative disruption of the red cells may cause unconjugated idiopathic hyperbilirubinemia in neonates.
Research-
Oxidative stress in the newborn
Oxidative stress is the consequence of an imbalance between oxidant products and antioxidant systems. When free radicals react with other radicals, the unpaired electrons form a covalent bond. The resulting molecules may give rise to toxic products. Antioxidants (for example, vitamins C and E, glutathione (GSH), catalase, etc.) are able to neutralize free radicals, thus protecting from oxidative stress tissue damage.[3] The sudden increase in oxygen concentration at birth leads to an increase in free radical production, both in term and preterm babies, who are unable to counteract this burden. Premature babies are particularly vulnerable to oxidative stress damage due to the scarce antioxidant capacity, mainly produced during the latter part of gestation, along with the immaturity of the antioxidant production system.
Eryptosis: The suicidal death of neonatal erythrocytes
The erythrocyte is a highly specialized cell with a limited metabolic repertoire. Eryptosis is a coordinated, programmed cell death that allows to eliminate defective erythrocytes. Xenobiotics, osmotic shock, oxidative stress, and sudden changes in temperature activate the kinase cascade that leads to cell death. Neonatal erythrocytes seem to target as well as, generate simultaneously free radicals through the Fenton reaction. Oxidative stress induces the oxidation of oxyhemoglobin to methemoglobin; hemoglobin degradation with iron release induces the Fenton reaction, which generates the superoxide anion radical. Free radicals cause the denaturation of membrane proteins with consequent lipid peroxidation.
Oxidative stress in neonatal idiopathic hyperbilirubinemia
The role of increased hemolysis in the development of neonatal jaundice of unknown etiology has long been studied. The oxidative disruption of the red cells may cause unconjugated idiopathic hyperbilirubinemia in neonates. It has been observed that erythrocyte antioxidant enzymes are depleted in infants who develop idiopathic unconjugated hyperbilirubinemia, due to the harmful effect of the circulating oxidants, as a result of the inability of the adequate antioxidant system to counterbalance these.
Conclusion-
The oxidative disruption of the red cells causes unconjugated idiopathic hyperbilirubinemia in neonates. The eryptosis may be enhanced by the increased number of erythrocytes at birth following delayed cord clamping (DCC). Protecting newborns from oxidative stress at birth might reduce this, thereby reducing the risk of anemia in very low gestational age infants or hyperbilirubinemia in term newborns subjected to DCC.
Reference-
Serafina Perrone, Chiara Lembo, Maurizio Giordano, Chiara Petrolini, Laura Cannavò, Eloisa Gitto, Molecular mechanisms of oxidative stress‐related neonatal jaundice.
Journal of Biochemical and Molecular Toxicology,
Volume 37, Issue 6,
Image reference (Fig. 1)-https://www.researchgate.net/publication/263708888/figure/fig1/AS:1088655665954892@1636567145490/Fenton-and-Haber-Weiss-reaction-Reduced-form-of-transition-metals-M-n-reacts-trough.jpg
By Debangana Banerjee
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