Relationship Between Oxidative Stress Markers and Endothelin-1 Levels in Newborns of Different Gestational Ages.

Gospodin Stefanov,Bhagya Puppala,Anil Gulati,Seema Briyal,Gwendolyn Pais

doi:10.3389/fped.2020.00279

Gospodin Stefanov, Bhagya Puppala + Show 3 more

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https://doi.org/10.3389/fped.2020.00279

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Abstract

Oxidative stress results from excessive reactive oxygen species formation and/or inadequate antioxidant defense. Premature and critically ill infants are especially susceptible due to an immature intrinsic antioxidant system that cannot fully compensate for a free radical load. Oxidative stress is also associated with endothelial dysfunction and alterations in Endothelin-1 (ET-1) signaling pathways. However, the effects of the complex interaction between oxidative stress and ET-1 in newborns are not well-understood. The objective of this pilot study was to determine the relationship between levels of common oxidative stress biomarkers [glutathione (GSH), malondialdehyde (MDA)] and ET-1 in newborns of different gestational ages. In a level IV NICU, 63 neonates were prospectively enrolled and divided into groups based on gestational age at birth: Early Preterm (24 0/7–30 6/7 weeks), Late Preterm (31 0/7–36 6/7 weeks), and Term (37 0/7–42 weeks). Umbilical cord (1.5 mL) and 24(±4) h of life (24 h) (1 mL) blood samples were collected for GSH, MDA, and ET-1 analyses. GSH, MDA, and ET-1 were determined using established methodology. Mean cord MDA levels for all age groups, Early Preterm (2.93 ± 0.08 pg/ml), Late Preterm (2.73 ± 0.15 pg/ml), and Term (2.92 ± 0.13 pg/ml), were significantly higher than those at 24 h of life (p < 0.001). Mean cord ET-1 levels were significantly higher than 24 h samples in both Early and Late Preterm groups (p < 0.05). Cord and 24 h ET-1 levels did not correlate with MDA and GSH levels at birth (r2 = 0.03, p > 0.05 and r2 = 0.001, p > 0.05, respectively) or 24 h of life (r2 = 0.001, p > 0.05 and r2 = 0.03, p > 0.05, respectively). Preterm neonates exposed to prenatal corticosteroids (1.87 ± 0.31 pg/ml) had lower cord MDA levels than non-exposed neonates (2.85 ± 0.12 pg/ml) (p < 0.05). Both cord and 24 h OS markers were significantly higher in neonates treated with oxygen therapy (p < 0.005 and p < 0.05, respectively) than those who did not receive supplemental oxygen. Oxidative stress markers (MDA and GSH) and ET-1 levels act independently. MDA is higher in cord blood than at 24 h of life regardless of gestational age. In preterm neonates, ET-1 levels are higher in umbilical cord blood compared to 24 h of life.

Highlights

Redox homeostasis relies on the critical interplay between reactive oxygen species (ROS) production and the ability of the body’s antioxidant defense system to subsequently inactivate it
Mean cord MDA levels for all age groups, Early Preterm (2.93 ± 0.08 nmol/L), Late Preterm (2.73 ± 0.15 nmol/L), and Term (2.92 ± 0.13 nmol/L), were significantly higher than those obtained at 24 h of life (p < 0.001) (Figure 1)
The results of our study demonstrated that ET-1 levels were higher in umbilical cord blood compared to 24 h-oflife samples in both Early and Late preterm groups

Summary

Introduction

Redox homeostasis relies on the critical interplay between reactive oxygen species (ROS) production and the ability of the body’s antioxidant defense system to subsequently inactivate it. Excessive free radicals are neutralized by antioxidants that are either endogenous/enzymatic (e.g., superoxide dismutase, catalase, and glutathione) or exogenous/nonenzymatic (e.g., vitamins A, C, E, and selenium) [2, 3]. Alterations in this fragile balance—known as oxidative stress—are caused by excessive ROS formation, impaired ROS inactivation due to an overwhelmed intrinsic antioxidant defense, or a combination of both. Redox homeostasis is burdened at birth during the transition to extrauterine life which involves a series of physiological changes that significantly increase both ROS production and the potential for OS [6, 7]. ROS have been implicated in the pathogenesis of many neonatal morbidities, such as retinopathy of prematurity, hypoxic-ischemic brain injury, intraventricular hemorrhage, and chronic lung disease [10, 12]

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