A Study of Oxidative DNA Damage, Lipid Oxidation and Antioxidant Activity in Neonates with Respiratory Distress Syndrome

Abstract

SUMMARY R espiratory distress syndrome is an acute lung disease of premature infant caused by inadequate amounts of surfactant. Decreased surfactant results in insufficient surface tension in the alveolus during expiration, leading to atelectasis, decreased gas exchange, severe hypoxia and acidosis. Oxidative stress occurs as a result of increased activity of free radical–producing enzymes, decreased activity of free radical–removing enzymes, and insufficient levels of antioxidants. Preterm neonates suffer RDS due to the rapid formation of the oxygen reactive species, which surpasses the detoxification capacity of anti-oxidative defense system. The high chemical reactivity of free radical leads to damage to a variety of cellular macro molecules including proteins. The aim of study was to evaluate oxidant-antioxidant balance in preterm neonates with RDS by measuring total antioxidant capacity and malondialdehyde as well as the novel marker for oxidative DNA damage “8-Hydroxy-desoxyguanosine (8-OHdG)” in day 1 and day 3 of life. This study comprised 80 preterm neonates less than 34 weeks of gestational age, admitted at Neonatal Intensive Care Unit, Ain Shams University Hospitals. They were 40 preterm neonates with RDS and 40 preterm neonates without RDS. All newborns were subjected to detailed medical history, thorough clinical examination. The degree of respiratory distress was assessed according to Down score. Respiratory distress grade was determined according to chest X ray. Laboratory investigations included complete blood count, random blood sugar, arterial blood gases, total antioxidant capacity, malondialdehyde as an index of lipid peroxiadation, 8-OHdG levels by ELISA and trace elements (copper, zinc, calcium, magnesium and iron). Neonates with RDS had lower birth weight and gestational age in comparison to control group. There was no significant difference in maternal age, parity, mode of delivery, PROM and maternal disease between mothers of neonates with RDS and control group. Antenatal steroid intake was comparable in both groups. In our study, comparison of hematological and biochemical data between neonates with RDS at day 1 and control group revealed no significant difference. As regards oxidative stress markers, we found that day 1 TAC, MDA and 8-OHG were significantly high compared with control group. No significant difference was found as regard trace elements (zinc, calcium, magnesium, iron) except for copper which was significantly lower in neonates with RDS. Additionally, comparison between levels oxidative stress markers at day 1 and day 3 showed that TAC was significantly lower among neonates with RDS at day 3 compared with day 1 while MDA and 8-OHdG were significantly higher at day 3. Analysis of 8-OHdG levels in relation to maternal clinical characteristics of neonates with RDS revealed no significant difference. As regards neonatal data, 8-OHdG levels at day 1 and day 3 were significantly higher in neonates in RD grade 3-4 compared with those in grades 2. Moreover, day 1 and day 3 8-OHdG levels were significantly increased among patients on mechanical ventilation. 8-OHdG levels at day 3 were also significant in relation to mortality rate being higher in those who died. Correlation studies revealed that 8-OHdG levels at days 1 and 3 are negatively correlated to gestational age, birth weight, OFC and PH. There was significant positive correlation with each of maternal age, duration of ventilation and duration of hospitalization as well as MDA and CO2 while no significant correlations were found with levels of the studied trace elements. As regards the correlations between TAC and MDA levels at day 1 and the studied laboratory parameters, positive correlations were found between TAC and copper as well as zinc levels which are powerful antioxidants.