Antioxidant enzyme activities are decreased in preterm infants and in neonates born via caesarean section

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Abstract

Objectives: To investigate the antioxidant defense potential of human neonates according to gestational age and mode of delivery. Study design: Four study groups were established, full-term normal spontaneous vaginal delivery (FT-NSVD, n=24), full-term caesarean section (FT-CS, n=19), preterm normal spontaneous vaginal delivery (PT-NSVD, n=15) preterm caesarean section (PT-CS, n=21). The activity of catalase (CAT), glutathion peroxidase (GPX), Cu/Zn superoxide dismutase (Cu/Zn-SOD) were determined from cord blood. Statistical analysis was made by ANOVA. Results: CAT activity was significantly higher in full-term than in preterm newborns. In both the categories, neonates born via caesarean section had significantly lower CAT activities. GPX activity was significantly higher in the FT-NSVD group than in any other group. Cu/Zn-SOD activity was significantly higher in full-term neonates than in preterms and no difference was found related to the mode of delivery. Conclusions: Prematurity and caesarean section may cause a deficiency of antioxidant defense in human newborn.

Introduction

Aerobic organisms possess antioxidant defense systems that deal with reactive oxygen species (ROS) as a result of aerobic respiration and substrate oxidation. ROS, including hydroxil radicals (radical dotOH), superoxide anions (O2radical dot) and hydrogen peroxide (H2O2), are generated in response to external and internal stimuli [1], [2], [3]. Low levels of ROS are necessary for several biological processes including intracellular differentiation and cell progression or arrest of growth, apoptosis, immunity and defense against microorganisms [4]. In contrast, high doses and/or inadequate removal of ROS result in oxidative stress, which may cause damages to biological macromolecules. The naturally occurring antioxidants in low-density lipoproteins (LDLs) and plasma protect cells from oxidation. The prevention of lipid peroxidation is an essential process because lipid peroxidation products can cause DNA damage and directly inhibit proteins, such as Na+/K+-ATPases and glutamate transporters [5].

The enzymatic antioxidant defenses include superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase (CAT). Superoxide dismutase (EC1.15.1.1) is the antioxidant enzyme that catalyses the dismutation of the highly reactive superoxide anion to O2 and H2O2. In humans, there are three forms of SOD: cytosolic Cu/Zn-SOD, mitochondrial Mn-SOD and extracellular SOD. Cu/Zn-SOD is believed to play a major role in the first line of antioxidant defense and high SOD activities were correlated with high immune competence [6]. CAT and GPX play an important role in the detoxification of H2O2. CAT (EC1.11.1.6) reacts very efficiently with H2O2 to form water and molecular oxygen and with hydrogen donors with peroxidase activity, thus protecting cells against the H2O2 generated within them. GPX (EC1.11.1.19) catalyses the reaction of hydroperoxides using GSH, protecting mammalian cells against oxidative damage. In fact, glutathione metabolism is one of the most essential antioxidative defense mechanisms [7].

The onset of labor is associated with an increased production of proinflammatory mediators, which might induce an increase in the production of free radicals. In addition, oxygenation of both mother and child tissues oscillate frequently during labor, leading to an overproduction of free radicals as a consequence of tissue reoxigenation, which suggests that both maternal and fetal antioxidant systems might be overloaded during vaginal delivery [8]. This hypothesis is supported by several findings, including those which indicate that xanthine oxidase activity in placentae of laboring women was higher than in placentae obtained from pregnancies terminated by caesarean section. These data further indicate that labor might enhance free radical production [9]. However, the competence of enzymatic antioxidant systems through which the newborn might protect himself against an increased load of free radicals during labor depends on the gestational age, since antioxidant enzymes display lower activities during intrauterine life and in preterm than in full-term neonates [10], [11], [12]. Therefore, in the present study we proposed to elucidate the antioxidative enzyme activity in full-term and preterm neonates and the correlation between the way of delivery (per vias naturales versus caesarean section) and the antioxidant defense systems of the newborn.

Section snippets

Patients

The study was previously approved by the Human Investigation Review Board, and blood samples were collected after informed consent had been obtained. According to the mode of delivery and gestational age, four study groups were established: full-term normal spontaneous vaginal delivery (FT-NSVD, n=24), full-term caesarean section (FT-CS, n=19), preterm normal spontaneous vaginal delivery (PT-NSVD, n=15) and preterm caesarean section (PT-CS, n=21). In both the full-term and preterm categories,

Results

CAT activity in healthy neonates proved to be significantly higher in the FT-NSVD category in comparison to PT-NSVD (average±S.E. was 2.10±0.16 mBU/mg protein for full-term healthy neonates and 1.86±0.16 mBU/mg protein for the preterm healthy neonatal population). We found that the neonates born via cesarean section had a significantly lower CAT activity than the vaginally delivered babies in both the full-term and the preterm category (Fig. 1A).

GPX activity showed to be significantly higher in

Discussion

Oxygen species are important participants in damage caused by virus infections, progression to cancer and neurodegenerative processes [18]. They can be toxic at the molecular level and they are important effectors in aging and life-span determination. Our study raised the question of possible correlation between the antioxidant defense of the neonate and the way of delivery. This has been hypothesized by several recent findings, especially those, which are indicating an increase in free radical

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