DNA damage and oxidative stress in patients with mild preeclampsia and offspring

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Abstract

Objective

Oxidative stress has been shown to play an important role in the pathogenesis of pre-eclampsia, and DNA damage frequently occurs in cells exposed to such stress. The aim of the present study was to investigate DNA damage and oxidative stress in mildly pre-eclamptic women and their offspring.

Study design

We studied 25 mildly pre-eclamptic mothers, 20 healthy controls, and their infants. Mononuclear leukocyte DNA damage, total antioxidant status (TAS), and total oxidant status (TOS) were determined and the oxidative stress index (OSI) was calculated.

Results

DNA damage, and TOS and OSI levels were significantly increased, and TAS levels significantly decreased, in maternal and cord blood samples of the mildly pre-eclamptic group. A positive correlation between the extent of DNA damage and diastolic blood pressure was evident in pre-eclamptic mothers and there was a negative correlation between the extent of DNA damage and TOS.

Conclusion

Both oxidative stress and DNA damage are elevated in mildly pre-eclamptic patients and their offspring. Increased oxidative stress may be important in inducing DNA damage in pre-eclamptic patients.

Introduction

Pre-eclampsia is a complex multisystemic disorder and is associated with the highest maternal and fetal morbidity and mortality of all pregnancy complications [1]. It is recognized that injury to the vascular endothelium is a basic pathological event in pre-eclampsia [2] and such endothelial damage is mediated by oxidative stress imposed by increased generation of oxygen free radicals or a fall in antioxidant levels [3]. Patients with pre-eclampsia have been shown to be under increased oxidative stress [4] and oxygen free radicals created by such stress induce several types of DNA damage [5]. Many pathological conditions including various cancers, cardiovascular and neurodegenerative diseases, inflammation/infection, and aging are associated with DNA damage [6], [7].

Several methods have been employed to monitor genetic damage to mononuclear leukocytes as an indicator of general genetic damage. These include the micronucleus (MN) test, analysis of chromosomal aberrations, the sister-chromatid exchange (SCE) test, gene mutation tests, and the comet assay [8]. Of these tests, the comet assay (single-cell gel electrophoresis) is a well-established genotoxicity test that is simple, rapid and sensitive; the test has been used to assess the extent of endogenous DNA damage [8], [9]. The assay has not been used, however, to gather information on any possible peripheral DNA damage in women with mild pre-eclampsia. In the present study, therefore, we explored DNA damage and oxidative marker levels in mildly pre-eclamptic women and their offspring to determine if DNA damage and oxidant status were associated in women with this syndrome.

Section snippets

Subjects

This cross-sectional study was conducted at the Department of Obstetrics and Gynecology at Harran University School of Medicine and Sanliurfa Women's Health and Maternity Hospital between January 2012 and August 2012. Twenty-five hypertensive pregnant women (mildly pre-eclamptic) and 20 normotensive pregnant women were included. Mild pre-eclampsia was considered present when a diastolic blood pressure of 90 mm Hg or greater was measured on two occasions at least 6 h apart and when proteinuria was

Results

The demographic and clinical characteristics of the subjects are shown in Table 1. Body mass index (BMI) did not differ significantly between the two groups. Newborns of pre-eclamptic mothers had significantly lower Apgar scores and lower birthweights. Pre-eclamptic mothers’ blood samples had significantly higher levels of aspartate aminotransferase (AST) and creatinine than did control samples and the white blood cell (WBC) count was also higher (Table 2). The extent of damage to mononuclear

Comment

We found that women whose pregnancies were complicated by mild pre-eclampsia had increased levels of mononuclear DNA damage, TOS, and OSI, and a decreased TAS level compared to woman with normal pregnancies. Additionally, increased levels of umbilical cord mononuclear leukocyte DNA damage, TOS, OSI, and a decreased TAS level were evident in the test group. Moreover, in that group, the extent of DNA damage was negatively correlated with TAS and positively correlated with diastolic blood pressure.

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