8-hydroxy-2--deoxyguanosine and Pre-Eclampsia

Pregnancy complications including pre-eclampsia, gestational-diabetes mellitus, preterm birth and intrauterine growth restriction can cause acute and chronic health problems for the mother and lead to fetal loss or dysregulation of infant physiology. The human placenta is susceptible to oxidative stress and oxidative damage in early gestation contributes to the onset of these conditions later in pregnancy. Current methods of predicting pregnancy complications are limited and although a large number of factors are associated with disease progression, few biomarkers have been used to aid in disease diagnosis early in gestation. This review discusses the detection of oxidative stress markers in biological fluids and highlights the need for further studies to validate their use in the prediction or diagnosis of pregnancy disorders.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Biomarkers; Deoxyguanosine; Diabetes, Gestational; Female; Fetal Growth Retardation; Glycation End Products, Advanced; Humans; Lipoproteins, LDL; Oxidative Stress; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Protein Carbonylation; Tyrosine

To determine the levels of 8-hydroxydeoxyguanosine (8-OHdG) in preeclampsia (PE) using (enzyme-linked immunosorbent assay (ELISA) method.. Twenty-two pregnant women with severe PE, 18 pregnant women with mild PE, and 40 healthy pregnant women, all between 25 and 41 weeks of gestation, were enrolled in this prospective controlled study. 8-OHdG levels in maternal serum were measured using ELISA method.. The authors observed no statistically significant difference in 8-OHdG levels between the mild-severe PE and control groups (p = 0.208).. The present results do not support the concept that 8-OHdG has a role in the etiopathogenesis of PE.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Deoxyguanosine; Enzyme-Linked Immunosorbent Assay; Female; Gestational Age; Humans; Pre-Eclampsia; Pregnancy; Prospective Studies; Severity of Illness Index; Statistics as Topic

Preeclampsia is a prevalent and enigmatic disease, in part characterized by poor remodeling of the spiral arteries. However, preeclampsia does not always clinically present when remodeling has failed to occur. Hypotheses surrounding the "second hit" that is necessary for the clinical presentation of the disease focus on maternal inflammation and oxidative stress. Yet, the studies to date that have investigated these factors have used cross-sectional study designs or small study populations.. In the present study, we sought to explore longitudinal trajectories, beginning early in gestation, of a panel of inflammation and oxidative stress markers in women who went on to have preeclamptic or normotensive pregnancies.. We examined 441 subjects from the ongoing LIFECODES prospective birth cohort, which included 50 mothers who experienced preeclampsia and 391 mothers with normotensive pregnancies. Participants provided urine and plasma samples at 4 time points during gestation (median, 10, 18, 26, and 35 weeks) that were analyzed for a panel of oxidative stress and inflammation markers. Oxidative stress biomarkers included 8-isoprostane and 8-hydroxydeoxyguanosine. Inflammation biomarkers included C-reactive protein, the cytokines interleukin-1β, -6, and -10, and tumor necrosis factor-α. We created Cox proportional hazard models to calculate hazard ratios based on time of preeclampsia diagnosis in association with biomarker concentrations at each of the 4 study visits.. In adjusted models, hazard ratios of preeclampsia were significantly (P<.01) elevated in association with all inflammation biomarkers that were measured at visit 2 (median, 18 weeks; hazard ratios, 1.31-1.83, in association with an interquartile range increase in biomarker). Hazard ratios at this time point were the most elevated for C-reactive protein, for interleukin-1β, -6, and -10, and for the oxidative stress biomarker 8-isoprostane (hazard ratio, 1.68; 95% confidence interval, 1.14-2.48) compared to other time points. Hazard ratios for tumor necrosis factor-α were consistently elevated at all 4 of the study visits (hazard ratios, 1.49-1.63; P<.01). In sensitivity analyses, we observed that these associations were attenuated within groups typically at higher risk of experiencing preeclampsia, which include African American mothers, mothers with higher body mass index at the beginning of gestation, and pregnancies that ended preterm.. This study provides the most robust data to date on repeated measures of inflammation and oxidative stress in preeclamptic compared with normotensive pregnancies. Within these groups, inflammation and oxidative stress biomarkers show different patterns across gestation, beginning as early as 10 weeks. The start of the second trimester appears to be a particularly important time point for the measurement of these biomarkers. Although biomarkers alone do not appear to be useful in the prediction of preeclampsia, these data are useful in understanding the maternal inflammatory profile in pregnancy before the development of the disease and may be used to further develop an understanding of potentially preventative measures.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Biomarkers; C-Reactive Protein; Cohort Studies; Cytokines; Deoxyguanosine; Dinoprost; Female; Humans; Inflammation; Oxidative Stress; Pre-Eclampsia; Pregnancy; Proportional Hazards Models

To investigate the relation between the severity of hypoxic changes and oxidative DNA damage in the placenta of early and late-onset preeclampic women and fetal growth restriction (FGR), serum parameters of oxidative stress, placental hypoxic change, and oxidative DNA damage were determined.. We examined 10 participants with uncomplicated pregnancies, 13 with early-onset and 12 with late-onset preeclampsia. Maternal and umbilical plasma derivatives of reactive oxygen metabolites (d-ROMs) were measured as markers of oxygen free radicals. Immunohistochemical analysis was performed to measure the proportion of placental trophoblast cell nuclei staining positive for 8-hydroxy-2'-deoxyguanosine (8-OHdG), redox factor-1 (ref-1), and hypoxia-induced factor-1α (HIF-1α), which are markers of oxidative DNA damage, repair functions, and hypoxia status, respectively.. 8-OHdG was higher in both preeclamptic groups, but significantly higher in the early-onset preeclamptic group. Ref-1 was higher in the late-onset preeclamptic group. HIF-1α was higher in both preeclamptic groups, with a tendency towards a higher in the early-onset preeclamptic group.. Our findings indicate that the severity of hypoxic changes and oxidative DNA damage are greater in the placenta of women with early-onset preeclampsia, and that the prolonged preeclamptic conditions may reduce placental blood flow, ultimately leading to FGR.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Cell Hypoxia; Deoxyguanosine; DNA Damage; DNA-(Apurinic or Apyrimidinic Site) Lyase; Female; Fetal Growth Retardation; Gestational Age; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Immunohistochemistry; Oxidation-Reduction; Oxidative Stress; Placenta; Pre-Eclampsia; Pregnancy; Reactive Oxygen Species; Umbilical Arteries

To investigate the association between maternal oxidative stress at mid-gestation and subsequent development of pregnancy complications.. A total of 503 healthy pregnant women provided their blood and urine samples at 24 to 26 weeks of gestation and were prospectively followed through postpartum. These samples were used to assess a variety of oxidative stress markers, including plasma total antioxidant capacity, 8-isoprostane, erythrocyte glutathione peroxidase and superoxide dismutase activity, and urinary 8-hydroxydeoxyguanosine (8-OHdG).. Compared with women with uncomplicated pregnancies, significantly higher plasma 8-isoprostane levels were noted in women who developed preeclampsia (P = .008) and small-for-gestational age infants (P = .002), while higher urinary 8-OHdG concentrations were noted in women who subsequently had low-birth-weight neonates (<2500 g, P = .043).. Increased maternal oxidative stress at mid-gestation was associated with subsequent pregnancy complications.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Antioxidants; Biomarkers; Deoxyguanosine; Dinoprost; Erythrocytes; Female; Gestational Age; Glutathione Peroxidase; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Small for Gestational Age; Oxidative Stress; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Premature Birth; Prospective Studies; Superoxide Dismutase

Abnormal activation and/or dysfunction of the maternal vascular endothelium have been implicated as a cause of the placental ischemia and oxidative damage associated with pregnancy-induced hypertension (PIH).. To clarify the relationship between systemic oxidative stress and placental damage induced by reactive oxygen species (ROS), we immunostained placentas from 27 PIH pregnancies and 41 normal pregnancies for 8-hydroxy-2-deoxyguanosine (8OHdG).. Positive 8OHdG staining was significantly more frequent in the syncytiotrophoblasts from PIH pregnancies compared to normal pregnancies matched for maternal age/gestational age at delivery. Comparison of 8OHdG positive and negative PIH patients revealed that antenatal serum uric acid (UA) was significantly higher, gestational age at delivery was significantly lower and early onset PIH was more frequent in patients with 8OHdG positive staining in the placenta.. These results suggest that ROS directly injures the placental syncytiotrophoblast in PIH patients and that elevated UA in PIH patients, at least partly, indicates placental damage induced by ROS. Moreover, the role and significance of ROS injury in the placenta may differ between early onset and late-onset type PIH.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Age Factors; Biomarkers; Case-Control Studies; Deoxyguanosine; Endothelium, Vascular; Female; Gestational Age; Humans; Middle Aged; Oxidative Stress; Placenta; Pre-Eclampsia; Pregnancy; Reactive Oxygen Species; Uric Acid

Preeclampsia is frequently accompanied by fetal growth restriction (FGR). Preeclampsia increases oxygen free radical production, and the resulting oxidative stress impairs placental blood flow. To determine whether placental oxidative stress is associated with FGR in preeclamptic women, we evaluated placental oxidative DNA damage and its repair in 13 preeclamptic women with FGR, 10 preeclamptic women without FGR, and 11 healthy pregnant women without complications. We measured maternal and umbilical serum derivatives of reactive oxygen metabolites (d-ROMs), as a marker of oxygen free radicals, and pulsatility index (PI) of uterine and umbilical arteries, and performed an immunohistochemical analysis to measure the proportion of nuclei in the placental trophoblast that stained positive for 8-hydroxy-2'-deoxyguanosin (8-OHdG), an indicator of oxidative DNA damage, and redox factor-1 (ref-1), indicative of the repair function towards oxidative DNA damage. D-ROMs were increased in the maternal blood of both preeclamptic groups (with FGR, 687.3 ± 50.4 CARR U, p < 0.01; without FGR, 750.4 ± 87.2 CARR U, p < 0.001) compared with controls (504.7 ± 25.0 CARR U). In contrast, d-ROM levels in the umbilical artery were elevated in preeclamptic women with FGR (134.9 ± 13.3 CARR U, p < 0.01), but not in preeclamptic women without FGR (44.0 ± 7.3 CARR U) compared with controls (38.2 ± 5.0 CARR U). Mean PI for uterine arteries was significantly increased in both preeclamptic groups, and the PI in preeclamptic women with FGR was significantly greater than that in women without FGR (0.94 ± 0.07 vs. 1.31 ± 0.07, p < 0.001). The PI for umbilical arteries was significantly increased in preeclamptic women with FGR (0.90 ± 0.05vs. 1.19 ± 0.07, p < 0.001), but not in preeclamptic women without FGR. The proportion of nuclei positive for 8-OHdG was higher in both groups of preeclamptic women than in the control group, but was higher in preeclamptic women with FGR (0.21 ± 0.05 vs. 0.87 ± 0.01, p < 0.001). The proportion of nuclei positive for ref-1 was higher in preeclamptic women without FGR (0.54 ± 0.06, p < 0.001) than in the control group, whereas the proportion did not differ significantly between normal and preeclamptic women with FGR. Our findings indicate that increased oxidative stress and disrupted compensatory reaction against placental oxidative DNA damage may be associated with FGR in preeclamptic women.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Case-Control Studies; Deoxyguanosine; DNA Damage; DNA-(Apurinic or Apyrimidinic Site) Lyase; Female; Fetal Blood; Fetal Growth Retardation; Free Radicals; Humans; Oxidative Stress; Oxygen; Placenta; Pre-Eclampsia; Pregnancy

Indoleamine 2,3-dioxygenase (IDO) is the rate limiting enzyme of the kynurenine pathway that degrades L-tryptophan, but a wider range of functions have now been proposed for this enzyme, including antioxidant activity. Our previous study revealed that reduced IDO expression in the placenta induces defective feto-maternal immuno-tolerance leading to the onset of pre-eclampsia. In our present study, we assessed the effects of low placental IDO activity as an antioxidant. The placental levels of 8-hydroxy-2'-deoxy-guanosine (8-OHdG), a maker for oxidative damage to DNA, were significantly higher in pre-eclamptic than normotensive pregnancies (P<0.05). Immunohistochemical signals of 8-OHdG were detected mainly in syncytiotrophoblasts and vascular endothelial cells, and co-localized with those for IDO. Furthermore, a significant inverse correlation was found between the IDO activity and 8-OhdG levels. These results show that oxidative stress is associated with decreased IDO activity in the pre-eclamptic placenta and suggest an impact of low IDO activity other than immune modulation in promoting the onset of this disorder.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Antioxidants; Deoxyguanosine; Female; Humans; Indoleamine-Pyrrole 2,3,-Dioxygenase; Oxidative Stress; Placenta; Pre-Eclampsia; Pregnancy; Trophoblasts

Topics: 8-Hydroxy-2'-Deoxyguanosine; Antioxidants; Deoxyguanosine; Female; Humans; Indoleamine-Pyrrole 2,3,-Dioxygenase; Oxidative Stress; Placenta; Pre-Eclampsia; Pregnancy

The objectives of this study were to determine whether oxidative stress early in pregnancy influenced pregnancy outcome. A combination of assays were used for exogenous and endogenous anti-oxidants together with two well accepted biomarkers for oxidative stress, the urinary excretion of 8-iso-PGF(2alpha) (a biomarker marker for lipid oxidation, n=508) and 8-oxo-7,8 dihydro-2 deoxyguanosine (8-OHdG, a biomarker for DNA oxidation, n=487). The two biomarkers tracked different pregnancy outcomes. Isoprostanes were associated with an increased risk of pre-eclampsia and a decreased proportion of female births. In contrast, 8-OHdG tracked lower infant birthweight and shortened gestation duration. Birth defects were associated with low levels of 8-OHdG.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Antioxidants; Biomarkers; Birth Weight; Congenital Abnormalities; Deoxyguanosine; Dinoprost; DNA Damage; Female; Gestational Age; Humans; Infant, Newborn; Lipid Peroxidation; Male; Middle Aged; Oxidants; Oxidative Stress; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Premature Birth; Prospective Studies; Young Adult

Recent evidence suggests that oxidative stress is involved in the pathophysiology of preeclampsia. Using immunohistochemistry and Western blotting, we investigated the oxidative stress- and redox-related molecules, such as 8-hydroxy-2'-deoxyguanosine (8-OHdG), 4-hydroxynonenal (4-HNE), thioredoxin (TRX) and redox factor-1 (ref-1) in the placenta in preeclampsia, intrauterine growth restriction (IUGR), preeclampsia + IUGR and in normal pregnancy. Using immunohistochemistry, the level of 8-OHdG was significantly higher in IUGR ( P=0.012) or preeclampsia + IUGR (P=0.0021) than in normal pregnancy, while TRX expression was significantly higher in preeclampsia (P=0.045), and ref-1 expression was significantly higher in preeclampsia (P=0.017), IUGR (P=0.016) and preeclampsia + IUGR (P=0.0038) than in normal pregnancy. The levels of 4-HNE did not differ significantly between either preeclampsia or IUGR and normal pregnancy. A significant positive correlation was observed between TRX and ref-1 expressions in both normal (rho=0.52) and complicated (rho=0.43) pregnancies. Using Western blotting, ref-1 expression tended to be higher in complicated pregnancies than in normal pregnancy (P=0.09). These results suggest that oxidative DNA damage is increased in IUGR and that redox function is enhanced in both preeclampsia and IUGR compared with normal pregnancy.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aldehydes; Blotting, Western; Deoxyguanosine; DNA Damage; DNA-(Apurinic or Apyrimidinic Site) Lyase; Female; Fetal Growth Retardation; Gestational Age; Humans; Immunohistochemistry; Oxidation-Reduction; Oxidative Stress; Placenta; Pre-Eclampsia; Pregnancy; Thioredoxins

Placental oxidative stress was suggested to play a role in the pathogenesis of pre-eclampsia (PE). In this study, levels of 8-hydroxy-2'-deoxyguanosine (8-OH-dG), a well-established marker of oxidative DNA damage, were analysed in placental cellular DNA from normal (group NP) and pre-eclamptic (group PE) pregnancies as well as from PE pregnancies complicated by intrauterine growth restriction (group PE-IUGR). Placental samples obtained immediately after delivery were frozen at -80 degrees C until analysis. Cellular DNA was isolated, hydrolysed and analysed using high-performance liquid chromatography. Native nucleosides were monitored at 254 nm and 8-OH-dG using electrochemical detection. Concentrations of 8-OH-dG were expressed as micro mol/mol 2'-deoxyguanosine. In group NP, mean concentration of 8-OH-dG reached 179.97+/-80.58 (+/-SEM; micro mol/mol dG). 8-OH-dG levels were higher in group PE (273.44+/-110.14 micro mol/mol), but the difference was not significant in comparison with group NP. Highest concentrations of 8-OH-dG were found in group PE-IUGR (428.97+/-141.40 micro mol/mol), with levels significantly higher than in group NP, but not group PE. The results indicate a positive correlation between the severity of PE and the degree of oxidative stress and corroborate previous studies suggesting reactive oxygen species to be involved in the pathophysiology of PE.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Deoxyguanosine; DNA Damage; Female; Fetal Growth Retardation; Humans; Infant, Newborn; Oxidation-Reduction; Oxidative Stress; Placenta; Pre-Eclampsia; Pregnancy