3-nitrotyrosine and Diabetes--Gestational

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 evaluate serum concentration of 8-isoprostane, nitrotyrosine (NT), and total antioxidant capacity (TAC) in pregnant women with diabetes mellitus (DM) considering preconception planning and method of diabetes correction in 11-14 and 30-34 weeks.. The study included 130 women: T1DM (n = 40), T2DM (n = 35), gestational diabetes (GDM, n = 40) and the control group (n = 15). The serum concentrations of NT, 8-isoprostane, and TAC were measured by ELISA methods.. Elevated 8-isoprostane levels were observed in all patients with DM, but this biomarker's maximum values have been seen in T1DM and T2DM on insulin groups. A similar tendency was observed for the concentration of NT in both the 1st and 3rd trimesters. TAC levels showed a statistically relevant decrease in all DM groups compared to the control. The correlation analysis showed a direct correlation between HbA1c and serum 8-isoprostane levels in the 1st (r = .27) and 3rd (r = .3) pregnancy trimesters as well as inverse correlation with TAC level (r = -.48). Direct (NT, 8-isoprostane) and inverse correlations (TAC) were fixated for this biomarker concentration and preeclampsia rates.. DM in pregnancy is related to oxidative stress activation, which might lead to the development of adverse perinatal outcomes.

Topics: Adult; Antioxidants; Case-Control Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetes, Gestational; Dinoprost; Female; Humans; Pre-Eclampsia; Pregnancy; Pregnancy in Diabetics; Pregnancy Outcome; Russia; Tyrosine

Gestational diabetes (GDM) is associated with increased oxidative stress and overexpression of inflammatory cytokines, both of which might lead to endothelial dysfunction and vascular disease. As such, GDM could be viewed as a sort of ‘short lived’ metabolic syndrome. As umbilical cord vessels represent a suitable model for the study of vascular alterations brought about by GDM, the aim of the present work was to characterize the phenotype of human umbilical vein endothelial cells (HUVECs) chronically exposed to hyperglycaemia and to a pro-inflammatory environment during pregnancy so as to identify molecular modifications of cellular homoeostasis eventually impacting on endothelial dysfunction.. Tissue specimens and HUVECs were obtained from umbilical cords of GDMand control women. As compared to controls, GD-HUVEC exhibited enhanced monocyte adhesion and vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1(ICAM-1) expression and exposure on plasma membrane after tumour necrosis factor-alpha(TNF-α) stimulation (Western blot, flow cytometer). As compared to control cells, GD-HUVEC in basal conditions exhibited enhanced monocyte adhesion, nitric oxide synthase (NOS) expression and activity (eNOS Real-Time polymerase chain reaction, Western Blot for eNOS total protein and monomers/dimers ratio, conversion of [3H]-L-arginine in [3H]-L-citrulline), increased O(-)(2)egeneration together with increased NT levels (immunofluorescence) and reduced NO bioavailability(guanosine 3',5'-monophosphate (cGMP) production, EIA). Furthermore, immunohistochemistry revealed increased eNOS and NT immunoreactivity in GD umbilical cords.. Endothelial cells exposed in vivo even transiently to hyperglycaemia, oxidative stress and inflammation exhibit durable pro-atherogenic modifications.

Topics: Adult; Atherosclerosis; Blood Glucose; Cell Adhesion; Cyclic AMP; Diabetes, Gestational; Female; Glucose Tolerance Test; Homeostasis; Human Umbilical Vein Endothelial Cells; Humans; Hyperglycemia; Leukocytes; Nitric Oxide; Nitric Oxide Synthase Type III; Oxidative Stress; Pregnancy; Tyrosine; Umbilical Cord; Vascular Diseases

In spite of improvement in obstetrical care, pregnancy in women with type 1 diabetes mellitus is associated with increased perinatal morbidity and mortality. Hyperglycemia during pregnancy causes excessive fetal growth and chronic fetal hypoxia as reflected in increased erythropoietin (EPO) levels in amniotic fluid (AF).. We hypothesized that the degree of fetal hypoxia would correlate with fetal oxidative and nitrosative stress as evidenced ty the concentration of specific biomarkers in AF.. 19 pregnant women with type 1 or insulin-treated gestational diabetes mellitus were studied. AF samples were collected and processed for EPO, meta-tyrosine, nitro-tyrosine and 8-hydroxy-2-deoxiguanosine by chemiluminescent immunoassay and high-performance liquid chromatography coupled to tandem mass spectrometry methods, respectively.. The mean (SD) of the last HbA1c concentration before delivery was 7.7% (1.1). Median gestational age was 258 days (range 231-268). Birth weight was 3,868 ± 695 g with a z-score >2 SD in 47% of the cases. A significant correlation was found between the concentrations of AF EPO and meta-tyrosine/phenylalanine ratio (p < 0.001), nitro-tyrosine (p < 0.01) and 8-oxo-dG/2dG ratio (p < 0.001).. We confirmed that fetuses of type 1 diabetes or insulin-treated gestational diabetes pregnancies experience chronic hypoxia as reflected by increased EPO concentrations in AF near term. Moreover, EPO levels significantly correlated with the concentration of oxidative and nitrosative stress biomarkers in AF. This pro-oxidant status may predispose newborn infants to poor postnatal adaptation and early neonatal complications.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Amniocentesis; Amniotic Fluid; Biomarkers; Birth Weight; Chromatography, High Pressure Liquid; Chronic Disease; Deoxyguanosine; Diabetes Mellitus, Type 1; Diabetes, Gestational; Erythropoietin; Female; Fetal Hypoxia; Gestational Age; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Immunoassay; Infant, Newborn; Insulin; Male; Nitrosation; Oxidative Stress; Pilot Projects; Pregnancy; Pregnancy in Diabetics; Tandem Mass Spectrometry; Tyrosine; Young Adult