Uric acid as a pathogenic factor in preeclampsia

Lab 336A, Magee-Womens Research Institute, 204 Craft Ave, Pittsburgh, PA 15213, USA.
Placenta (Impact Factor: 3.29). 04/2008; 29 Suppl A(suppl A):S67-72. DOI: 10.1016/j.placenta.2007.11.001
Source: PubMed

ABSTRACT Hyperuricemia is a common finding in preeclamptic pregnancies evident from early pregnancy. Despite the fact that elevated uric acid often pre-dates the onset of clinical manifestations of preeclampsia, hyperuricemia is usually considered secondary to altered kidney function. Increased serum uric acid is associated with hypertension, renal disease and adverse cardiovascular events in the non-pregnant population and with adverse fetal outcomes in hypertensive pregnancies. We hypothesize that an elevated concentration of uric acid in preeclamptic women is not simply a marker of disease severity but rather contributes directly to the pathogenesis of the disorder. Using epidemiological and experimental evidence, gained largely outside of pregnancy, we will propose pathogenic roles for uric acid in preeclamptic pregnancies. Uric acid's ability to promote inflammation, oxidative stress and endothelial dysfunction will be highlighted with discussions of the potential impact on placental development and function and maternal vascular health.

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    • "However, low UA levels in plasma and urine associate with worse cognitive performance in PD [11]. UA is a pathogenic factor in pre-eclampsia for pregnant women [12] [13]. It acts as a role of insulin resistance in older [14] and pregnant women [15]. "
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    ABSTRACT: This paper describes the sensitive and selective determination of uric acid (UA) in the presence of important interferences, ascorbic acid (AA), dopamine (DA), tyrosine (Tyr) and methionine (Met) at physiological pH using an electropolymerized film of 3-amino-5-mercapto-1,2,4-triazole on glassy carbon (p-AMTa) electrode. The p-AMTa electrode shows an excellent electrocatalytic activity towards UA. This was understood from the observed higher oxidation current and heterogeneous rate constant (3.24×10(-5)ms(-1)) for UA when compared to bare GC electrode (4.63×10(-6)ms(-1)). The selective determination of UA in the presence of 1000-fold excess of AA was achieved using p-AMTa electrode. Further, the p-AMTa electrode was successfully used for the simultaneous and selective determination of UA in the presence of important interferences, DA, Tyr and Met. Using amperometric method, 40nM UA was detected for the first time. The current response of UA was increased linearly while increasing its concentration from 40nM to 0.1mM and a detection limit was found to be 0.52nM (S/N=3). Finally, the practical application of the present method was demonstrated by determining UA in human urine and blood serum samples.
    Bioelectrochemistry (Amsterdam, Netherlands) 05/2012; 88:22-9. DOI:10.1016/j.bioelechem.2012.05.005 · 3.87 Impact Factor
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    • "Xanthine oxidase conversion of purines is coupled to the generation of • O 2 − . Consequently, elevations in plasma urate have become an established in vivo bioassay for • O 2 − generation (Halliwell & Gutteridge, 1999) and of placental and fetal complications in pregnancy (Roberts et al. 2005; Bainbridge & Roberts, 2008). The sulphur amino acid L-cysteine is involved in the regulation of oxidative status and of protein metabolism. "
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    ABSTRACT: This study isolated the effects of maternal hypoxia independent of changes in maternal nutrition on maternal circulatory and placental molecular indices of oxidative stress and determined whether maternal antioxidant treatment conferred protection. Pregnant rats were subjected to normoxic pregnancy or 13% O2 chronic hypoxia for most of gestation with and without maternal treatment with vitamin C in the drinking water. Maternal hypoxia with and without vitamin C did not affect maternal food or water intake and led to a significant increase in maternal and fetal haematocrit. At gestational day 20, maternal plasma urate and L-cysteine concentrations, and placental levels of 4-hydroxynonenal and heat shock protein 70 were increased while placental heat shock protein 90 levels were decreased in hypoxic pregnancy. The induction of maternal circulatory and placental molecular indices of oxidative stress in hypoxic pregnancies was prevented by maternal treatment with vitamin C. Maternal hypoxia during pregnancy with or without vitamin C increased placental weight, but not total or compartmental volumes. Maternal treatment with vitamin C increased birth weight in both hypoxic and normoxic pregnancies. The data show that maternal hypoxia independent of maternal undernutrition promotes maternal and placental indices of oxidative stress, effects that can be prevented by maternal treatment with vitamin C in hypoxic pregnancy. While vitamin C may not be the ideal candidate of choice for therapy in pregnant women, and taking into consideration differences in ascorbic acid metabolism between rats and humans, the data do underlie that antioxidant treatment may provide a useful intervention to improve placental function and protect fetal growth in pregnancy complicated by fetal hypoxia.
    The Journal of Physiology 01/2012; 590(Pt 6):1377-87. DOI:10.1113/jphysiol.2011.226340 · 4.54 Impact Factor
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    • "An increase of NADP + and 2,3-BPG concentrations and integral amount of phosphorates has also been observed (Wójcicka et al. 1977). The disrupted adenine metabolites and disrupted balance between the speed of ROS production in a cell and their degradation accompanying hypoxia during the periparturient period may lead to different complications such as preeclampsia, abortion, premature birth and hypertension (Arikan et al. 2001; Bracci et al. 2002; Wender-Ożegowska et al. 2004; Bainbridge and Roberts 2008). "
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    ABSTRACT: The aim of this study was to examine the relationships between the erythrocyte concentrations of ATP, ADP, AMP, NAD(+), NADP(+) and adenylate energy charge (AEC) and their metabolites: inosine (Ino), hypoxanthine (Hyp), uric acid (UA), selected blood antioxidants: superoxide dismutase (SOD), glutathione reductase (GR) of goats during the periparturient period. The study was conducted on 12 clinically healthy pregnant goats (Capra hircus) - 75% genotype of the Polish noble white aged between 2-3 years. Blood was taken from the external jugular vein early in the morning before feeding and obtained twice (4 weeks and 1 week) before delivery and twice (2 and 3 weeks) after delivery. The ATP concentration did not change significantly. One week before delivery ADP, AMP and Ino concentrations were significantly higher and AEC value significantly lower compared to values in the third week after delivery (p <= 0.02, p <= 0.05, p <= 0.03 and p <= 0.01, respectively). One week before and two weeks after delivery we observed a significant increase in SOD and GR activities and an increase in NAD(+) and NADP(+) concentrations but a significant decrease in Hyp and UA concentrations. Constant ATP concentration and the changes in the dynamics and tendency of Hyp and UA concentrations show that in the periparturient period in goats, purine metabolism undergoes adaptive changes. The balance between resynthetic processes and adenine nucleotide degradation is retained in order to level the oxygen and energy lacks. The results of our study show that the maintenance of prooxidative homeostasis in goats of peripartal period depends mainly on enzymatic mechanisms.
    Acta Veterinaria Brno 12/2010; 79(4):571-579. DOI:10.2754/avb201079040571 · 0.45 Impact Factor
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