allopurinol and Fetal-Growth-Retardation

The objective of this study was to identify the relationship between fetal growth restriction (FGR) and oxidative stress. The mechanisms that protect against oxidative stress in the local microenvironment were investigated by comparing the activities of the markers, both in the circulation and myometrium.. Myometrial tissue and serum levels of malondialdehyde (MDA), xanthine oxidase (XO), catalase (CAT) and superoxide dismutase (SOD) markers were measured in 20 FGR and 20 healthy pregnancies.. The mean duration of gestation at delivery was shorter (P = 0003) and the mean birthweight was lower P < 0001) in the FGR study group compared with the control group, as expected. While MDA and CAT concentrations were higher in the serum (P < 0.02 and P < 0.01, respectively), but lower in the myometrial samples (P < 0.01) in the FGR versus the control group, XO and myometrial SOD values were comparable in both groups.. Although our data demonstrated that FGR is associated with oxidative stress, the exact role and mechanism of the oxidant and antioxidant imbalance is obscure. We speculate that despite limited local synthesis of CAT, effective and efficient removal of MDA in the uterine environment explains high MDA and CAT serum concentrations in women with FGR. Alternatively, a well-functioning myometrial system could rescue the fetus from reactive oxygen species, as demonstrated by lowered MDA and depleted CAT resulting from hyperconsumption. Elevated serum MDA and CAT levels in the serum may reflect the 'spillover' of these markers from the uterus to the circulation.

Topics: Adult; Biomarkers; Catalase; Female; Fetal Growth Retardation; Humans; Malondialdehyde; Myometrium; Oxidative Stress; Pregnancy; Superoxide Dismutase; Xanthine Oxidase; Young Adult

Maternal metabolic diseases increase offspring risk for low birth weight and cardiometabolic diseases in adulthood. Excess fructose consumption may confer metabolic risks for both women and their offspring. However, the direct consequences of fructose intake per se are unknown. We assessed the impact of a maternal high-fructose diet on the fetal-placental unit in mice in the absence of metabolic syndrome and determined the association between maternal serum fructose and placental uric acid levels in humans. In mice, maternal fructose consumption led to placental inefficiency, fetal growth restriction, elevated fetal serum glucose and triglyceride levels. In the placenta, fructose induced de novo uric acid synthesis by activating the activities of the enzymes AMP deaminase and xanthine oxidase. Moreover, the placentas had increased lipids and altered expression of genes that control oxidative stress. Treatment of mothers with the xanthine oxidase inhibitor allopurinol reduced placental uric acid levels, prevented placental inefficiency, and improved fetal weights and serum triglycerides. Finally, in 18 women delivering at term, maternal serum fructose levels significantly correlated with placental uric acid levels. These findings suggest that in mice, excess maternal fructose consumption impairs placental function via a xanthine oxidase/uric acid-dependent mechanism, and similar effects may occur in humans.

Topics: Allopurinol; AMP Deaminase; Animals; Disease Models, Animal; Female; Fetal Growth Retardation; Fructose; Mice; Oxidative Stress; Placenta; Placental Insufficiency; Pregnancy; Triglycerides; Uric Acid; Xanthine Oxidase

The objectives of this study were to determine the role of oxidative stress in intrauterine growth restriction (IUGR) and to investigate the possible molecular mechanism(s) leading to oxidant stress in IUGR.. Parameters of the oxidative and antioxidant system were evaluated in maternal plasma, umbilical cord blood, and placental tissue of pregnant women with IUGR fetuses. The same samples were obtained from women with normal pregnancies and were evaluated.. The results of this study indicate that while the levels of malondialdehyde (MDA) and xanthine oxidase (XO) were higher in maternal plasma, umbilical cord plasma, and placental tissues of the patients with IUGR when compared to the control group [MDA: 142.8 +/- 18.0 vs. 86.4 +/- 22.5 nmol/ml, 151.6 +/- 25.8 vs. 93.3 +/- 7.4 nmol/ml, and 0.72 +/- 0.19 vs. 0.42 +/- 0.09 nmol/mg protein, respectively (for all p < 0.0005); XO: 1.251 +/- 0.674 vs. 0.20 +/- 0.019 mIU/ml (p < 0.0005), 1.97 +/- 0.73 vs. 0.237 +/- 0.143 mIU/ml (p < 0.0005), and 0.023 +/- 0.0012 vs. 0.012 +/- 0.004 mIU/ml (p < 0.025), respectively], the levels of antioxidant potential were identified to be lower in maternal plasma, umbilical cord plasma, and placental tissues of the patients with IUGR: 63.3 +/- 11.9 vs. 198.0 +/- 31.9 U/ml (p < 0.0005), 32.6 +/- 3.7 vs. 206.5 +/- 27.1 U/ml (p < 0.0005), and 0.56 +/- 0.23 vs. 1.16 +/- 0.29 U/ml (p < 0.0005), respectively. On the other hand, the activities of adenosine deaminase of the IUGR patients were higher than those of the control group in maternal plasma (204.8 +/- 103.5 vs. 115.6 +/- 31.8 U/l, p < 0.01) and umbilical cord blood samples (584.2 +/- 285.2 vs. 147.9 +/- 44.8 U/l, p < 0.0005) which may suggest that oxidative stress has a role in IUGR. Moreover, an increased superoxide dismutase activity in maternal plasma (128.2 +/- 37.4 vs. 88.8 +/- 16.6 U/ml, p < 0.005) and cord blood (162.1 +/- 37.0 vs. 116.6 +/- 20.7 U/ml, p < 0.005) and an increased glutathione peroxidase activity in maternal plasma (1.83 +/- 0.26 vs. 1.47 +/- 0.31 IU/ml, p < 0.01) and placental tissue (0.007 +/- 0.0015 vs. 0.003 +/- 0.0012 IU/ml, p < 0.0005) were detected, while decreased catalase activities in cord blood (23,717 +/- 3,538 vs. 16,397 +/- 2,771 IU/ml, p < 0.0005) and placental tissue (47.2 +/- 17.2 vs. 70.7 +/- 11.3 IU/ml, p < 0.005) were identified in IUGR groups.. In the light of the results of this study, it can be stated that the oxidative stress increases in patients with IUGR. Providing high-risk patients with an antioxidant may be useful in the prevention or treatment of IUGR, although it is a condition with no certain treatment outcome.

Topics: Adult; Case-Control Studies; Female; Fetal Blood; Fetal Growth Retardation; Humans; Lipid Peroxidation; Malondialdehyde; Oxidative Stress; Placenta; Pregnancy; Pregnancy Trimester, Third; Xanthine Oxidase

We previously reported that intrauterine undernutrition increased the oxidative stress by decreasing superoxide dismutase activity. In the present study, we tested whether NADPH oxidase, xanthine oxidase, cyclooxygenase or nitric oxide synthase are responsible for the increased O(2)(-) generation observed in rats submitted to intrauterine undernutrition. In addition, we investigated the effect of angiotensin II (ANG II) on O(2)(-) production via activation of NADPH oxidase.. Female pregnant Wistar rats were fed either normal or 50% of the normal intake diets, during the whole gestational period. At 16 weeks of age, the rats were used for the study of intravital fluorescence microscopy; microvascular reactivity, local ANG II concentration and AT(1), p22(phox) and gp91(phox) gene expression. In this study only the male offspring was used.. Treatment of mesenteric arterioles with the xanthine oxidase inhibitor oxypurinol, the nitric oxide synthase inhibitor L-NAME or the cyclooxygenase inhibitor diclofenac did not significantly change superoxide production. Thus, these vascular sources of superoxide were not responsible for the increased superoxide concentration. In contrast, treatment with the NADPH oxidase inhibitor apocynin significantly decreased superoxide generation and improved vascular function. On the other hand, intrauterine undernutrition did not alter the gene expression for p22(phox) and gp91(phox). The fact that the local ANG II concentration was increased and the attenuation of oxidative stress by blocking AT(1) receptor with losartan, led us to suggest that ANG II induces O(2)(-) generation in intrauterine undernourished rats.. Our study shows that NADPH oxidase inhibition attenuated superoxide anion generation and ameliorated vascular function in rats submitted to intrauterine undernutrition. Although it is not clear which mechanisms are responsible for the increase in NADPH oxidase activity, a role for ANG II-mediated superoxide production via activation of NADPH oxidase is suggested.

Topics: Acetophenones; Angiotensin II; Animals; Cyclooxygenase Inhibitors; Diclofenac; Enzyme Inhibitors; Female; Fetal Growth Retardation; Male; Mesenteric Arteries; Microscopy, Fluorescence; NADPH Oxidases; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Oxypurinol; Pregnancy; Random Allocation; Rats; Rats, Wistar; Renin-Angiotensin System; Superoxides; Vasodilation; Xanthine Oxidase

Alterations in maternal plasma arginine concentration accompany normal pregnancy. Nitric oxide is synthesized from L-arginine and influences fetal growth. We hypothesized that L-arginine would influence fetal growth and hypoxia-induced uricemia in a maternal hypoxia-induced fetal growth restriction model.. Fetal growth on day 21 of gestation was assessed in timed pregnant Wistar rats with or without exposure to maternal hypobaric hypoxia. Animals exposed to hypoxia received either no supplement or supplementation of drinking water with 0.2% L-arginine, 2% L-arginine, or 2% glycine. On day 21 of gestation, fetuses were delivered by hysterotomy and fetal and placental weights were obtained. Maternal and fetal plasma were assayed for uric acid as an index of tissue hypoxia. Xanthine oxidase and xanthine dehydrogenase, precursors of uric acid and reactive oxygen species, were assayed in maternal tissue. Results were analyzed by analysis of variance with correction for multiple comparisons.. Exposure of rats on normal diets to hypoxia resulted in a 30% reduction in fetal weights. L-Arginine, 2% or 0.2%, prevented the reduction in fetal weight (p < 0.0001). Isocaloric and isonitrogenous supplementation with glycine did not influence hypoxia-induced fetal growth restriction.. L-Arginine, but not glycine, ameliorates maternal hypoxia-induced fetal growth restriction in the rat.

Topics: Animals; Arginine; Atmospheric Pressure; Diet; Embryonic and Fetal Development; Endothelins; Female; Fetal Growth Retardation; Glycine; Hypoxia; Nitric Oxide; Pregnancy; Rats; Rats, Wistar; Uric Acid; Xanthine Dehydrogenase; Xanthine Oxidase