Lipoperoxidation and antioxidant enzymes activity in pregnancy complicated with hypertension

Objective: To assess maternal circulating levels of lipid peroxidation breakdown products and antioxidant enzymes activity in pregnancies complicated with hypertension. Study design: Ten women with uncomplicated pregnancies and nine women with hypertension antedating pregnancy were prospectively sampled. Eight women, who had developed preeclampsia, were also cross-sectionally included. Twenty healthy non pregnant volunteers were the control group. Thiobarbituric acid reactive substances (TBA-RS), as lipid peroxidation products, and the activity of catalase (CAT), glutathione peroxidase (GPX) and superoxide dismutase (SOD), as antioxidant enzymes, were assayed in red blood cell hemolysates. A prooxidant/antioxidant (P/A) ratio (TBA-RS/CAT + GPX + SOD) was determined from the mean value of the volunteers. Results: In women with chronic hypertension, TBA-RS levels were higher than those in normal pregnant women, whereas antioxidant enzymes activities were either stable or decreased. Therefore the P/A ratio was progressively lower in the second and third trimester. Similar results were found in patients with preeclampsia. Conclusions: Normal gestation induces an increase of lipid peroxidation products, whereas antioxidant activity seems stable. In pregnancies complicated by chronic hypertension, a deficiency of the oxidative system balance is detectable, which consistently progresses in the second and third trimester, strongly suggesting a failure of the protective mechanisms.     

Impaired antioxidant activity in women with pre-eclampsia.

OBJECTIVE: To investigate antioxidant activity of sera and the plasma blood levels of two potent antioxidant in women with pre-eclampsia and normotensive pregnancies. STUDY DESIGN: The antioxidant activity of sera and the blood levels of ascorbic acid and alpha-tocopherol were assayed in women with normal pregnancies (n = 33), mild pre-eclampsia (n = 8), and severe pre-eclampsia (n = 16) between 20 and 40 weeks' gestation. Ascorbic acid and alpha-tocopherol concentrations were analyzed by high-performance liquid chromatography. Antioxidant activity of sera was measured as the percent inhibition of spontaneous autoxidation of a standard brain homogenate. RESULTS: Plasma levels of ascorbic acid in women with mild and severe pre-eclampsia were significantly lower than normal pregnancies (P < 0.05). Sera alpha-tocopherol levels were significantly decreased only in severe pre-eclampsia (P < 0.05). Sera antioxidant activity were significantly decreased in mild (73%) and severe (51%) pre-eclampsia compared with normal (86%) pregnancies (P = 0.02, P = 0.000, respectively). CONCLUSIONS: In women with pre-eclampsia, sera antioxidant activity and antioxidant level of plasma are decreased when compared with normotensive pregnancies. Impaired antioxidant activity and the reduction of antioxidant levels which increase the level of lipid peroxidation products may cause peroxidative damage of vascular endothelium and result in clinical symptoms of pre-eclampsia.     

Augmented oxidative stress as well as antioxidant capacity in maternal circulation in preeclampsia

OBJECTIVES: Isoprostanes are stable markers of oxidative stress. We wanted to assess maternal circulating levels of total 8-isoprostane and indices of antioxidant capacity in preeclampsia compared to uneventful pregnancies. STUDY DESIGN: Total 8-isoprostane concentrations, FRAP (ferric reducing ability of plasma), Vitamin E and d-ROM (diacron reactive oxygen metabolites) were measured in maternal venous blood samples from preeclamptic (n=21) and uncomplicated (n=38) pregnancies at cesarean section. RESULTS: Median total 8-isoprostane concentration was elevated in preeclampsia compared to uncomplicated pregnancies (354 and 218 pg/mL, P=0.02). Median FRAP level was also elevated in preeclampsia compared to uncomplicated pregnancies, but to a lesser degree than 8-isoprostane. A positive correlation between 8-isoprostane and previously analyzed placenta-derived sFlt1 (soluble fms-like tyrosine kinase 1) levels in the maternal circulation was found in preeclampsia. CONCLUSION: We found a relative more increase for the oxidative stress marker (8-isoprostane) than for the antioxidant capacity (FRAP) in preeclampsia compared to uneventful pregnancies.     

The role of placental oxidative stress and lipid peroxidation in preeclampsia

Preeclampsia is a complex multisystem disorder exclusively seen in human species that is characterized by hypertension and proteinuria. This disorder has the highest maternal and fetal morbidity and mortality of all pregnancy-related complications. Growing evidence suggests that placental oxidative stress is involved in the etiopathogenesis of preeclampsia. Reduced perfusion as a result of abnormal placentation leads to ischemia reperfusion injury to the placenta. Placental oxidative stress, which results from the ischemia reperfusion injury, is being increasingly reported to be involved in the etiopathogenesis of preeclampsia. It has been proposed as a promoter of lipid peroxidation and the endothelial cell dysfunction that is commonly seen in this condition. Although preeclampsia is characterized by increased lipid peroxidation and diminished antioxidant capacity, there is no consensus regarding causality of lipid peroxidation in preeclampsia. In this article, we address the question of the biologic association of lipid peroxidation and preeclampsia. Lipid peroxidation and leukocyte activation may play a pivotal role in endothelial cell dysfunction. We also review the different factors that have been proposed to cause endothelial cell dysfunction in preeclampsia, trials investigating the role of antioxidant supplementation in preeclampsia, and the lack of consensus among the trials. Additional longitudinal studies are necessary to determine if the various oxidative stress biomarkers estimated early in pregnancy can be narrowed to a single marker for predicting preeclampsia. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to recall that placental oxidative stress is involved in the etiopathogenesis of preeclampsia, state that placental oxidative stress results from ischemic reperfusion injury, and explain that ischemic reperfusion injury is a promoter of lipid peroxidation and endothelial cell dysfunction seen in preeclampsia.     

Significance of changes in lipid peroxides and antioxidant enzyme activities in pregnant women with preeclampsia and eclampsia

This review addresses the general hypothesis that the pathogenesis of preeclampsia and eclampsia are related to an imbalance of increased oxidative stress and lipid peroxidation coupled with a deficiency of antioxidant protection. Accordingly, this study was initiated to assess total antioxidant status and free-radical activity in preeclampsia and eclampsia. The patients studied were 44 healthy pregnant women and 45 women with hypertension classified as having preeclampsia (n=27), and eclampsia (n=18). The serum levels of lipid peroxide were significantly increased (p<0.0001) and antioxidant enzyme activities (superoxide dismutase and glutathione levels) in erythrocytes were significantly decreased (p<0.0001) in women with preeclampsia and eclampsia compared with the controls. The groups of preeclampsia and eclampsia had similar values of catalase activities as the controls (p>0.05). There were no correlations between serum levels of lipid peroxide and antioxidant enzyme activities or systolic-diastolic blood pressure of pregnant women with preeclampsia and eclampsia. The mean systolic and diastolic blood pressure, the serum lactate dehydrogenase (LDH) and aspartate transaminase (AST) levels of preeclamptic and eclamptic women were high, whereas haemoglobin (Hb), Hematocrit (Htc) and platelet levels were lower than those of the control subjects (p<0.0001). There were no differences in mean gestational week, whereas the mean age of eclamptic women was lower than that of the other two groups (p<0.001). The serum levels of Alanine-transaminase (ALT) and urea in eclamptic women were significantly higher compared with the other two groups (p<0.0001), whereas creatinine levels were lower than those of the other two groups (p<0.05). Our findings give support to those few studies considering lipid peroxidation as an important factor in the pathogenesis of preeclampsia and eclampsia. Further studies are needed to clarify the relations between lipid peroxidation and antioxidative function and their pathophysiological significance in preeclampsia and eclampsia.     

Lipid peroxidation and Ca-ATPase activity of basal plasma membranes of syncytiotrophoblast from normotensive pregnant women

BACKGROUND: The Ca-ATPase activity of the plasma membranes of several tissues of preeclamptic pregnant women is significantly reduced when compared with the values of normotensive pregnant women. This has been explained considering the raise in the level of lipid peroxidation of the plasma membranes with preeclampsia. In this work we studied the effect of lipid peroxidation of syncytiotrophoblast basal (fetal facing) plasma membranes from normotensive pregnant women, on their level of Ca-ATPase activity. METHODS: The syncytiotrophoblast basal (fetal facing) plasma membranes from normotensive pregnant women were isolated and irradiated with ultraviolet (UV) light (254 nm). The membranes were then assayed for Ca-ATPase activity and lipid peroxidation by TBARS. RESULTS: The UV irradiation raises the level of lipid peroxidation of the membranes, producing a concomitant inhibition of their Ca-ATPase activity. Presence of the antioxidant butylated hydroxytoluene during the UV irradiation of the membranes prevents increase in their level of lipid peroxidation and hence the inhibition of their Ca-ATPase activity. CONCLUSION: These results give a strong support to the hypothesis that the lowered Ca-ATPase activity already described for plasma membranes of several tissues of preeclamptic women is the consequence of the increased level of lipid peroxidation shown by these membranes.     

Oxidative stress in preeclampsia

Preeclampsia is the main case of maternal and perinatal mortality. In women with preeclampsia antioxidant activity of plasma is decreased. Increased levels of of lipid peroxidation products may case peroxidative damage of vascular endotelium and result in clinical symptoms of preeclampsia.     

Lipid peroxidation and antioxidants in preeclampsia

OBJECTIVE: To determine the changes in plasma levels of lipid peroxide, vitamin E and vitamin C in women with preeclampsia and to investigate their relationship with diastolic blood pressure. STUDY DESIGN: Cross sectional study consisting of 22 preeclamptic and 21 healthy pregnant women. Fasting venous blood samples were collected during the antepartum period and plasma levels of malondialdehyde, alpha-tocopherol and ascorbic acid were measured. RESULTS: In the preeclamptic group malondialdehyde, a lipid peroxidation product, was significantly increased, while vitamins E and C were significantly decreased compared to healthy pregnant women. A strong correlation was detected between malondialdehyde and antioxidant factors (vitamins E and C) with blood pressure. CONCLUSION: Our findings are consistent with previous studies suggesting that lipid peroxidation is an important factor in the pathogenesis of preeclampsia. In preeclampsia, antioxidant nutrients are excessively utilised to counteract the cellular changes mediated by free radicals.     

Increased lipolytic activity and high ratio of free fatty acids to albumin in sera from women with preeclampsia leads to triglyceride accumulation in cultured endothelial cells.

OBJECTIVE: The null hypothesis of this study was that the triglyceride accumulation in endothelial cells exposed to sera from preeclamptic women was determined by the presence of triglyceride-rich lipoproteins in the sera. STUDY DESIGN: The accumulation of triglycerides in cultured endothelial cells was studied using incorporation of tritiated glycerol. RESULTS: Triglyceride-rich lipoproteins in the patient sera contributed little to the endothelial triglyceride accumulation. However, sera from preeclamptic women were found to have a higher molar ratio of free fatty acids to albumin compared with sera from women with normal pregnancies (1.6 +/- 0.5 vs 0.9 +/- 0.4, respectively, p less than 0.025). In addition, sera from preeclamptic women, compared with sera from normal pregnancies, showed enhanced lipolytic activity (release of free fatty acids 0.85 +/- 0.29 vs 0.17 +/- 0.16 mmol/ml per 24 hours, respectively; p less than 0.025) that further increased the free fatty acids/albumin ratio. CONCLUSION: Sera from preeclamptic women have both a higher ratio of free fatty acids to albumin and increased lipolytic activity, resulting in enhanced endothelial uptake of free fatty acids, which are further esterified into triglycerides.     

Circulating biomarkers of oxidative stress in complicated pregnancies

Increased lipid peroxidation (LPO) and reduced antioxidant activity may contribute to the development of complications in pregnancy. The present study discusses the possibility of LPO and antioxidant activity in both maternal and umbilical cord blood as an indicator of oxygen radical activity. For this aim, pregnancies with hypertension and pre-eclampsia, diabetes mellitus (insulin dependent diabetes mellitus and gestational diabetes mellitus), oligohydramnios and abruptio placentae, as well as a healthy control group, were subjected in the present study. Simultaneous determination of glutathione S-transferase (GST), selenium dependent glutathione peroxidase (Se-GPx), catalase (CAT) activities and thiobarbituric acid reactive-substances (TBARs) levels were carried out in maternal erythrocyte and plasma in the antenatal period (in the third trimester) and immediately after the delivery. The same oxidative stress-related parameters were determined in umbilical cord blood as well. Erythrocyte GST activity was significantly increased in insulin-dependent diabetic pregnancy (IDDP) when compared to the control (P<0.05). Erythrocyte Se-GPx activity was found to be significantly increased in hypertensive preeclamptic pregnancy (HPP) (P<0.05) and in IDDP (P<0.05). Alterations in enzyme activities were accompanied by a simultaneous significant increase in the levels of TBARs in plasma samples of HPP (P<0.05), and IDDP (P<0.05). Enzyme activities were found to be significantly lower in cord blood samples than the maternal values, except GST. This enzyme represents about two- to threefold higher activity than those of the maternal activity in uncomplicated and complicated groups. Cord blood erythrocyte and plasma Se-GPx and CAT activities were decreased significantly in the HPP group when compared to the maternal value (P<0.05). Cord blood erythrocyte CAT activity was significantly decreased in the HPP group compared to the control (P<0.05). Cord blood TBARs levels were significantly lower than the before deliveries maternal value in the HPP group (P<0.05). No difference was detected between umbilical cord blood and maternal blood TBARs levels after delivery. The results of the present study suggest that oxidative stress and subsequent lipid peroxidation accompany the complications of hypertension, preeclampsia and diabetes mellitus in pregnancy. Maternal erythrocyte GST activity seems to be a sensitive indicator of oxidative stress in IDDP before delivery. The same enzyme can be used in cord blood as a biomarker of oxidative stress upon a sudden increase in oxygenation during delivery. These multiparameter biomarkers can also be used in monitoring the efficiency of antioxidant supplementation in complicated pregnant women, as has recently been suggested for diabetic and preeclamptic pregnancies.     

Obesity and oxidative stress: a direct link to preeclampsia?

Overweight is associated with alterations in lipid concentrations and an activation of inflammatory markers and both of these metabolic abnormalities are characteristic of preeclamptic pregnancies before the onset of clinically evident disease. Reactive oxygen species, particularly superoxide anions, evoke endothelial cell activation through many pathways. Markers of lipid peroxidation, including malondialdehyde and 8-epiprostaglandin-F2α, is increased in the plasma of women with preeclampsia, and the low concentrations of water- and lipid-soluble antioxidants in the plasma and the placenta further suggest a state of oxidative stress. This review focuses in the relation between maternal obesity, oxidative stress with development of preeclampsia.     

MATRIX METALLOPROTEINASE-2 IS ELEVATED IN THE PLASMA OF WOMEN WITH PREECLAMPSIA

Objective: We have recently demonstrated that matrix metalloproteinase-2 (MMP-2) alters vascular function through cleavage of vasoactive peptides, resulting in increased vasoconstriction and reduced vasodilation. We, therefore, hypothesized that MMP levels are increased in women with preeclampsia. In addition, because vascular endothelial growth factor (VEGF) has been implicated in the pathophysiology of preeclampsia and is involved in angiogenesis that requires the release of proteases to allow for migration of endothelial cells, we hypothesized that VEGF increases release of MMPs from endothelial cells.

Methods: We used zymographic analysis to evaluate MMP-2/MMP-9 levels in plasma of women with preeclampsia (n=12) compared to women with uncomplicated pregnancies (n=12). In addition, we evaluated the changes in the levels of MMP-2 and MMP-9 as well as tissue inhibitors of MMPs (TIMP-1 and TIMP-2) released by cultured human umbilical vein endothelial cells in response to VEGF (0.1–10 ng/mL).

Results: Our data showed that plasma MMP-2 levels were significantly higher in women with preeclampsia compared to women with uncomplicated pregnancies (arbitrary intensity units: 690 ±111 and 252 ±56, respectively, p<0.05). MMP-9 levels were below the level of detection. In addition, VEGF stimulated endothelial MMP-2 and MMP-9 release in a concentration- and time-dependent (6–24 h) manner. Moreover, VEGF stimulation of MMP release occurs without significantly affecting the release of TIMP-1 and TIMP-2.

Conclusions: These data suggest that VEGF promotes secretion of MMPs from endothelial cells that, in turn, could alter vascular function in women with preeclampsia.     

子(癎)前期孕妇中性粒细胞相关因子与胎儿的关系

目的:了解中性粒细胞在子前期胎儿中的状态,探讨其在胎儿患病中的作用。方法:采用流式细胞术检测20例子前期患者和20例正常妊娠孕妇肘静脉血和脐静脉血中中性粒细胞粘附分子CD11b的表达,同时采用酶联免疫吸附实验检测两组血浆IL-8和弹性蛋白酶的浓度。结果:①子前期组母体静脉血CD11b的平均对数荧光强度指数、血浆IL-8和弹性蛋白酶的浓度均高于正常妊娠组(P<0.05);②子前期组脐静脉血CD11b的平均对数荧光强度指数高于正常妊娠组(P<0.05),但血浆IL-8和弹性蛋白酶的浓度与正常妊娠组比较无统计学差异(P>0.05);③胎儿脐静脉血中的中性粒细胞CD11b平均对数荧光强度指数与母体静脉血中的中性粒细胞CD11b平均对数荧光强度指数有正相关关系(r=0.590,P<0.01)。结论:子前期胎儿中性粒细胞的激活与母体中性粒细胞的激活相关,胎儿循环中存在中性粒细胞的激活,推测中性粒细胞在子前期胎儿病率中有一定作用。     

Mitogenic activity is increased in the sera of preeclamptic women before delivery

There is increasing evidence that endothelial cell injury and altered endothelial cell function play an important role in the pathogenesis of preeclampsia. Endothelial cell injury can lead to the secretion of potent mitogens by activating platelets and directly through the increased production of peptide growth factors by endothelial cells themselves. This study was undertaken to test the hypotheses that increased secretion of mitogenic factors is a feature of preeclampsia and that this activity could be detected in the serum of preeclamptic women. Paired serum samples were collected in early labor and again at 24 to 48 hours post partum from term patients with preeclampsia (n = 15) and normal pregnant controls (n = 14). A bioassay was used to quantify mitogenic activity in these paired samples by assessing their ability to stimulate the incorporation of tritiated thymidine into deoxyribonucleic acid of confluent, quiescent (GO stage) human fibroblasts in monolayer culture. Mitogenic activity was significantly increased in prepartum, preeclamptic sera compared with normal controls and diminished rapidly postpartum to levels equivalent to normal pre- and postpartum serum. These findings are consistent with endothelial cell injury, a process that we believe plays a central role in the pathophysiology of the preeclamptic syndrome.     

内皮脂酶在重度子痫前期孕妇血清、胎儿脐血中的表达及意义

目的：研究重度子痫前期（PE）孕妇血清、胎儿脐血中内皮脂酶（EL）的表达及其与血脂代谢的关系,探讨EL在PE发病中的作用。方法：选取行剖宫产分娩的重度PE单胎孕妇30例为病例组,行剖宫产分娩的30例正常孕妇为对照组。ELISA法检测孕妇血清及胎儿脐血中的EL浓度;用全自动生化分析仪检测血脂浓度。分析EL浓度与血脂指标的相关性。结果：（1）与正常孕妇比较,重度PE组孕妇的血清三酰甘油（TG）浓度增高,高密度脂蛋白（HDL）浓度降低,动脉硬化指数（AI）增高,差异均显著（P=0.003）。重度PE组胎儿脐血中TG、总胆固醇（CHO）、低密度脂蛋白（LDL）及AI均显著高于对照组（P=0.000）。（2）重度PE组孕妇的血清EL浓度显著高于对照组（692.96ng／mlVS441.21ng／ml,P=0.000）,而两组胎儿脐血中的EL浓度无显著差异。（3）孕妇血清EL浓度与TG浓度呈正相关（r=0.354,P=0.006）,与HDL浓度呈负相关（r=-0.451,P=0.000）。结论：重度PE孕妇及胎儿脐血中均存在血脂异常,重度PE孕妇血清中EL浓度显著增高。提示EL影响血脂代谢,且其可能与PE的发病机制有关。     

Preeclampsia is associated with increased susceptibility of serum lipids to copper-induced peroxidation in vitro

BACKGROUND: Several reports suggest preeclampsia to be associated with oxidative stress. In view of potential experimental artifacts in these studies, we tested the effect of preeclampsia on the oxidizibility of maternal serum lipids, using an optimized ex vivo method. METHODS: This prospective study included 28 pregnant women with preeclampsia and 28 women matched for maternal and gestational age with normal pregnancies. Venous blood was drawn from the consenting women. Serum levels of lipid peroxidation products and the kinetics of copper-induced oxidation ex vivo were monitored spectroscopically by continuous recording of absorbance at 245 nm. RESULTS: The initial optical density (OD) at 245 nm, attributed to preformed products of lipid peroxidation, was higher in the women with preeclampsia than in the controls (1.26 +/- 0.02 vs. 1.17 +/- 0.02 OD units; p = 0.01). The lag phase preceding oxidation, reflecting resistance of serum lipids to oxidation, was significantly shorter in the preeclampsia group than in the controls (47.4 +/- 2.3 vs. 57.6 +/- 4.0 min; p = 0.027). CONCLUSIONS: High levels of serum hydroperoxides and increased susceptibility of serum lipids to copper-induced peroxidation ex vivo indicate preeclampsia to be associated with high oxidative stress. The role of this high oxidizibility in the pathogenesis of preeclampsia has yet to be evaluated.     

Oxidant-antioxidant system changes relative to placental-umbilical pathology in patients with preeclampsia.

OBJECTIVE: It is speculated that lipid peroxidation is responsible for the pathologic changes that occur in the uteroplacental vasculature of women with preeclampsia. The aim was to investigate this proposed relationship. MATERIALS AND METHODS: The prospective study involved 90 pregnant women. Thirty had mild preeclampsia, 30 had severe preeclampsia, and 30 were healthy pregnant women (controls). The data collected for each case were umbilical cord and placental pathologies, plasma malondialdehyde (MDA) level, and levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity in erythrocytes. Group findings were compared. RESULTS: The mean MDA level in the severe preeclampsia group was higher than the corresponding findings in the mild preeclampsia and control groups (p < 0.001 for both). Also, the MDA level in the mild preeclampsia group was significantly higher than was the control level (p < 0.001). The mean SOD activity level in the severe preeclampsia group was lower than the corresponding results in the mild preeclampsia and control groups (p < 0.001 for both). The mean GSH-Px levels in the mild and severe preeclampsia groups were both significantly lower than was the corresponding finding in the control group (p < 0.01). Compared to the control group, both preeclampsia groups had significantly higher frequencies for placental infarction, villous fibrosis, increased numbers of syncytial nodes, and thickening of vessel walls and lumen obliteration (p < 0.001 for all). Villous fibrinoid necrosis, perivillous fibrosis, and increased villous vascularization were also significantly more frequent in both preeclampsia groups than in the control group, but the differences for these parameters were smaller (p < 0.01 for all). Examination of the samples from the placental ends of the umbilical cords revealed significantly higher frequencies of endothelial irregularity, endothelial shedding, and basal membrane thickening in both preeclampsia groups than in those of the control group (p < 0.001). The same findings were noted in the middle sections of the cords (p < 0.001). At the fetal ends of the umbilical cords, both preeclampsia groups had higher frequencies of endothelial irregularity than did the control group (p < 0.001); however, the frequencies of the more severe pathologic findings (endothelial shedding, basal membrane thickening) in the three groups were similar. CONCLUSION: The frequencies of pathologic changes in the placenta and umbilical vessels of women with preeclampsia parallel the severity of this condition. These changes also parallel plasma levels of MDA, the end product of lipid peroxidation.     

Effect of physiologic levels of glutamine on ICAM-1 expression in endothelial cells activated by preeclamptic plasma

OBJECTIVE: To investigate whether the plasma glutamine (GLN) concentration would be depleted in pregnant women with preeclampsia and whether administering GLN comparable to physiologic levels would decrease cellular adhesion molecule expression in human umbilical vein endothelial cells (HUVECs) induced by plasma in preeclamptic women. STUDY DESIGN: We assessed plasma GLN levels from blood samples collected from 20 women with preeclampsia and 10 normal pregnant women. HUVECs were cultured in medium-199, containing fetal calf serum, antibiotics and growth factor, at different concentrations (0, 300, 500 microM) of GLN for 24 hours. We stimulated those cells for 1.5-6.0 hours with sera from patients with preeclampsia and then determined the expression of intercellular cell adhesion molecules (ICAM)-1 and vascular cell adhesion molecules (VCAM)-1 on endothelial cells by flow cytometry. RESULTS: Women with preeclampsia had significantly lower plasma GLN concentrations as compared with normal pregnant women. There were no differences in VCAM-1 expression in HUVECs among various GLN concentrations at each time point. However, ICAM-1 expression in HUVECs was significantly lower in the 500-microM GLN group than in the 0- and 300-microM groups at 3, 4.5 and 6 hours. CONCLUSION: This study showed that plasma from women with preeclampsia had significantly lower GLN levels than that from normal pregnant women and that administering GLN at physiologic levels reduces HUVEC ICAM-1 expression induced by preeclamptic plasma.     

Lipid peroxidation and antioxidant activity in patients in labor with nonreassuring fetal status

OBJECTIVE: The aim of our study was to evaluate lipid peroxidation products and antioxidant enzyme activity in placental tissue and umbilical cord blood, as a marker for fetal hypoxia in patients in labor with nonreassuring fetal status. STUDY DESIGN: Umbilical cord arterial blood and placental tissue samples were collected from 24 patients with term pregnancies in labor and nonreassuring fetal heart rate (FHR) patterns (study) and 24 women with normal pregnancies in labor and normal FHR tracings (controls) for determination of malondialdehyde (MDA) as a marker for lipid peroxidation and superoxide dismutase (SOD) for the antioxidant activity. Measured values were compared statistically between two groups using independent samples t-test or Mann-Whitney U-test. RESULTS: The median 1min Apgar score was 8 (range 4-9) in the study group and 9 (range 8-10) in the control group, respectively (p < 0.001). There was no statistically significant difference between study and control groups in terms of mean 5 min Apgar scores (p > 0.05). Placental MDA levels in patients with nonreassuring fetal status were found to be significantly elevated compared to the control group (12.14 nmol/g tissue versus 9.75 nmol/g tissue; p < 0.01). The placental SOD activity in the study group was significantly higher (p < 0.01) compared to controls (3.57 U/mg protein versus 2.63 U/mg protein). The umbilical cord blood MDA levels in the study group were higher than in normal pregnancies (4.99 nmol/mL, 3.88 nmol/mL; p < 0.05). The activity of SOD in umbilical cord blood was significantly higher (p < 0.001) in patients with nonreassuring fetal status when compared with the control group (11.62 versus 6.95 U/mL). CONCLUSION: Lipid peroxidation products and antioxidant functions were elevated in the umbilical cord blood and placenta of patients having nonreassuring FHR tracings during labor. These findings indicate that lipid peroxidation products in placenta and umbilical cord blood can be used as a possible marker for fetal hypoxia during labor and SOD levels may discriminate acute from chronic hypoxia. Further investigations are needed with large number of series to clarify the variations of lipid peroxidation and antioxidant activity due to acute or chronic fetal hypoxia.     

Lipid and protein peroxidation process and catalase activity in pre-eclamptic placenta

There are some suggestions that free radicals are involved in some dysfunctions observed in preeclampsia. In this study we have examined the antioxidant status of preeclamptic placentas. We have used placentas obtained from normal pregnant women and women with preeclampsia. Lipoperoxidative process was measured by means of Okhawa method. Sedlak method was used to measured the total thiol groups. The catalase activity was measured by means of Pffeifer method. The results show that the catalase activity decreases, the amount of MDA increases and the total amount of thiol groups is smaller in preeclamptic placentas. The level of lipid peroxides in preeclamptic placentas is about 1.8 times higher in comparison with normal placentas. The decreased level of total thiol groups in preeclamptic placentas can be caused by a more intensive process of protein peroxidation. Catalase is less active in preeclamptic placentas. It can be due to lower activity of antioxidant systems or the destruction of antioxidant systems by reactive oxygen species. The results of our experiments confirm lower antioxidant status in preeclamptic placentas and suggest that peroxidative reaction may cause many dysfunctions associated with preeclampsia.