Oxidative stress in diabetic pregnancy: SOD, CAT and GSH-Px activity and lipid peroxidation products.

Diabetic pregnancy is often complicated by a number of pathological conditions among which is increased oxidative stress. This study was conducted to investigate the parameters of oxidative stress in 90 patients divided into the three groups: pregnant women with Type 1 diabetes mellitus, healthy pregnant women and non-pregnant women. In pregnancy groups all parameters were followed in 1st, 2nd and 3rd trimester. Diabetic control was monitored by fasting blood glucose and glycosylated hemoglobin (HbA(1c)) and these values, as well as measured biochemical parameters (urea, creatinine, total cholesterol and uric acid), were appropriate throughout the study. The concentration of TBARS, as a measure of lipid peroxidation, and activity of antioxidant enzymes superoxide dismutase (Cu, Zn-SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) were investigated in hemolysate of erythrocytes. TBARS concentration increased significantly in pregnant women when compared with control group (non-pregnant women), as well as in pregnant diabetics compared with healthy pregnant women. The SOD activity was gradually increased in the group of normal pregnant women vs. non-pregnant group, but decreased significantly in the group of diabetic pregnant women. Catalase activity was significantly increased only in 3rd trimester diabetic pregnant women. Increased lipid peroxidation and reduced antioxidant status, despite good diabetic control, show that pregnant women are exposed to oxidative stress to a greater degree than controls.     

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.     

Evaluation of Oxidative Stress and Antioxidant Defence in Subjects of Preeclampsia

Objectives

To evaluate the parameters of oxidative stress and anti oxidant defense in preeclampsia and thereby find any etiological correlation.

Methods

Study was carried out on pregnant and non pregnant women attending or admitted in the Obstetrics and Gynecology Department of SSG Hospital, Baroda between 1st June 2007 to 31st May 2008. Each serum sample from different groups was evaluated for malondialdehyde (MDA), a product of lipid peroxidation process as a marker for oxidative stress and reduced Glutathione, Superoxide Dismutase, and Catalase for antioxidant enzyme activity and a comparison drawn and analyzed using t-test and χ² test.

Results

The levels of MDA (a lipid peroxidation product) increased significantly in pregnancy compared to non-pregnant females and further significantly increased in preeclampsia compared to normal pregnant females. The superoxide dismutase levels, catalase levels and vit-E levels were found to be increased in preeclamptic females as compared to normal pregnant females.

Conclusion

Preeclampsia is found to be a condition with markedly increased oxidative stress as is evidenced by highly significantly increased levels of MDA, a marker of lipid peroxidation. Levels of antioxidant enzymes, viz. reduced glutathione, superoxide dismutase, catalase and vitamin E have been found to be increased in preeclampsia as compared to normal pregnant females. This may be a compensatory mechanism for handling the increased oxidative stress.     

Lipid and protein oxidation and antioxidant function in women with mild and severe preeclampsia

OBJECT: The aim of this study was to evaluate the lipid and protein oxidation and antioxidant function in preeclampsia patients and in normotensive pregnant women, as well as, to assess an association with the severity of the disease. METHOD: The study was carried out in 30 patients with mild preeclampsia, 30 with severe preeclampsia, and in 50 normotensive pregnant women during the third trimester of pregnancy. Lipid peroxides in serum, placental and decidual tissues and serum protein carbonyls and some of the antioxidants were measured by spectrophotometric methods. One-way analysis of variance, chi-square test and Pearson correlation test were used for the statistical analyses. Logistic regression procedures were used to calculate odds ratios (OR). RESULTS: Lipid peroxides in serum, placenta and decidua basalis and protein carbonyls in serum were significantly increased, and vitamin E and total carotene levels in serum were significantly decreased especially in women with severe preeclampsia compared with mild preeclampsia and controls. A significant correlation was detected between diastolic blood pressure and lipid peroxides in serum, placental and decidual tissues and serum protein carbonyls. Furthermore, there was significant correlation between antioxidant vitamins and lipid and protein oxidation products in severe preeclamptic patients. Also, logistic regression analysis showed that changes in serum, placental and decidual lipid peroxides and serum protein carbonyls, vitamin E and total carotene concentrations were significantly associated with preeclampsia. CONCLUSION: Our findings suggest that lipid and protein oxidation may be an important factor in the pathogenesis of preeclampsia. Since antioxidant vitamins are significantly decreased in both severe and mild preeclamptic pregnants, early supplementation with antioxidants may be beneficial in preeclamptic patients.     

Maternal erythrocyte malondialdehyde level in preeclampsia prediction: a longitudinal study

We aimed to determine the value of maternal erythrocyte malondialdehyde levels in the prediction of preeclampsia. 110 healthy women were included in this prospective study. Maternal erythrocyte malondialdehyde levels were measured at each trimester of pregnancy (10-14, 20-25 and 30-35 gestational weeks). On follow-up, patients were assigned to two groups as normotensive women and preeclamptic patients. Preeclampsia had developed in eight (8.9%) of the 90 pregnant women who completed the study. Preeclamptic patients were diagnosed between 36 and 39 gestational weeks (36.8 +/- 1.0 weeks). Malondialdehyde levels of preeclamptic patients increased significantly in the third trimester (p < 0.05), while there was no difference between values of malondialdehyde in the first and second trimester. Malondialdehyde levels were significantly higher in the patients who developed preeclampsia than in those who did not in the third trimester (p < 0.05). With the use of the receiver operating characteristics (ROC) 35.98 nmol malondialdehyde/gm hemoglobin was found to be a cut-off value predictive for the development of preeclampsia in the third trimester. However, cut-off values in the first and second trimesters could not be found. The sensitivity, specificity, positive and negative predictive values were 89, 75, 29 and 98%, respectively. Preeclampsia risk was found to increase nearly 24 times in values above 35.98 nmol malondialdehyde/ gm hemoglobin. Our results showed that maternal erythrocyte malondialdehyde could predict patients within a few weeks prior to onset of clinical symptoms of preeclampsia in the third trimester. There is no evidence of enhanced early lipid peroxidation in pregnancies with late onset preeclampsia.     

Potential atherogenic roles of lipids, lipoprotein(a) and lipid peroxidation in preeclampsia.

AIMS: To evaluate changes in lipid profile, serum levels of malondialdehyde (MDA) and lipoprotein(a) (Lp(a)) and placental MDA in preeclamptic women, and to evaluate the atherogenic role of these changes in the pathophysiology of pre-eclampsia. METHOD: A cross-sectional study was performed in 20 normal pregnant women, 25 women with mild preeclampsia and 28 women with severe preeclampsia in the third trimester. MDA, which is the endproduct of lipid peroxidation, was measured in placental tissue by the thiobarbituric acid (TBA) method of Ohkawa and colleagues and in serum by the TBA method of Asakawa and Matsushita. Serum lipid levels were measured by with an autoanalyzer, serum apolipoprotein (Apo) A-I and Apo B were measured by nephelometric assay and serum Lp(a) level using a nephelometric agglutination assay method. In preeclamptic and normal pregnant women, multiple comparisons between groups were performed by one-way analysis of variance supplemented with Tukey's HSD post hoc test. The association between placental and serum concentrations among groups was analyzed using the Pearson correlation test. RESULTS: Serum levels of MDA, Lp(a), total cholesterol, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and placental MDA were significantly higher, and high-density lipoprotein cholesterol (HDL-C) and Apo A-I levels were significantly lower, in severely preeclamptic and mildly preeclamptic women than in the normal pregnant women, but no difference was observed in Apo B among groups. Serum level of Lp(a) was positively correlated with body mass index in severely preeclamptic women (r=0.489, p=0.008). A significant positive correlation was also found between serum level of MDA and systolic blood pressure in women with severe preeclampsia (r=0.375, p=0.049). CONCLUSIONS: Our findings suggest that high Lp(a), lipid peroxidation, LDL-C and TG, and low HDL-C and Apo A-I levels, are important risk factors for atherosclerosis among preeclamptic women.     

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 in pregnancy with preeclampsia and diabetes

We studied lipid peroxidation and vitamin E levels in 12 diabetic preeclamptic, 13 nondiabetic preeclamptic, 8 gestational diabetic, 25 normotensive pregnant women, and 25 healthy nonpregnant women. A significant increase in malonaldehyde (MDA) levels was observed in preeclamptic and diabetic preeclamptic women as compared to normotensive pregnant and healthy controls (p<0.001). An increase in MDA levels was observed in gestational diabetics, but the difference was not statistically significant. Likewise, a significant fall in vitamin E levels was noted in preeclamptic and diabetic preeclamptic groups as compared to controls (p<0.001). Gestational diabetics had a slight decrease in vitamin E levels relative to controls. These findings suggest that lipid peroxidation plays a role in the pathogenesis of preeclampsia.     

Estimation of oxidative stress and its correlation with uterine arteries Doppler velocimetry in women with preeclampsia

OBJECTIVES: Estimation of oxidative stress through the measurement of lipid peroxides and malondialdehyde serum concentration as well as serum antioxidants level expressed by total antioxidants status and its correlation with Doppler velocimetry in women with preeclampsia. MATERIAL AND METHODS: Thirty four patients with preeclampsia at third trimester of gestation: 19 with the mild form and 15 with the severe form of the disease, 21 women with uncomplicated pregnancy at third trimester of gestation served as a control group. Colorimetric methods were used to estimate lipid peroxides, malondialdehyde and antioxidants serum level. In each patient Pulsatility Index and Uterine Artery Score in uterine arteries was measured. RESULTS: Serum concentration of lipid peroxides and malondialdehyde was the highest in patients with severe preeclampsia, but the statistical difference concerned only lipid peroxides level which was significantly higher in this group than in women with mild form of the disease and in the control group. Pulsatility index Uterine Artery Score values were significantly higher in women with severe preeclampsia in comparison to two other groups of patients. Lipid peroxides level significantly positively correlated with Pulsatility Index and Uterine Artery Score values in the whole studied population. CONCLUSIONS: Only severe form of preeclampsia is associated with oxidative stress which impaired placenta perfusion expressed by the increase of uterine arteries resistance.     

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.     

Evaluation of the macula,retinal nerve fiber layer and choroid in preeclampsia,healthy pregnant and healthy non-pregnant women using spectral-domain optical coherence tomography

Objective: To evaluate the macular, retinal nerve fiber layer (RNFL) and choroidal thickness alterations by using spectral-domain optical coherence tomography (SD-OCT) in preeclampsia and compare with healthy pregnant and healthy non-pregnant controls. Method: The study population included healthy pregnant control group (n: 25), healthy non-pregnant control group (n: 26) and study group with preeclampsia (n: 27). Retinal thickness parameters were measured by SD-OCT. Results: There was a statistically significant difference among all of the groups for choroidal thickness (p?p?p?p?=?0.004). Conclusions: This study revealed that choroidal thickness measured using SD-OCT increased in women with preeclampsia and healthy pregnant women but the increase in choroidal thickness in preeclampsia was lower than the healthy pregnant controls. This lower rise in choroidal thickness can be generally attributed to the markedly increased systemic vascular vasospasm secondary to preeclampsia.     

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.     

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.     

Sera antioxidant activity in uncomplicated and preeclamptic pregnancies.

Uncontrolled lipid peroxidation may play an important role in the pathophysiology of preeclampsia by causing vascular endothelial cell dysfunction. Sera contain antioxidant mechanisms that serve to control lipid peroxidation. We tested the hypothesis that the sera antioxidant protective mechanisms are diminished in women with preeclampsia. Blood samples were collected within 24 hours of delivery (pre-delivery) and by 24 hours postpartum (post-delivery) from women with preeclampsia (N = 8) and from matched controls with uncomplicated pregnancies (N = 8). Antioxidant activity was determined by the ability of sera to inhibit autoxidation of a standardized brain homogenate. Lipid peroxidation of both brain homogenate and sera was analyzed by high-pressure liquid chromatography using the amount of malondialdehyde present as an indicator of peroxidation. Pre-delivery sera from women with preeclamptic pregnancies had one-half the antioxidant activity of sera from women with uncomplicated pregnancies (42 versus 90%; P less than .01). Malondialdehyde values alone were not significantly different between the groups in either the pre-delivery or post-delivery samples. When using a ratio to evaluate the relative balance between lipid peroxidation and antioxidant activity, pre-delivery samples from women with preeclampsia had over a twofold increase in this ratio compared with samples from uncomplicated pregnancies. In conclusion, in contrast to women with uncomplicated pregnancies, women with preeclampsia have antioxidant activity that is markedly reduced by late gestation. For women with preeclampsia, this may result in a greater potential for endothelial oxidative damage.     

Butyrylcholinesterase (BChE) activity is associated with the risk of preeclampsia: influence on lipid and lipoprotein metabolism and oxidative stress

Abstract

Objective: To determine the butyrylcholinesterase (BChE) activity and phenotypes in preeclampsia and its possible association with lipid and lipoprotein metabolism and oxidative stress in preeclamptic women.

Methods: In a case–control study, 101 pregnant women with normal pregnancy and 198 women with preeclampsia from Western Iran were studied. The serum BChE activity and phenotypes were measured using spectrophotometric method. The apolipoprotein E (APOE) genotypes were identified using PCR-RFLP. The serum malondialdehyde (MDA) level and total antioxidant capacity (TAC) were determined by HPLC and commercial kits, respectively.

Results: The BChE activity and the frequency of non-usual BChE phenotype in preeclamptic women were significantly lower and higher, respectively compared to controls. There was a higher BChE activity in the presence of APOE ε3ε4 compared to ε3ε3 genotype in preeclamptic women. In addition, there were significant positive correlations between BChE activity and the levels of low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, total cholesterol (TC) and TAC. However, there was a negative but significant correlation between BChE activity and MDA level.

Conclusions: Our study for the first time indicated that BChE activity might be involved in the pathogenesis of preeclampsia through influence on lipid and lipoprotein metabolism and oxidative stress.     

Increased endothelial monocyte chemoattractant protein-1 and interleukin-8 in preeclampsia

OBJECTIVE: To test the hypothesis that preeclampsia is associated with increased endothelial cell chemokine production of monocyte chemoattractant protein-1 and interleukin-8 necessary for monocyte recruitment to the vascular endothelium. METHODS: Plasma was collected from women with severe preeclampsia and normal pregnant women at term and measured for monocyte chemoattractant protein-1, interleukin-8, and lipid peroxide levels by enzyme-linked immunosorbent assays and malondialdehyde assays. Human umbilical vein endothelial cells were cultured with 5% plasma from normal or preeclamptic patients and the media assayed for monocyte chemoattractant protein-1 and interleukin-8 production. RESULTS: In women with severe preeclampsia, plasma levels of monocyte chemoattractant protein-1, interleukin-8, and lipid peroxides were elevated (1.5-fold, 2.5-fold, and 4.5-fold higher, respectively) compared with normal pregnant women. Human umbilical vein endothelial cells cultured with plasma from preeclamptic women significantly increased the production of both monocyte chemoattractant protein-1 (2.3-fold) and interleukin-8 (1.5-fold) compared with plasma from normal pregnant women. Monocyte chemoattractant protein-1 and interleukin-8 production was decreased by the antioxidant vitamin E in human umbilical vein endothelial cells treated with preeclamptic plasma, suggesting that the production of these cytokines may be regulated by signaling mechanisms sensitive to oxidative stress. CONCLUSION: These findings support the hypothesis that circulating factors in the plasma of women with preeclampsia activate endothelial cell monocyte chemoattractant protein-1 and interleukin-8 production, and although not directly examined in this study, may increase monocyte adherence to the vascular endothelium.     

Low plasma levels of oxidized low density lipoprotein in preeclampsia

BACKGROUND: Markers of lipid peroxidation are commonly used to assess oxidative stress in preeclampsia. The aim of this study was to assess the concentration of oxidized low density lipoprotein (oxLDL), a novel marker for lipid peroxidation, and that of the thiobarbituric acid reactive substances (TBARS) in the pathogenesis of severe preeclampsia and to investigate the influence of gestational age on these parameters. METHOD: Plasma levels of oxLDL and TBARS were assayed in women with severe preeclampsia (n = 40), normotensive pregnant controls matched for gestational age (n = 24) and normotensive pregnant controls at full term (n = 16). RESULTS: Women with preeclampsia showed lower oxLDL levels (mean +/- SE) than matched controls (181 +/- 12 vs. 219 +/- 14; p = 0.027), whereas no differences were found for the TBARS concentration (3.8 +/- 0.6 vs. 3.7 +/- 0.4). When women with preeclampsia were compared to control women at full term, TBARS were elevated (3.8 +/- 0.6 vs. 1.5 +/- 0.2; p = 0.01). However, in women with normotensive pregnancy TBARS were also lower in full-term control pregnancy compared to early third-trimester values (p < 0.0001). CONCLUSION: Plasma TBARS decreased during the third trimester of pregnancy, underlining the importance of matching for gestational age when studying markers of lipid peroxidation in pregnant women. Women with preeclampsia had lower plasma levels of oxLDL compared to gestational age-matched controls, indicating that oxLDL could be a marker for preeclampsia.     

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.     

Lipid peroxidation, antioxidant defense, status of trace metals and leptin levels in preeclampsia

OBJECTIVE: To investigate the changes in enzyme activities of erythrocyte superoxide dismutase (SOD), catalase, and placental glutathione peroxidase (GSH-Px), and analyze the levels of serum malondialdehyde (MDA), copper (Cu), zinc (Zn), selenium (Se), leptin and placental MDA and glutathione (GSH). STUDY DESIGN: Cross-sectional prospective study consisting of 32 preeclamptic (PE) pregnant, 25 non-pregnant (NP) women, 28 healthy pregnant (HP) women. Levels of lipid peroxides in serum and placenta, and activities of SOD, catalase in erythrocyte and placental GSH level, placental GSH-Px activity were measured by spectrophotometric methods. Serum levels of Cu, Zn, Se measured by atomic absorption spectrophotometry. Serum levels of leptin was measured by enzyme immunoassay by using the Cayman chemical kit. One-way analysis of variance and post hoc Tukey-HSD test and Pearson correlation test were used for the statistical analyses. RESULTS: Serum levels of MDA, Cu, Leptin were markedly higher (P < 0.001); and serum level of Se was markedly lower (P < 0.001) in PE women compared with HP women and NP women. Also, placental MDA level was higher (P < 0.001) and placental GSH-Px activity was lower in PE women compared with HP women. In preeclamptic women erythrocyte catalase activity was markedly increased (P < 0.001), while erythrocyte SOD activity was markedly decreased (P < 0.001) compared to HP women and NP women. Placental GSH level was decreased compared to HP women (P < 0.001). Serum level of Zn was markedly decreased compared to NP women (P < 0.001) but no significant difference was observed in PE pregnant when compared with HP women (P > 0.05). Placental MDA level in PE women had significant negative correlation with serum Se level (r = -0.353, P < 0.05). A negative correlation was found between erythrocyte catalase activity with birth weight (r = -0.528, P < 0.001). Also, there were a significant negative correlation between serum levels of Cu and Se in the preeclamptic women (r = -0.407, P < 0.05). CONCLUSION: Our data demonstrate that elevation of lipid peroxides together with impaired antioxidant defense mechanisms and status of trace metals and the presence of possible interrelationship and crosstalk between those parameters may be related at least partly to the pathogenesis of preeclampsia. Additionally, lipid peroxides and blood oxidative imbalance could be part of the cytotoxic mechanisms leading to endothelial cell injury.     

Granulocyte superoxide anion production and regulation by plasma factors in normal and preeclamptic pregnancy

Data on the respiratory burst activity of granulocytes from healthy and preeclamptic women have remained contradictory. To investigate the role of reactive oxygen species in the etiology of preeclampsia we measured superoxide anion generation by granulocytes from non-pregnant, healthy, and preeclamptic women. We also examined the reciprocal effects of heat-inactivated and non-inactivated plasma on superoxide production. Superoxide generation was measured by ferricytochrome-c reduction. Superoxide production induced by either phorbol-12,13-dibutirate or N-formyl-methionyl-leucyl-phenylalanine was significantly decreased in granulocytes from normal pregnant women compared with non-pregnant and preeclamptic women. The phorbol-12,13-dibutirate-induced superoxide generation by granulocytes from non-pregnant and preeclamptic women was significantly inhibited by plasma from healthy pregnant women. The N-formyl-methionyl-leucyl-phenylalanine-stimulated superoxide production by granulocytes from non-pregnant and preeclamptic women was suppressed only by non-inactivated plasma, not heat-inactivated plasma from healthy pregnant women. Plasma from preeclamptic women did not influence the phorbol-12,13-dibutirate- and N-formyl-methionyl-leucyl-phenylalanine-induced superoxide production by control granulocytes. The phorbol-12,13-dibutirate-induced superoxide generation by granulocytes from healthy pregnant women was significantly increased by the effect of plasma from non-pregnant and preeclamptic women, but when stimulating with N-formyl-methionyl-leucyl-phenylalanine only non-inactivated plasma caused the same enhancement. These data indicate that reduced superoxide generation in normal pregnancy may be caused by maternal immunosuppressive factors present in plasma. The failure to reduce superoxide production in preeclampsia may be partly responsible for the endothelial dysfunction characteristic of that condition.