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ABSTRACT: Background. To study the possible involvement of an (im)balance between oxidants and antioxidants in pre-eclampsia concentrations of intra- and extracellular blood antioxidants in women with uncomplicated and hypertensive pregnancies, they were studied preconceptionally and throughout pregnancy. Methods. In uncomplicated pregnancies (n=19) and hypertensive pregnancies (n=6) concentrations of whole blood and plasma thiols, plasma vitamins E and C, hemoglobin, and hematocrit were assessed at preconception, 6, 10, 20, and 37 weeks of gestational age, as well as six weeks postpartum. A repeated mixed model was used for statistical analysis. Results. Vitamin C and most whole blood and plasma thiol concentrations decreased during pregnancy, while vitamin E, whole blood oxidized cysteinyl-glycine and the ratio of free to oxidized homocysteine revealed a linear increase during pregnancy. Postpartum plasma cysteine and vitamin C levels and the ratio of free to oxidized levels of cysteine, cysteinyl-glycine, and glutathione were significantly (p<0.05) lower as compared to preconceptional levels, whereas whole blood oxidized cysteine, cysteinyl-glycine and glutathione levels, and whole blood and plasma homocysteine levels were significantly (p<0.05) higher six weeks after delivery. Plasma cysteine and homocysteine, and whole blood oxidized cysteine and homocysteine levels were significantly (p<0.05) higher at 37 weeks of gestational age in the hypertensive group compared to those in the uncomplicated group. There were no other differences between the hypertensive and uncomplicated groups. Conclusion. In normal pregnancy there seems a balance between antioxidant and oxidant concentrations despite modest oxidative stress. In mildly hypertensive pregnancies a marginal imbalance may occur.
Acta Obstetricia Et Gynecologica Scandinavica 12/2010; 85(2):148 - 155. · 1.77 Impact Factor
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ABSTRACT: Glutathione, an intracellular tripeptide, functions in the protection of cells against free radicals and toxins of endogenous and exogenous origin. To maintain the intracellular redox status in presence of reactive oxygen species, glutathione (GSH) and other thiols are oxidized. The oxidative status of thiols is reflected by the free-to-oxidized ratio and is a real-time measure for oxidative stress. Previously, we have reported abnormal ratios for the thiols cysteine (Cys), homocysteine (Hcy) and cysteinylglycine (CysGly) in women with pre-eclampsia. The aims of this study were to confirm our previous findings in a different case-control cohort and more importantly to determine whether these differences persist postpartum.
At onset of disease and at 6-8 weeks postpartum we analyzed whole blood of 41 women with pre-eclampsia and of 31 women with normotensive pregnancies for the free-to-oxidized ratio of thiols by the assessment of free and oxidized thiol levels using high performance liquid chromatography. Differences between values were determined using either the paired t-test (antepartum versus postpartum) or the t-test (pre-eclampsia versus normotensive pregnancy).
Antepartum levels of free GSH as well as the free-to-oxidized ratios of Hcy were lower in pre-eclampsia and normotensive pregnancy when compared with corresponding postpartum values (P<0.0001 and P<0.01, respectively). Moreover, the free-to-oxidized ratio for Hcy was significantly lowered in pre-eclamptic compared with normotensive women, during as well as after pregnancy (both P< or =0.01).
The data suggest that pregnancy is a state of higher oxidative stress when compared to the postpartum period. In women with pre-eclampsia, oxidative stress is higher and persists in the postpartum period.
European Journal of Obstetrics & Gynecology and Reproductive Biology 05/2008; 138(1):39-44. · 1.97 Impact Factor
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ABSTRACT: Preeclampsia is a common pregnancy-specific syndrome that is diagnosed by the appearance of both increased blood pressure and proteinuria. Preeclampsia is associated with significant fetal and maternal morbidity and mortality. Although the etiology of preeclampsia is unknown, it is evident that abnormal placentation and trophoblast metabolism plays an important role. We therefore analyzed, identified, and verified specific proteins of villous trophoblast and villous stroma in small numbers of microdissected cells (approximately 125 cells) from seven placentas of women with pregnancies complicated by preeclampsia (cases) and seven uncomplicated pregnancies (controls). Tryptic peptide profiling by MALDI-TOF MS was used for comparison and identification of significantly expressed peptides. The data were analyzed by ClinProTools (Bruker Daltonics) and by principal component analysis. Subsequently, a subset of placental tissues were homogenized and separated on a NanoLC system to obtain sequencing information (MS/MS spectra). We identified specific peptide patterns in the different cell types: villous stroma and trophoblast cells and differences in these cells of placentas from women with pregnancies complicated by early compared to late onset preeclampsia (<34 and >34 wk gestation, respectively) and controls. Principal component analysis revealed significant differences between the groups. The comparison with placental tissue after preterm delivery with unknown cause revealed that placental peptide patterns in early onset preeclampsia could not be explained by preterm delivery per se. Subsequently, specific, discriminating proteins for early onset preeclampsia compared to controls were identified including calcyclin, surfeit locus protein, and choriomammotropin A precursor. The expression of calcyclin was verified in early onset preeclamptic placental sections by immunohistochemistry. These data suggest that in early onset preeclampsia trophoblastic choriomammotropin regulation is abnormal, possibly through abnormal calcyclin expression and regulation.
Proteomics. Clinical applications 03/2007; 1(3):325-35. · 1.97 Impact Factor
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ABSTRACT: To stabilise the disease process in women with early onset severe preeclampsia and/or HELLP syndrome by enhancing maternal antioxidants effects of glutathione.
In a randomised, double-blind, placebo-controlled trial, women with severe preeclampsia and/or HELLP syndrome received oral N-acetylcysteine. Primary outcome measures were disease stabilisation expressed as treatment-to-delivery interval and biochemical assessment of glutathione and parameters of oxidative stress. Secondary outcome measures were maternal complications, rate of caesarean section, stay at intensive care unit, postpartum hospital stay and neonatal morbidity and mortality. Analyses were done by intention-to-treat using Wilcoxon's two-sample test and regression analysis.
Median treatment-to-delivery interval was not significantly different between the N-acetylcysteine and placebo group. The whole blood and plasma levels of glutathione and other thiols were not affected by N-acetylcysteine administration, except for plasma homocysteine concentrations, which were lower in the N-acetylcysteine group. There were no differences found in maternal nor neonatal secondary outcome measures between both groups.
Oral N-acetylcysteine administration does not stabilise the disease process of early onset severe preeclampsia and/or HELLP syndrome.
European Journal of Obstetrics & Gynecology and Reproductive Biology 08/2006; 127(1):61-7. · 1.97 Impact Factor
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ABSTRACT: To determine the blood concentrations of myo-inositol, glucose and zinc before, during and after normal pregnancy.
Preconceptionally, at 6, 10, 20, 30 and 37 weeks amenorrhea, and 6 weeks after delivery, blood samples of 18 nulliparae and 19 multiparae were obtained and concentrations of serum inositol and glucose, and red blood cell zinc were determined. The data were analyzed using a linear mixed model.
The preconceptional mean (S.E.M.) inositol concentration of 21.7 (1.03) micromol/L was comparable to the concentrations at 6 and 37 weeks amenorrhea, 22.2 (1.03) micromol/L, and 19.9 (1.10) micromol/L, respectively. However, the inositol concentrations at 10 and 20 weeks amenorrhea and post partum were significantly lower than the preconceptional inositol concentration, p<0.05. The preconceptional mean (S.E.M.) glucose concentration of 3.9 (1.03) mmol/L was comparable to the concentration at 6 and 10 weeks amenorrhea, 3.9 (1.04) mmol/L and 3.8 (1.04) mmol/L respectively. Also at 20, 30 and 37 weeks amenorrhea and after delivery the glucose concentration was significantly lower than the preconceptional glucose concentration, p<0.05. Preconceptional red blood cell zinc concentrations were comparable to concentrations at 6, 10 and 20 weeks amenorrhea. At 30 and 37 weeks amenorrhea and post partum the zinc concentrations were significantly higher than in the preconceptional period (p<0.01).
The concentrations of inositol, glucose and zinc significantly change during pregnancy. However, the preconceptional blood concentrations reflect the concentrations determined in the first pregnancy trimester rather well, which is important information to be used in future studies into the role of inositol, glucose and zinc in reproductive disorders.
European Journal of Obstetrics & Gynecology and Reproductive Biology 07/2006; 127(1):50-5. · 1.97 Impact Factor
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ABSTRACT: To study the possible involvement of an (im)balance between oxidants and antioxidants in pre-eclampsia concentrations of intra- and extracellular blood antioxidants in women with uncomplicated and hypertensive pregnancies, they were studied preconceptionally and throughout pregnancy.
In uncomplicated pregnancies (n = 19) and hypertensive pregnancies (n = 6) concentrations of whole blood and plasma thiols, plasma vitamins/E and C, hemoglobin, and hematocrit were assessed at preconception, 6, 10, 20, and 37 weeks of gestational age, as well as six weeks postpartum. A repeated mixed model was used for statistical analysis.
Vitamin C and most whole blood and plasma thiol concentrations decreased during pregnancy, while vitamin E, whole blood oxidized cysteinyl-glycine and the ratio of free to oxidized homocysteine revealed a linear increase during pregnancy. Postpartum plasma cysteine and vitamin C levels and the ratio of free to oxidized levels of cysteine, cysteinyl-glycine, and glutathione were significantly (p <0.05) lower as compared to preconceptional levels, whereas whole blood oxidized cysteine, cysteinyl-glycine and glutathione levels, and whole blood and plasma homocysteine levels were significantly (p <0.05) higher six weeks after delivery. Plasma cysteine and homocysteine, and whole blood oxidized cysteine and homocysteine levels were significantly (p <0.05) higher at 37 weeks of gestational age in the hypertensive group compared to those in the uncomplicated group. There were no other differences between the hypertensive and uncomplicated groups.
In normal pregnancy there seems a balance between antioxidant and oxidant concentrations despite modest oxidative stress. In mildly hypertensive pregnancies a marginal imbalance may occur.
Acta Obstetricia Et Gynecologica Scandinavica 02/2006; 85(2):148-55. · 1.77 Impact Factor
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ABSTRACT: This study was undertaken to determine whether the N-acetyltransferase (NAT) phenotype contributes to the susceptibility for the development of preeclampsia.
The NAT acetylator status was determined by measuring urinary caffeine metabolites in 134 nonpregnant women with a history of preeclampsia and in 109 control women with uncomplicated pregnancy. The chi(2) and logistic regression analyses were used for statistical evaluation of differences in acetylator status.
Significantly more fast acetylators were found among the women with a history of preeclampsia (46.3%) than among the controls (25.4%). Fast acetylators showed an odds ratio of 2.5 (95% CI 1.4-4.3) for preeclampsia. No differences in the acetylator status were found between women with a history of preeclampsia only and those with the HELLP syndrome as well.
The fast NAT acetylator status, which may result in altered NAT detoxification capacity, is associated with preeclampsia.
American Journal of Obstetrics and Gynecology 10/2005; 193(3 Pt 1):797-802. · 3.47 Impact Factor
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ABSTRACT: To evaluate the physical and mental health of women with a history of severe preeclampsia.
In a historical cohort study 131 former patients with a history of severe preeclampsia and 127 control patients received questionnaires about experienced physical and mental complaints after delivery. At a follow-up visit blood pressure, body mass index, and proteinuria were measured and venous blood was drawn.
Former patients experienced significantly (p < 0.001) more frequent problems of headache (31% vs. 2%), right upper quadrant pain (16% vs. 1%), visual disturbances (21% vs. 1%), tiredness (66% vs. 27%), subjective loss of concentration (37% vs. 16%), and mental health (37% vs. 6%) compared with controls. When present, these health problems, except for tiredness, lasted significantly more often beyond six months postpartum compared to controls. Admittance to the intensive care unit was associated with headache, and subjective loss of memory and concentration over a longer period of time. The risk of recurrence of severe preeclampsia was a subject of concern in 20% of former patients. At follow-up, systolic and diastolic blood pressures were significantly higher (p < 0.001) among former patients.
Patients with a history of severe preeclampsia more frequently reported physical and mental complaints, also during a longer period of time.
Journal of Maternal-Fetal and Neonatal Medicine 07/2005; 18(1):39-45. · 1.50 Impact Factor
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ABSTRACT: To analyse the post-partum concentrations of intra- and extra-cellular blood antioxidants in women with uncomplicated pregnancies.
Whole blood and plasma thiols, plasma vitamin E and C, serum cholesterol and triglyceride, ferric reducing ability of plasma (FRAP) concentrations were compared between women delivered by caesarean section (n=17) or spontaneous delivery (n=10). A repeated mixed model was used for statistical analysis.
The majority of whole blood thiols increased significantly in both groups the first days post-partum. However, within the caesarean group free cysteine, oxidised cysteine, homocysteine and glutathione and plasma cysteine and homocysteine levels dropped significantly after 24 h, while FRAP levels peaked significantly in this group. Plasma vitamin E levels decreased significantly in both groups within 24 to 48 h after delivery. Independent of the way of delivery whole blood and plasma thiols were significantly increased and vitamin E levels were significantly decreased 3 months post-partum while plasma vitamin C levels and FRAP were unchanged compared to ante-partum levels.
Decreased plasma vitamin E levels shortly post-partum are associated with decreased lipid peroxidation. The 24 h post-partum drop of some plasma and whole blood thiols in the caesarean group may be due to prolonged fasting.
Free Radical Research 02/2005; 39(1):95-103. · 2.88 Impact Factor
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ABSTRACT: 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.
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).
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).
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.
Acta Obstetricia Et Gynecologica Scandinavica 12/2004; 83(12):1173-7. · 1.77 Impact Factor
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ABSTRACT: Preeclampsia is associated with an imbalance between oxidants and antioxidants, resulting in reduced effects of the endothelium-derived, relaxing-factor nitric oxide (NO). Antioxidants, like N-acetylcysteine (NAC), remove reactive oxygen species, resulting in an improvement of endothelial function. We aimed to investigate the effect of NAC on the NO-pathway in the human fetoplacental circulation in preeclampsia and control pregnancies.
The NO-pathway was investigated by use of the NO-synthase inhibitor L-NAME in an ex vivo cotyledon perfusion model.
At baseline, fetoplacental arterial pressure was comparable in preeclamptic pregnancies (n=8) and control pregnancies (n=8), and increased dose-dependently after L-NAME. The maximal L-NAME-induced rise in fetoplacental arterial pressure was attenuated in preeclamptic versus control pregnancies (20.8 +/- 2.0 mm Hg vs 36.7 +/- 3.5 mm Hg, P<.05). Addition of NAC increased the L-NAME-induced rise in fetoplacental arterial pressure to 36.4 +/- 3.4 mm Hg in preeclampsia pregnancies (P<.05) and to 49.2 +/- 2.6 mm Hg in control pregnancies (P<.05).
Preeclampsia is associated with a dysfunction of the NO-pathway. N-acetylcysteine increases NO-mediated effects in the fetoplacental circulation in preeclamptic placentas as well as in healthy control placentas.
American Journal of Obstetrics and Gynecology 07/2004; 191(1):328-33. · 3.47 Impact Factor
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ABSTRACT: To investigate a possible mechanism that could lead to the subsequent development of cardiovascular diseases (CVD) in women with a history of severe pre-eclampsia.
Case-control study.
University Medical Centre Nijmegen, The Netherlands.
Non-pregnant women with a history of severe pre-eclampsia (n= 131) and women with an uncomplicated obstetric history (n= 94).
Total plasma levels of cysteine (tCys), homocysteine (tHcy), cysteinylglycine (tCysGly) and glutathione (tGSH), the free-to-oxidised ratio of these thiols in whole blood, the glucose-6-phosphate dehydrogenase (G6PDH) enzyme activity and antioxidant capacity were assessed at least 6 months following last pregnancy.
Oxidative stress and antioxidant status.
Women with a history of severe pre-eclampsia showed higher levels (mean [SD]) of tHcy (13.1 [5.0] versus 11.5 [4.8] micromol/L; P= 0.018) and tCysGly (37.5 [5.6] versus 34.0 [5.8] micromol/L; P= 0.0001) compared with controls, whereas tCys was lower (232 [31] versus 242 [39]; P= 0.029). The lower free-to-oxidised ratio of homocysteine (2.3 [0.8] versus 2.9 [1.0], P= 0.0001) among women with a history of severe pre-eclampsia as compared with control subjects might indicate a higher oxidant status for homocysteine. Previous severe pre-eclamptic patients had also a higher antioxidant capacity as compared with controls (0.79 [0.14] versus 0.74 [0.11] mmol Fe2+/L, P= 0.002).
Since women with a history of severe pre-eclampsia showed elevated total homocysteine levels, which is an independent risk factor for CVD, and higher oxidised homocysteine levels in whole blood, these women may have an enhanced risk for the subsequent development of cardiovascular-related problems in later life.
BJOG An International Journal of Obstetrics & Gynaecology 04/2004; 111(3):207-12. · 3.41 Impact Factor
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ABSTRACT: Objective To investigate a possible mechanism that could lead to the subsequent development of cardiovascular diseases (CVD) in women with a history of severe pre-eclampsia.Design Case–control study.Setting University Medical Centre Nijmegen, The Netherlands.Sample Non-pregnant women with a history of severe pre-eclampsia (n= 131) and women with an uncomplicated obstetric history (n= 94).Methods Total plasma levels of cysteine (tCys), homocysteine (tHcy), cysteinylglycine (tCysGly) and glutathione (tGSH), the free-to-oxidised ratio of these thiols in whole blood, the glucose-6-phosphate dehydrogenase (G6PDH) enzyme activity and antioxidant capacity were assessed at least 6 months following last pregnancy.Main outcome measure Oxidative stress and antioxidant status.Results Women with a history of severe pre-eclampsia showed higher levels (mean [SD]) of tHcy (13.1 [5.0] versus 11.5 [4.8] μmol/L; P= 0.018) and tCysGly (37.5 [5.6] versus 34.0 [5.8] μmol/L; P= 0.0001) compared with controls, whereas tCys was lower (232 [31] versus 242 [39]; P= 0.029). The lower free-to-oxidised ratio of homocysteine (2.3 [0.8] versus 2.9 [1.0], P= 0.0001) among women with a history of severe pre-eclampsia as compared with control subjects might indicate a higher oxidant status for homocysteine. Previous severe pre-eclamptic patients had also a higher antioxidant capacity as compared with controls (0.79 [0.14] versus 0.74 [0.11] mmol Fe2+/L, P= 0.002).Conclusion Since women with a history of severe pre-eclampsia showed elevated total homocysteine levels, which is an independent risk factor for CVD, and higher oxidised homocysteine levels in whole blood, these women may have an enhanced risk for the subsequent development of cardiovascular-related problems in later life.
BJOG An International Journal of Obstetrics & Gynaecology 02/2004; 111(3):207 - 212. · 3.41 Impact Factor
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Hepatology 12/2003; 33(3):765 - 765. · 11.66 Impact Factor
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ABSTRACT: Methionine loading seems to be accompanied by increased oxidative stress and damage. However, it is not known how this oxidative stress is generated. We performed the present crossover study to further elucidate the effects of methionine loading on oxidative stress in the blood of healthy volunteers, and to examine possible preventative effects of N -acetylcysteine (NAC) administration. A total of 18 healthy subjects were given two oral methionine loads of 100 mg/kg body weight, 4 weeks apart, one without NAC (Met group), and one in combination with supplementation with 2x900 mg doses of NAC (Met+NAC group). Blood samples were collected before and 2, 4, 8 and 24 h after methionine loading for measurements of thiol levels, protein carbonyls, lipid peroxidation, cellular fibronectin and ferric reducing ability of plasma (FRAP; i.e. antioxidant capacity). After methionine loading, whole-blood levels of free and oxidized cysteine and homocysteine were increased in both groups. Furthermore, the total plasma levels of homocysteine were higher, whereas those of cysteine were lower, after methionine loading in both groups. Lower levels of oxidized homocysteine and a higher free/oxidized ratio were found in the Met+NAC group compared with the Met group. Although the antioxidant capacity decreased after methionine loading, no major changes over time were found for protein carbonyls or cellular fibronectin in either group. Our results suggest that methionine loading may initiate the generation of reactive oxygen species by the (auto)-oxidation of homocysteine. In addition, supplementation with NAC seems to be able to partially prevent excessive increases in the levels of homocysteine in plasma and of oxidized homocysteine in whole blood, and might thereby contribute to the prevention of oxidative stress.
Clinical Science 09/2003; 105(2):173-80. · 4.61 Impact Factor
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ABSTRACT: Glutathione plays an important role in quenching reactive oxygen species, resulting in oxidation of glutathione, which in times of prolonged oxidative stress may be excreted from the erythrocyte. We investigated arterial and venous umbilical cord levels of glutathione in neonates born by vaginal delivery (n = 140) or cesarean section (n = 38). In a subset of neonates who were delivered vaginally maternal levels were assessed in parallel (n = 14). Median (5th-95th percentile) glutathione levels in venous and arterial umbilical samples were higher after vaginal delivery as compared to cesarean section, 2.7 (0.9-7.3) versus 2.0 (0.6-11.5; P < 0.03) and 3.5 (0.6-22.7) versus 2.3 (0.7-24.3) micromol/L (P < 0.02), respectively. Maternal glutathione levels were higher, 7.8 (4.3-10.6) micromol/L, than corresponding venous (P < 0.001) or arterial (P < 0.02) umbilical levels. These results suggest that vaginal delivery is associated with more oxidative stress than delivery by cesarean section.
Journal of Perinatal Medicine 02/2003; 31(6):520-2. · 1.70 Impact Factor
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ABSTRACT: The purpose of this study was to evaluate the plasminogen activator system in maternal and umbilical cord plasma in patients with severe preeclampsia compared with control subjects with normotensive pregnancies.
Maternal blood was sampled from 42 patients at a median gestational age of 32 weeks; after delivery, arterial and venous umbilical cord blood was sampled from 37 and 36 of these patients, respectively. Maternal blood from women with uncomplicated pregnancies was sampled at the gestational age of 32 weeks (n = 18, group I), and umbilical cord blood was sampled after premature deliveries of normotensive pregnancies (n = 5, group II). Data were analyzed with the use of Mann-Whitney U tests.
Patients had significantly higher tissue plasminogen activator (P <.01) and unchanged urokinase plasminogen activator plasma levels compared with control subjects at 32 weeks of gestation; lower plasminogen activator inhibitor type 2 (P < 0.01) and no different plasminogen activator inhibitor type 1 concentrations were observed compared to control subjects at 32 weeks of gestation. In the arterial and venous umbilical cord plasma of patients, plasminogen activator inhibitor type 1 levels were significantly higher(P <.01) compared with control subjects at 32 weeks of gestation, although urokinase plasminogen activator levels in arterial and venous umbilical cord plasma (P < 0.01) were significantly lower.
Lower plasminogen activator inhibitor type 2 levels are associated with placental insufficiency, and higher tissue plasminogen activator levels are associated with endothelial dysfunction in patients with severe preeclampsia. The higher plasminogen activator inhibitor type 1 levels and lower urokinase plasminogen activator levels in umbilical cord of these patients are suggestive of decreased fibrinolysis in the fetal circulation.
American Journal of Obstetrics and Gynecology 10/2002; 187(4):1019-25. · 3.47 Impact Factor
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ABSTRACT: Oral N-acetylcysteine supplementation in nine young healthy females induced a quick and highly significant decrease in plasma homocysteine levels and an increase in whole blood concentration of the antioxidant glutathione. N-acetylcysteine impresses as an efficient drug in lowering homocysteine concentration and might be beneficial for individuals with hyperhomocysteinemia who are at increased risk of cardiovascular disease.
Clinical Chemistry and Laboratory Medicine 06/2002; 40(5):496-8. · 2.15 Impact Factor
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ABSTRACT: Objective: To measure levels of oxidized and free thiols in whole blood of normotensive pregnant and preeclamptic women and evaluate the role of oxidative stress.
Methods: We measured whole blood oxidized and free levels of cysteine, homocysteine, cysteinylglycine, and glutathione by high performance liquid chromatography in women with normotensive pregnancies (n = 50), preeclampsia (n = 29), and preeclampsia complicated by the hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome (n = 16).
Results: Oxidized and free levels (median [range], μmol/L) of cysteine and homocysteine were higher in women with preeclampsia than normotensive pregnancies (45 [27-81] versus 29 [9-91], P < .001, and 98 [57-193] versus 69 [33-215], P < .001; 0.8 [0.2-4.4] versus 0.4 [0.01-1.6], P < .001, and 2.1 [0.7-9.4] versus 1.2 [0.2-21.2], P < .01; respectively). The ratios of free to oxidized cysteine, homocysteine, and cysteinylglycine were lower in preeclampsia than normotensive pregnancy (2.2 [1.3-3.0] versus 2.4 [1.7-4.3], P < .001; 2.3 [0.5-5.4] versus 2.9 [1.1-24], P < .001; 4.1 [2.3-11.6] versus 5.4 [2.6-24.3], P < .02, respectively), indicating a shift in favor of the oxidized form of those thiols. In HELLP syndrome, levels of oxidized and free cysteine and levels of oxidized homocysteine were higher than normal (44 [33-63] versus 29 [9-91], P < .001, and 102 [82-133] versus 69 [33-215], P < .001; 1.0 [0.3-2.9] versus 0.4 [0.01-1.6], P < .001, respectively). No significant differences were found in oxidized glutathione levels in women with preeclampsia (22 [5-49] versus 17 [2-60], P = .06) or free levels in preeclamptic women with HELLP syndrome (757 [624-993] versus 842 [539-1516], P = .09) as compared with normotensive pregnant women. The ratios of free to oxidized cysteinylglycine and glutathione were higher in women with HELLP syndrome than in those with preeclampsia (5.4 [3.3-12.7] versus 4.1 [2.3-11.6], P = .02, and 56 [28-124] versus 45 [16-166], P = .02, respectively).
Conclusion: Significantly lower ratios of free to oxidized cysteine, homocysteine, and cysteinylglycine in preeclampsia might indicate oxidative stress.
Obstetrics and Gynecology 01/2001; 97(2):272-276. · 4.73 Impact Factor
