Oxidative and carbonyl stress parameters and their informative value in women who used alcohol during the I trimester of pregnancy

BACKGROUND: Alcohol negatively affects the fetus, especially in the early stages of gestation. Ethanol promotes the formation of reactive species that are inactivated by the antioxidant defense system. Its important components are fat-soluble vitamins such as retinol and alpha-tocopherol. In this regard, the problem of optimizing the supply of these vitamins during pregnancy is extremely relevant. Both hypo- and hypervitaminosis can contribute to the development of pregnancy complications and the occurrence of fetal developmental abnormalities. AIM: The aim of this study was to assess retinol and alpha-tocopherol levels in the blood of women in the first trimester of pregnancy depending on the level of the alcohol consumption biomarker phosphatidylethanol. METHODS: This study included 167 women in the first trimester of pregnancy and 37 non-pregnant women of reproductive age. To identify the fact and amount of alcohol consumption, we performed a quantitative determination of phosphatidylethanol 16:0/18:1 in blood plasma using high-performance liquid chromatography-mass spectrometry. Depending on the phosphatidylethanol concentration, groups of women consuming different doses of alcohol were identified: Group 1 — phosphatidylethanol value ≤ 8 ng/ml (non-drinkers, n = 63); Group 2 — phosphatidylethanol value ranged from 8 to 45 ng/ml (drinkers of less than one dose, n = 68); Group 3 — phosphatidylethanol value 45 ng/ml (drinkers of more than one dose, n = 36). The levels of retinol and alpha-tocopherol were determined by the fluorimetric method. RESULTS: Both the alpha-tocopherol and retinol levels were higher in Groups 2 and 3 compared to the control values (p 0.05). When compared to the group of non-pregnant women, the alpha-tocopherol level was lower in the groups of non-drinking pregnant women (p 0.001) and those drinking less than one dose of alcohol (p = 0.012), with the retinol level being lower only in the group of non-drinking women (p 0.001). CONCLUSION: Even small doses of alcohol consumed by pregnant women affect the retinol and alpha-tocopherol levels, which can increase the risk of pregnancy complications and fetal abnormalities.

Background. Even small amounts of alcohol have an extremely negative effect on the fetus, especially in the early stages of gestation. It is known that ethanol promotes the formation of free radicals, but there is no data on the nature of the oxidative stress development in pregnant women depending on its blood level.The aim. To assess the level lipid peroxidation products and superoxide dismutase activity in the first trimester of pregnancy for women, who consumed alcoholic bevera ges, depending on the phosphatidylethanol (PEth) level in the blood.Materials and methods. The study included 165 women in the first trimester of pregnancy aged 18 to 40 years. To identify the fact and amount of alcohol consumption, the direct biomarker of alcohol 16:0/18:1PEth in blood plasma was performed using high-performance liquid chromatography with tandem mass spectrometry. Depending on the concentration of PEth, groups of women consuming different doses of alcohol were identified: group 1 – PEth concentration < 8 ng/ml (non-drinkers; n = 63); group 2 – PEth concentration from 8 to 45 ng/ml (drinkers of less than 1 dose; n = 66); group 3 – PEth concentration ≥ 45 ng/ml (drinkers of more than 1 dose; n = 36). The content of lipid peroxidation products and superoxide dismutase activity was determined by spectrophotometric methods.Results. It was found that lipid peroxidation intermediates level in the groups of women who consume alcohol, regardless of PEth 16:0/18:1 level in blood plasma, was significantly higher compared with the control (p < 0.05). The superoxide dismutase activity was higher in the group of pregnant women who consumed less than 1 dose of alcohol compared with the control (p < 0.05) and the group who consumed one or more doses of alcohol (p < 0.05).Conclusion. The obtained results indicate the activation of lipid peroxidation processes in the first trimester of pregnancy regardless of the dose of alcohol-containing products consumed.

Beyond other beneficial effects, a soy-rich diet has been shown to reduce the risk of cardiovascular diseases and diabetic complications. Reduction of oxidative and carbonyl stress has been proposed as the underlying mechanism, but the evidence for this is lacking. The aim of our study was to evaluate the effects of short-term increased soy intake on oxidative and carbonyl stress parameters in young volunteers. Young healthy probands (omnivores) of both genders (55 women, 33 men) were given soybeans (2 g/kg bodyweight daily) for one week. Markers of oxidative and carbonyl stress were measured in plasma at the beginning and at the end of one week soybean intake and after another week of a wash-out period. Total antioxidant capacity was increased by soybean intake in both genders. This led to decreased levels of advanced oxidation protein products in women, but not in men. On the contrary, in men, soybean intake increased lipoperoxidation. No effects on carbonyl stress markers (advanced glycation end products-specific fluorescence and fructosamine) were found. Soybean intake has gender-specific effects on oxidative stress in young healthy probands potentially due to divergent action and metabolism of phytoestrogens in men and women. Effects of soybean intake on carbonyl stress should be evaluated in longer studies.

Pregnant women are particularly susceptible to sleep-disordered breathing. Obstructive sleep apnea (OSA) in pregnancy is associated with poor pregnancy and fetal outcomes. Oxidative stress caused by intermittent hypoxemia and reoxygenation may impact pregnancy health. We hypothesize that pregnant women with OSA have a pronounced oxidative stress profile. A case-control study was performed to study oxidative stress markers in the serum of pregnant women with or without OSA. Patients with OSA were identified between 2003 and 2009. Contemporaneous controls were pregnant subjects without apnea, gasping, or snoring around the time of delivery. Serum markers of oxidative and carbonyl stress were measured by spectrophotometric/fluorometric methods. Multiple linear regression analysis was used with a model including age, body mass index at delivery, history of diabetes, and gestational age. Serum samples from 23 OSA cases and 41 controls were identified. Advanced oxidation protein products, a marker for oxidative stress, and advanced glycation end products (AGEs), a marker for carbonyl stress, were significantly lower in women with OSA than in controls (p value <0.0001). Total antioxidant capacity was higher in women with OSA in comparison to controls (p value <0.0001). The difference in AGEs remained significant even after adjusting for confounders. Contrary to our hypothesis, the results of this study suggest that pregnant women with OSA have higher antioxidant capacity and lower oxidative and carbonyl stress markers compared to controls, suggesting a possible protective effect of intermittent hypoxia. Whether OSA in pregnancy impacts oxidative stress differently than OSA in the general population remains to be confirmed.

The first trimester of pregnancy is characterized by continuous proliferation, invasion and differentiation of cytotrophoblasts. These processes are precisely controlled both, in space and time by molecules such as endothelin-1 (ET-1). ET-1 is expressed in human first trimester trophoblast and is known to stimulate cytotrophoblast proliferation through endothelin A and B receptor subtypes (ET(A) and ET(B)), and cytotrophoblast invasion through ET(B). However, temporal changes of the ET system during the first trimester of pregnancy have not been previously studied. This study tested the hypothesis that ET-1 release, ET(A) and ET(B) expression are increased towards the end of the first trimester of pregnancy (weeks 10-12 vs. weeks 6-9), resulting in increased cytotrophoblast proliferation and invasion. Tissue samples were obtained from 17 surgical pregnancy interruptions (week 6-9: n=9; week 10-12: n=8). After cytotrophoblast isolation, the invasive and proliferative phenotypes were immune-separated by an alpha(6)-integrin antibody. Both proliferative and invasive cytotrophoblasts were cultured separately on plastic or Matrigel for 24 h. ET-1 release into the culture medium of both cytotrophoblast subtypes was measured by radioimmunoassay. ET(A) and ET(B) mRNA expression was measured by RT-PCR, and the ET-1 effect on cytotrophoblast proliferation and invasion was determined using proliferation and invasion assays, respectively. ET-1 release increased from early to late first trimester of pregnancy in both proliferative (1.8-4.5 fold) and invasive cytotrophoblasts (9.3-28 fold), especially when cultured on Matrigel. This was paralleled by less ET(B) mRNA on invasive cytotrophoblasts independent of the time period in first trimester, whereas ET(A) expression was similar on proliferative an invasive cytotrophoblasts. Proliferation and invasion of cytotrophoblasts under control conditions decreased from early to late first trimester. ET-1 stimulated both processes at both periods with the most pronounced effect (7-fold) on invasion in late first trimester. The ET-1/ET-receptor system changes between weeks 6-9 and 10-12 in pregnancy. Our data suggest an autocrine and endocrine ET-1 effect, which is stronger in late than in early first trimester of pregnancy paralleled by different stimulatory effects on trophoblast invasion and proliferation. In general, this suggests time as an additional effector of the critical processes governing placental development in the first trimester of human pregnancy.

To provide some insight into the mechanism of cervical ripening, the expression of type I collagen was investigated in human uterine cervical tissues obtained from the first (n = 4) and third (n = 3) trimesters of normal pregnancy. Indirect immunofluorescent staining was performed for type I collagen, and Northern blot analysis was done to assess expression of mRNA for the alpha1(I) chain. Collagens were also extracted from the human cervical tissues in the first and third trimesters of pregnancy. Immunohistochemical analysis revealed loose distribution of type I collagen in the uterine cervix of the first trimester compared with the third trimester of pregnancy. The relative levels of various collagens were evaluated by SDS-PAGE. The ratios of the intensity of the band of alpha1(I) to that of total collagen alpha1 chain in cervical tissues of the third trimester were significantly lower than those in cervical tissues of the first trimester of pregnancy (P < 0.05). In contrast, the ratios of the intensity of the band of alpha1(III) to that of total collagen alpha1 chain in cervical tissues of the third trimester were significantly higher than those in cervical tissues of the first trimester of pregnancy (P < 0.05). Northern blot analysis revealed that the cervical expression of mRNA for the alpha1(I) chain was significantly reduced in the third trimester compared with the first trimester of pregnancy (P < 0.01). These results suggest that type I collagen might play an important role in the maintenance of pregnancy and that decreased expression of this collagen could be associated with the process of uterine cervical ripening.

Background: The aim of the study was to assess the contribution of carbonyl and oxidative stresses to the development of amyloidosis in patients suffering from chronic rheumatic diseases, and the potential influence of renal function to their concentrations was considered. Methods: We investigated 17 patients with chronic rheumatological diseases and histologically proven diagnosis of AA amyloidosis (group AA-RA), 26 patients suffering from rheumatoid arthritis without any signs of AA amyloidosis (group nonAA-RA) and 20 healthy volunteers (Co). In all patients, advanced glycation end products (AGEs), advanced oxidation protein products (AOPP), pregnancy-associated plasma protein A (PAPP-A) and other selected proinflammatory markers were measured. Results: An increase in serum levels of AOPP and AGEs was found in the AA-RA group in comparison with nonAA-RA patients and also with Co (p < 0.001 for all comparisons). AGEs positively correlated with serum creatinine (r = 0.67, p = 0.004) and negatively with glomerular filtration rate (r = –0.54, p = 0.027). We did not find a correlation between AOPP and any other assessed parameters including proteins and renal parameters. PAPP-A levels were not significantly increased in any group of patients (AA-RA, nonAA-RA) in comparison with Co. Conclusions: Increased plasma levels of AGEs and AOPP in the group of patients with AA-RA may have been partly explained by the diminished renal clearance. However, the increase in AOPP levels was higher than what is expected in this degree of renal failure (glomerular filtration rate in the AA-RA group corresponding to chronic kidney disease stage III).

Principal component analysis of some oxidative stress parameters and their relationships in hemodialytic and transplanted patients

157-LB: Scanning Frequency and Glucose Variability in the First Trimester of T1DM Pregnancies Predict Time Spent in Very Low Glucose Range in the Last One—Analysis of Intermittently Scanned Continuous Glucose Monitoring

Pregnancy-induced hypertension diseases are classified as gestational hypertension, preeclampsia, or eclampsia. The mechanisms of their development and prediction are still to be discovered. Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is an angiogenic factor secreted by the placenta during the first trimester of human pregnancy that was shown to control trophoblast invasion, to be upregulated by hypoxia, and to be abnormally elevated in pathological pregnancies complicated with preeclampsia and intrauterine growth restriction. These findings suggested that sustaining EG-VEGF levels beyond the first trimester of pregnancy may contribute to pregnancy-induced hypertension. To test this hypothesis, osmotic minipumps delivering EG-VEGF were implanted subcutaneously into gravid OF1 (Oncins France 1) mice on day 11.5 post coitus, which is equivalent to the end of the first trimester of human pregnancy. Mice were euthanized at 15.5 and 18.5 days post coitus to assess (1) litter size, placental, and fetal weights; (2) placental histology and function; (3) maternal blood pressure; (4) renal histology and function; and (5) circulating soluble fms-like tyrosine kinase 1 and soluble endoglin. Increased EG-VEGF levels caused significant defects in placental organization and function. Both increased hypoxia and decreased trophoblast invasion were observed. Treated mice had elevated circulating soluble fms-like tyrosine kinase 1 and soluble endoglin and developed gestational hypertension with dysregulated maternal kidney function. EG-VEGF effect on the kidney function was secondary to its effects on the placenta as similarly treated male mice had normal kidney functions. Altogether, these data provide a strong evidence to confirm that sustained EG-VEGF beyond the first trimester of pregnancy contributes to the development of pregnancy-induced hypertension.

Oxidative stress impairs endothelial function and may play an important role in the pathogenesis of acute cardiovascular diseases. Advanced oxidation protein products (AOPP) were proposed as one of the possible markers of oxidative injury, which originates under oxidative and carbonyl stress and increase global inflammatory activity. The present study was undertaken to compare AOPP concentrations in a control group of healthy individuals without ICHS (I), patients with stable angina pectoris (II), patients with acute coronary syndrome over 48 hours without ST elevations (III), and patients with ST elevation myocardial infarction (IV). Coronaronary angiography, risk factors and anamnestic data were analyzed. We examined 73 probands with signs of myocardial ischemia, mean age of 61.5 years (64% males) subjected to coronarography and 21 healthy individuals. No significant difference was found between venous blood and coronary samples, or between infarction and non-infarction arteries in the group IV. AOPP concentrations in healthy individuals in the group I (82.9 +/- 29.3 mmol/l) did not differ significantly from patients in group II (89.6 +/- 26.7 mmol/l) and group III (112.3 +/- 54.6 mmol/l). A significant difference in AOPP values was found between the groups I and IV, and between the groups II and IV (82.9 +/- 29.3 mmol/l vs. 125.8 +/- 101 mmol/l, p = 0.02, and 89.6 +/- 26.7 mmol/l vs. 125.8 +/- 101 mmol/l, p = 0.02). No correlations were found between AOPP and body mass index (BMI), nicotinism, left ventricular ejection fraction, parameters of glucose and lipid metabolism. ROC analysis revealed that AOPP concentrations of 89 mmol/l had 64% sensitivity and 71% specificity for revealing an acute coronary syndrome (AUC 0.65, 95% CI 0.55-0.80). AOPP are significantly increased in patients with acute coronary syndromes with ST segment elevation, but also tend to increase in patients with non-ST elevation myocardial infarction. Our observations suggest that AOPP may be used as a marker of oxidative stress and as a prognostic factor for severe forms of cardiovascular disease. A cut-off value of 89 mmol/l can be used with 64% sensitivity and 71% specificity for revealing acute coronary syndrome.

Background: Residual renal function (RRF) affects the survival rate and the development of cardiovascular disease in peritoneal dialysis (PD) patients. We evaluated the impact of RRF on oxidative and carbonyl stress in PD patients. Methods: Plasma advanced oxidation protein products (AOPP) and pentosidine were measured in PD patients with a urine volume of ≥300 ml/day (group A, n = 17) and <300 ml/day (group B, n = 14). AOPP and pentosidine were reevaluated after 12 months of follow-up in group A. Results: Plasma levels of AOPP and pentosidine in group A were significantly lower than those in group B. Renal creatinine clearance was inversely correlated with AOPP (p < 0.05) and pentosidine (p < 0.01). After 12 months of follow-up, no significant change was observed in AOPP and pentosidine in groups who maintained a urine volume of ≥300 ml/day, but significantly increased in groups whose urine volume decreased to less than 300 ml/day. There were significant inverse relationships between the changes in renal creatinine clearance and AOPP (p < 0.01) and pentosidine (p < 0.05). Conclusion: Loss of RRF is associated with increased plasma AOPP and pentosidine, indicating that preservation of RRF has a beneficial effect in reducing the oxidative and carbonyl stress in PD patients.

Increased oxidative stress is a hallmark of end-stage renal disease (ESRD). Glutathione S-transferases (GST) are involved in the detoxification of xenobiotics and protection of oxidative damage. We hypothesized that genetic polymorphism in antioxidant enzymes GSTA1, GSTM1, GSTP1 and GSTT1 is more frequent in ESRD and modulates the degree of oxidative stress in these patients. GSTA1, GSTM1, GSTP1 and GSTT1 genotypes were determined in 199 ESRD patients and 199 age- and gender-matched controls. Markers of protein and lipid oxidative damage [thiol groups, carbonyl groups, advanced oxidative protein products, nitrotyrosine, malondialdehyde (MDA) and MDA adducts], together with total oxidant status and pro-oxidant-antioxidant balance were determined. Individual GST polymorphisms influence vulnerability to both protein and lipid oxidation, with GSTM1-null gene variant having the most pronounced effect. Furthermore, a strong combined effect of null/low-activity GSTM1, GSTT1, GSTA1 and GSTP1 genotypes in terms of susceptibility towards oxidative and carbonyl stress was found in ESRD patients. When patients were stratified according to GSTM1 and GSTT1, the highest oxidant damage was noted in those with the GSTM1-null/GSTT1-null genotype. The observed effect was even stronger in patients with the third low-activity GSTP1 or GSTA1 genotype. Finally, the level of oxidative and carbonyl stress was most pronounced in the subgroup of patients with all four null or low-activity GSTM1, GSTT1, GSTP1 and GSTA1 genotypes. According to the GST genotype, ESRD patients may be stratified in terms of the level of oxidative and carbonyl stress that might influence cardiovascular prognosis, but could also improve efforts towards individualization of antioxidant treatment.

Oxidative stress appears to be involved in the pathogenesis of osteoporosis-a serious complication of anorexia nervosa (AN). We evaluated the oxidative status in adolescent girls with AN and its potential relationship with bone mineral density (BMD). Girls with AN (n = 43) and age-matched healthy controls (n = 20) underwent anthropometric and BMD examination. Markers of bone turnover, oxidative stress, and antioxidant status were measured. Participants with AN and controls did not differ in BMD at the lumbar spine (p = 0.17) and total body less head BMD (p = 0.08). BMD at the total hip was lower (p < 0.001) in the AN group compared with the controls. Levels of antioxidant status markers-ferric reduction antioxidant power, total antioxidant capacity, and reduced and oxidized glutathione ratio (all p < 0.001)-were significantly lower, whereas those of advanced oxidation protein products (AOPP), fructosamines, and advanced glycation end products (AGEs) (all p < 0.001) were higher in AN patients than in healthy controls. BMD and bone turnover markers were positively correlated with antioxidant status markers, while they were negatively correlated with AOPP, fructosamines, and AGEs levels. Conclusion: This is the first study to assess a potential association between oxidative status and BMD in adolescents with AN. We demonstrated that in young girls, the imbalance of oxidative status and reduced BMD are concurrently manifested at the time of the diagnosis of AN. Disturbance of oxidative status could play a pathogenetic role in AN-associated decreased BMD. What is Known: • Osteoporosis is a serious complication of AN, and in affected adolescents may result in a permanent deficit in bone mass. • Oxidative and carbonyl stress may be involved in the development of bone loss. What is New: • Adolescents girls with AN have impaired antioxidant defense and increased oxidative damage to biomolecules. • Disturbance of oxidative status could affect bone loss and could contribute to decreased BMD in adolescent females with AN.

Salivary markers of oxidative stress in patients with oral premalignant lesions