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This review addresses the general hypothesis that the pathogenesis of preeclampsia is related to an imbalance of increased oxidative stress and lipid peroxidation coupled to a deficiency of antioxidant protection. Evidence will be presented that this imbalance is present in both the maternal compartment and the placental compartment and that interactions between these two compartments result in the clinical manifestations of this disorder. We suggest the following as a scenario for the development of preeclampsia: Oxidative stress in the maternal compartment affects the placenta in such a way as to bring about a decrease in placental antioxidant enzyme protection. The oxidative stress in the maternal compartment may be preexisting (e.g., obesity, diabetes, hyperlipidemia) or may be caused by placental secretion of lipid peroxides. Decreased placental antioxidant enzyme protection leads to a cascade of events in the placenta of uncontrolled lipid peroxidation with increased thromboxane production and increased tumor necrosis factor (TNF-alpha) production. Increased placental secretion of lipid peroxides and/or TNF-alpha results in activation of leukocytes as they circulate through the intervillous space. The activated leukocytes serve as circulating mediators that link the increased oxidative stress of the placenta with a widespread increase in oxidative stress and endothelial dysfunction in the mother. In the third trimester, when the placenta is growing rapidly, the mother's antioxidant capacity is no longer able to compensate, and the clinical symptoms of preeclampsia appear.
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PMID:Maternal-placental interactions of oxidative stress and antioxidants in preeclampsia. 965 11

The antioxidants and lipid peroxidation products are being extensively studied because of their potential importance and pathogenetic role in several non-communicable diseases like cardiovascular diseases and cancer, but the data on hypertension is scanty. Therefore, the present study aimed to assess the levels of lipid peroxidation and antioxidants besides dislipidemia changes among 32 newly diagnosed male hypertensives by comparing them with an equal sample of normotensives. Significant increase in serum lipid peroxide levels and decrease in antioxidant enzyme superoxide dismutase and vitamins E and A were observed among hypertensives than the controls. Hypertensives had higher total cholesterol, low-density lipoprotein cholesterol, triglycerides, body mass index and low high-density lipoprotein cholesterol levels than normotensives. The percentage prevalence of hypercholesterolemia, hypertriglyceridemia, low high-density lipoprotein cholesterol and obesity was higher in study subjects. Obese hypertensives had significantly higher levels of lipid peroxides and lipids with no change in antioxidant status than normal-weight hypertensives. Our results suggest that hypertensive patients may have elevated lipid peroxidation, lipids and reduced protection from antioxidants, which may contribute to the propensity in such patients to develop cardiovascular diseases, and to correct this, antioxidant supplementation besides weight reduction may be helpful to reduce the severity of burden.
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PMID:Antioxidants, lipid peroxidation and lipoproteins in primary hypertension. 1097 48

Chronic renal failure often induces left ventricular hypertrophy. We assessed whether the heart is affected in the Zucker obese rat, a model of chronic renal failure associated with obesity, glucose intolerance, and insulin resistance without hypertension or hyperglycemia. After systemic blood pressure measurement, the heart, the aorta, and the kidneys were removed from anesthetized 9- and 13-mo-old Zucker obese and lean control male rats (n = 33, n = 24, n = 25, and n = 21, respectively). Determination of left ventricular geometry, quantification of myocardium collagen density, and measurement of heart antioxidant enzyme activity were made, as well as aorta and kidney parameters. Mean blood pressure remained at a normal range whatever the age and group considered. Whereas kidney structure and function were severely impaired, no sign of myocardial infarction or inflammatory process was noticed. A moderate left ventricular hypertrophy was observed in 13-mo-old obese rats. While heart malondialdehyde was stable with age and among groups, antioxidant enzyme activity was higher in obese rats. In conclusion, in the absence of hypertensive or hyperglycemic disorders, the heat seems to display a sufficient line of defense against oxidative stress during the development of cardiac hypertrophy.
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PMID:High levels of myocardial antioxidant defense in aging nondiabetic normotensive Zucker obese rats. 1467 Aug 9

We have evaluated the possible association of polycystic ovary syndrome (PCOS) with 15 genomic variants previously described to influence insulin resistance, obesity, and/or type 2 diabetes mellitus. Seventy-two PCOS patients and 42 healthy controls were genotyped for 15 variants in the genes encoding for paraoxonase (three variants), plasma cell differentiation antigen glycoprotein, human sorbin and SH3 domain containing 1, plasminogen activator inhibitor-1, peroxisome proliferator-activated receptor-gamma2, protein tyrosine phosphatase 1B (two variants), adiponectin (two variants), IGF1, IGF2, IGF1 receptor, and IGF2 receptor. Compared with controls, PCOS patients were more frequently homozygous for the -108T variant in paraoxonase (36.6% vs. 9.5%; P = 0.002) and homozygous for G alleles of the ApaI variant in IGF2 (62.9% vs. 38.1%; P = 0.018). Paraoxonase is a serum antioxidant enzyme and, because -108T alleles result in decreased paraoxonase expression, this increase in oxidative stress might result in insulin resistance. G alleles of the ApaI variant in IGF2 may increase IGF2 expression, and IGF2 stimulates adrenal and ovarian androgen secretion. In conclusion, the paraoxonase -108 C-->T variant and the ApaI polymorphism in the IGF2 gene are associated with PCOS and might contribute to increased oxidative stress, insulin resistance, and hyperandrogenism in this prevalent disorder.
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PMID:Association of the polycystic ovary syndrome with genomic variants related to insulin resistance, type 2 diabetes mellitus, and obesity. 1518 Oct 35

Cellular glutathione peroxidase-1 (GPX1) is the first identified and the most abundant selenoprotein in mammals. Although GPX1 has been widely considered to be a major antioxidant enzyme, there has been no direct evidence for such role in vivo until GPX1 transgenic and null mice became available 10 y ago. Using these new models, we demonstrated that GPX1 protects against oxidative stress mediated by reactive oxygen species (ROS), and the physiologic importance of this protection varies with insult level and body Se status. Full expression of GPX1 is needed, and overexpression of GPX1 is beneficial for Se-adequate mice to defend against severe oxidative stress. This function of GPX1 is associated with attenuating the prooxidant-induced oxidation of NADPH, NADH, lipid, and protein in various tissues. In Se-deficient mice, a minute amount of GPX1 activity (4% of adequate levels) protects against hepatic aponecrosis induced by mild oxidative stress. In contrast, knockout of GPX1 renders mice and their hepatocytes resistant to oxidative stress related to reactive nitrogen species (RNS). More intriguingly, mice overexpressing GPX1 develop insulin resistance and obesity, accompanied by a downregulation of insulin-mediated phosphorylations of insulin receptor and Akt protein. In conclusion, GPX1 seems to play contrasting roles in coping with ROS vs. RNS, and its metabolic functions extend beyond redox regulation.
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PMID:New roles for an old selenoenzyme: evidence from glutathione peroxidase-1 null and overexpressing mice. 1617 85

TNF-alpha is a key molecule in obesity-related metabolic disturbances. This study was designed to determine whether N-acetylcysteine (NAC), an antioxidant, prevents the activation of nuclear factor-kappaB (NF-kappaB) by exogenously administered TNF-alpha in adipocytes, and whether such change affects the production of adipocytokines. The treatment of well-differentiated 3T3-L1 cells with 20 mM of NAC significantly increased the reduced glutathione concentration up to 150% of control. The treatment with 10 ng/ml of TNF-alpha decreased antioxidant enzyme levels such as CuZn-superoxide dismutase (SOD), MnSOD and catalase, and activated NF-kappaB in 3T3-L1 adipocytes. The activation of NF-kappaB was significantly prevented by the pretreatment with 20 mM of NAC. TNF-alpha (1-10 ng/ml) dose-dependently increased interleukin (IL)-6 and plasminogen activator inhibitor-1 (PAI-1) secretion from 3T3-L1 adipocytes, while decreased adiponectin secretion. NAC (5-20 mM) attenuated the TNF-alpha-induced changes in these adipocytokine secretions in a dose-dependent manner. The effect of TNF-alpha and NAC on the adipocytokine productions was exerted at the m-RNA level, judging from results of the real time RT-PCR analysis. The present study revealed that NAC inhibited the TNF-alpha-mediated activation of NF-kappaB and improved the adverse changes in the levels of IL-6, PAI-1 and adiponectin in 3T3-L1 adipocytes. NAC may have the potential to improve the obesity-related abnormal adipocytokine metabolism by attenuating the TNF-alpha-induced oxidant-antioxidant imbalance in adipocytes.
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PMID:N-acetylcysteine attenuates TNF-alpha induced changes in secretion of interleukin-6, plasminogen activator inhibitor-1 and adiponectin from 3T3-L1 adipocytes. 1695 78

Obesity is well known to be a contributory risk factor for several disease states, including diabetes mellitus. Further, obese women are more prone to have babies born with congenital abnormalities. Paucity of data on maternal-fetal disposition of essential trace elements in obese pregnancies prompted us to undertake this study. Maternal venous and umbilical arterial and venous samples were collected from obese patients (body mass index >30) and control pregnant women (body mass index <25) at time of spontaneous delivery or cesarean sections and concentrations of essential trace elements such as Cu, Fe, Mo, Se, and Zn determined in various samples by atomic absorption spectrophotometry. Activities of antioxidant enzymes, superoxide dismutase, glutathione peroxidase, and total antioxidant activity in maternal and umbilical blood were assessed using appropriate reagent kits. Maternal-fetal disposition and exchange parameters of elements studied were assessed using established criteria. Concentrations of Cu, Fe, Mo, Se, and Zn in the serum of control pregnant women at time of delivery averaged 2232.6, 2398.1, 10.9, 108.9, and 661.9 microg/L respectively, whereas in the obese group, the values of the above elements averaged 2150.3, 2446.8, 12.6, 96.8, and 838.9 microg/L respectively. Umbilical vein/maternal vein ratios of Cu, Fe, Mo, Se, and Zn in the control group averaged 0.29, 1.93, 1.06, 0.76, and 1.12, respectively, whereas in the obese group, their fetal-maternal ratios averaged 0.32, 2.23, 1.06, 0.78, and 1.53, respectively. The Cu : Zn ratio in the maternal vein of the obese group (3.60 +/- 0.20) was significantly lower (Student's t-test; p < 0.05) than that of the controls (2.50 +/- 0.19); however, Cu : Fe ratio (1.04 +/- 0.08 vs 1.02 +/- 0.09) was not significantly different (Student's t-test; p > 0.05) in the two groups. Varying differences were noted in the case of antioxidant enzyme activities between the control and study groups. We conclude that obesity is associated with alterations in maternal-fetal disposition of some essential trace elements and antioxidant enzyme status and that these alterations could pose a potential health risk for the mother as well as the fetus.
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PMID:Maternal-fetal status of copper, iron, molybdenum, selenium, and zinc in obese pregnant women in late gestation. 1719 14

Obesity and its associated metabolic pathologies are the most common and detrimental diseases, affecting over 50% of the adult population. Our knowledge about the protective effects of melatonin against high-fat diet (HFD)-induced obesity is still marginal. In this investigation, we hypothesized that melatonin can minimize the metabolic pathologies and morphological changes associated with obesity in animals receiving an HFD. To examine these effects, and to test our hypothesis, an animal model formed of male Boscat white rabbits was established. The animals were divided into three groups: (i) a control group fed regular diet; (ii) an obesity group fed an HFD for 12 weeks; and (iii) a treated group fed HFD for 12 weeks and then treated with melatonin for 4 weeks. The animals were killed and their serum and tissues were evaluated for: (i) lipid profile (cholesterol, triglycerides and low-density lipoprotein) and glucose; (ii) antioxidant enzyme (serum glutathione peroxidase, GSH-PX); and (iii) fatty changes (liver, kidney and blood vessels). Compared with the control group, intake of HFD (obesity group) was associated with: (i) a statistically significant increase in blood pressure, heart rate, sympathetic nerve activity, body weight, food consumption, serum lipids, blood glucose levels and atherogenic index; (ii) decreased level of GSH-PX and high-density lipoprotein (HDL); and (iii) fatty changes in the liver and kidney as well as atheromatous changes in the blood vessels. Compared with the obesity group, intake of melatonin (treated group) was associated with: (i) a statistically significant decrease in blood pressure, heart rate, sympathetic nerve activity, body weight, food consumption, serum lipids, blood glucose levels and atherogenic index; (ii) increased level of GSH-PX and HDL; and (iii) disappearance of fatty changes in the liver and kidney as well as atheromatous changes in the blood vessels. The administration of melatonin reduced the metabolic pathologies associated with the intake of HFD, suggesting a protective role. Although the underlying mechanisms are unclear, they may include its antioxidant and receptor-mediated effects. The clinical ramifications of these effects await further investigations.
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PMID:Intake of melatonin is associated with amelioration of physiological changes, both metabolic and morphological pathologies associated with obesity: an animal model. 1724 35

Obesity is well known to be a contributory risk factor for several disease states, including diabetes mellitus. Paucity of data on maternal-foetal status of essential trace elements in obese diabetic pregnancies prompted us to undertake this study. Maternal venous and umbilical arterial and venous blood samples were collected from obese gestational diabetic patients (Body Mass Index (BMI) >30) and control obese pregnant women (BMI>30) at time of spontaneous delivery or caesarean sections and concentrations of essential trace elements such as Cu, Fe, Mo, Se and Zn were determined in various samples by atomic absorption spectrophotometry. Activities of antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPX) and total antioxidant (TAO) in maternal and umbilical blood were assessed using appropriate reagent kits. Maternal-foetal disposition and exchange parameters of elements studied were assessed using established criteria. Concentrations of Cu, Fe, Mo, Se and Zn in serum of control obese pregnant women (n=10) averaged 2404, 2663, 11.0, 89.0 and 666 microg/l respectively, while in the obese diabetic group (n=11), the corresponding values averaged 2441, 2580, 13.3, 85.1 and 610 microg/l respectively. Activities of antioxidant enzymes such as SOD, GPX and TAO were not significantly different in maternal veins of control and diabetic groups. Varying differences were noted in the case of antioxidant enzyme activities in umbilical blood samples of control and study groups. We conclude that obesity is not associated with significant alterations in antioxidant enzyme status in gestational diabetes and only with relatively minor alterations in status of some essential trace elements.
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PMID:Maternal-foetal status of copper, iron, molybdenum, selenium and zinc in obese gestational diabetic pregnancies. 1772 48

Hypothyroidism enhances the progression of atherogenesis. Furthermore, dyslipidemia, hypertension, and obesity are known risk factors for atherosclerosis. Oxidative stress is implicated in the pathogenesis of cardiovascular diseases. However, there are contradicting reports on the existence of oxidative stress in hypothyroidism. Thus, the aim of the study is to evaluate the presence of oxidative stress in hypothyroidism and, if so, its possible association with various coronary lipid risk factors. The present study was carried out in a group of 27 freshly diagnosed normotensive primary hypothyroid female patients in comparison with healthy subjects. Their body mass index (BMI), serum thyroid profile, lipid profile, glucose, protein carbonylation, thiobarbituric acid reactive substances (TBARS), and blood antioxidant enzyme levels were estimated. The TBARS and protein carbonylation were significantly higher in cases compared with those in controls. Reduced glutathione was lower and glutathione peroxidase was higher in the test group compared with those in controls. Various lipid risk factors for coronary artery disease were significantly higher among the hypothyroid women in comparison with those in controls. The level of TBARS correlated significantly with various lipid risk factors among the hypothyroid women even after correcting the effect of BMI. However, no significant associations were observed between BMI and these risk factors when the effect of TBARS was nullified. In hypothyroidism, the coronary lipid risk factors seem to be more associated with lipid peroxidation than BMI. In conclusion, the present study indicates the presence of oxidative stress in hypothyroid patients and its association with atherogenic dyslipidemia, which is independent of BMI.
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PMID:Association between oxidative stress and coronary lipid risk factors in hypothyroid women is independent of body mass index. 1788 44


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