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Osmotic lysis curves of intact red blood cells from normotensive and preeclamptic pregnant women. OS 50 is defined as the osmolar concentration that produces 50% hemolysis of the added red blood cells. The lyses were performed as indicated in the Materials and Methods section. Values are means ± S.E. of 6 experiments with different preparations.
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To evaluate the osmotic fragility and level of lipid peroxidation of red blood cells from pregnant women with severe preeclampsia, treated or not with MgSO(4).
Osmotic fragility and lipid peroxidation of red blood cells was evaluated in 11 normotensive pregnant women and eleven pregnant women with severe preeclampsia.
MgSO(4) therapy, either in viv...
Contexts in source publication
Context 1
... in membrane fluidity is considered one of the most important factors for the determination of osmotic fragility of red blood cell (33). We assayed the red blood cells from both normotensive and preeclamptic pregnant women for osmotic fragility, and the results are shown in Figure 1. The red blood cells of the preeclamptic women are more sensitive to the osmotic shock than those from the normotensive women, as shown by the significantly higher OS 50 . ...
Context 2
... can be seen that just 4 min of treatment of the intact red blood cells from normotensive pregnant women with the Fenton reaction are enough to increase the OS 50 to values similar to those seen for intact red blood cells from preeclamptic pregnant women (Figure 1). Then, we assayed the OS 50 and the level of lipid peroxidation (as TBARS) from intact red blood cells from normotensive pregnant women treated for 4 min with the Fenton reaction, in the presence and absence of 4 mM MgSO 4 . ...
Context 3
... can also cause increased osmotic fragility, by altering the membrane protein composition and structure, due to the proteolytic action of bacterial toxins on the membrane (36). The increased membrane lysis in response to a hypoosmotic shock, observed for red blood cells from preeclamptic women, as compared to control pregnant women (Figure 1), is in agreement with previous findings (34). These results are consistent with the increased level of lipid peroxidation found for the red cell membranes of the preeclamptic women, as peroxidation of polyunsaturated fatty acid chains can disrupt the membrane and reduce its fluidity. ...
Citations
... Fortunately, Mg 2+ replenishment in inflammatory pathologies associated with Mg 2+ deficiency through supplementation is favorable. Clinic and pre-clinic studies showed decreased inflammatory biomarkers and disease improvement (Table 4) [8,170,171,[204][205][206][207][208][209][210][211]. These optimistic and encouraging results suggest using Mg 2+ as an immunomodulatory agent, a regulator of inflammation and associated conditions, thus preventing the development of severe or chronic inflammation [3,163,205]. ...
Magnesium (Mg2+) is an essential mineral nutrient, necessary for many biochemical reactions in the human body, including energy metabolism, protein and DNA synthesis, maintenance of the electrical potential of nervous and cardiac tissues, control of blood glucose, and regulation of blood pressure. However, currently, the world population suffers from a severe problem because the consumption of Mg2+ in the diet is deficient and generalized in the populations. Mg2+ deficiency causes oxidative stress (OS) due to the increase in reactive oxygen species (ROS) that originate from mitochondrial dysfunction, activation of the renin-angiotensin-aldosterone system (RAAS), and abnormal regulation of calcium homeostasis. In addition, Mg2+ deficiency also causes inflammation by increasing the production of proinflammatory molecules such as interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha (TNF-α), which in turn can exacerbate the production of ROS. The combination of inflammation and OS induced by Mg2+ deficiency increases the risk of developing chronic diseases. This review describes Mg2+ deficiency, its complications, and its relationship with OS and chronic inflammatory diseases. In addition, the importance of increasing the intake of Mg2+ throughout the world is highlighted.
... In addition, increased membrane lysis has been demonstrated in response to the hypoosmotic shock, to which red blood cells from pregnant women with preeclampsia were subjected, compared with gestational controls. This has been correlated with lipid peroxidation of this membrane caused by the elevated oxidative stress in in vivo and in vitro assays [253][254][255][256][257]. Therefore, the assay of osmotic fragility of red blood cells could be an easy and affordable assay to evaluate oxidative stress in vivo. ...
... Since intravenous therapy with magnesium sulfate (MgSO 4 ) is the treatment of choice to stabilize the preeclamptic pregnant woman to avoid eclampsia, our group evaluated the effect of treatment with this salt on the levels of lipid peroxidation and PMCA activity in red blood cells. It was found that treatment with MgSO 4 protects and prevents oxidative damage of the plasma membrane, not only in vivo but also in vitro [181,253,409,410]. To try to explain these findings, we performed computational simulations and modeling, using quantum chemistry and molecular dynamic calculations for a model lipid bilayer and hydrated ion pairs of MgSO 4 and found that this salt adsorbs on the membrane surface near the phosphate groups. ...
Oxidative stress is the result of an imbalance between the formation of reactive oxygen species (ROS) and the levels of enzymatic and non-enzymatic antioxidants. The assessment of biological redox status is performed by the use of oxidative stress biomarkers. An oxidative stress biomarker is defined as any physical structure or process or chemical compound that can be assessed in a living being (in vivo) or in solid or fluid parts thereof (in vitro), the determination of which is a reproducible and reliable indicator of oxidative stress. The use of oxidative stress biomarkers allows early identification of the risk of developing diseases associated with this process and also opens up possibilities for new treatments. At the end of the last century, interest in oxidative stress biomarkers began to grow, due to evidence of the association between the generation of free radicals and various pathologies. Up to now, a significant number of studies have been carried out to identify and apply different oxidative stress biomarkers in clinical practice. Among the most important oxidative stress biomarkers, it can be mentioned the products of oxidative modifications of lipids, proteins, nucleic acids, and uric acid as well as the measurement of the total antioxidant capacity of fluids in the human body. In this review, we aim to present recent advances and current knowledge on the main biomarkers of oxidative stress, including the discovery of new biomarkers, with emphasis on the various reproductive complications associated with variations in oxidative stress levels.
... Additionally, red blood cells from experimental rats displayed higher osmotic fragility compare to control rats. Interestingly, similar results have been described in preeclamptic women (Abad et al., 2005(Abad et al., , 2010(Abad et al., , 2015b. ...
... The osmotic fragility of red blood cells was determined according to a method described elsewhere (Abad et al., 2010). The osmotic fragility curves were fitted with the Boltzmann equation for sigmoidal fitting, using the software Origin ® (OriginLab Corporation, United States). ...
Preeclampsia (PE) is a pregnancy-specific syndrome with multisystem involvement which leads to fetal, neonatal, and maternal morbidity and mortality. A model of salt-loaded pregnant rats has been previously studied, sharing several pathological characteristics of preeclamptic women. In this study, it was compared the effects of the treatment with an oral magnesium salt, magnesium gluconate (Mg-gluconate), on the osmotic fragility of red blood cells, lipid peroxidation, and PMCA activity of placental homogenates and red blood cell ghosts in salt-loaded pregnant rats. Mg-gluconate has a higher antioxidant capacity than MgSO 4 due to the presence of several hydroxyl groups in the two anions of this salt. Salt-loaded pregnant rats received 1.8% NaCl solution ad libitum as a beverage during the last week of pregnancy. On day 22nd of pregnancy, the rats were euthanized and red blood cells and placenta were obtained. Salt-loaded pregnant rats showed an increased level of lipid peroxidation and a lowered PMCA activity in placental and red blood cell ghosts, as well as an increased osmotic fragility of their red blood cells. The treatment of the salt-loaded pregnant rats with Mg-gluconate avoids the rise in the level of lipid peroxidation and the concomitant lowering of the PMCA activity of their red blood cell membranes, reaching values similar to those from control pregnant rats. Also, this treatment prevents the increase of the osmotic fragility of their red blood cells, keeping values similar to those from control pregnant rats. Mg-gluconate seems to be an important candidate for the replacement of the MgSO 4 treatment of preeclamptic women.
... The injury caused to cell membranes by oxidative stress has been associated with several diseases and inflammatory responses in humans and animals [5], such as Parkinson's [6,7], Alzheimer's [7][8][9], hypoxia/reoxygenation [10][11][12][13][14][15], preeclampsia [16][17][18][19][20][21][22][23][24], hypertension [19,25], renal failure [25,26], pulmonary illness [27], cancer [28,29], and other pathological processes [30]. ...
... The injury caused to cell membranes by oxidative stress has been associated with several diseases and inflammatory responses in humans and animals [5], such as Parkinson's [6,7], Alzheimer's [7][8][9], hypoxia/reoxygenation [10][11][12][13][14][15], preeclampsia [16][17][18][19][20][21][22][23][24], hypertension [19,25], renal failure [25,26], pulmonary illness [27], cancer [28,29], and other pathological processes [30]. ...
... In the literature, magnesium salts have been experimentally reported to decrease the LP effects, e.g. in preeclampsia [16][17][18][19][20][21][22][23][24]. Thus, Chiarello et al. [20] concluded that the treatment of MgSO 4 in women with preeclampsia has been beneficial in the restoring of endothelial functions, inactivating brain N-methyl-D-aspartate (NMDA) receptors, reducing the inflammatory response, and the oxidative stress; being not only beneficial to the mother but also the neonate. ...
Magnesium sulfate (MgSO4) has been used as a protector agent for many diseases related to oxidative stress. The effect of MgSO4 on the oxidized lipid bilayer has not yet been studied using molecular dynamics calculations. In this work, the effects of oxidation were evaluated by using a POPC membrane model at different concentrations of its aldehyde (-CHO) and hydroperoxide (-OOH) derivatives with and without MgSO4. Several quantitative and qualitative properties were evaluated, such as membrane thickness, area per lipid, area compressibility modulus, snapshots after simulation finish, density distributions, time evolutions of oxidized group positions, and radial distributions of oxidized group concerning Mg. Results indicate that in the absence of MgSO4 the mobility of oxidized groups, particularly –CHO, toward the surface interface is high. At a low oxidation level of the bilayer there is an increase in the compressibility modulus as compared to the unoxidized bilayer. MgSO4, at a low oxidation level, tends to lessen the oxidation effects by lowering the dispersion in the distribution of oxidized species toward the membrane surface and the water region. However, MgSO4 does not change the trends of decreasing membrane thickness and area compressibility modulus and increasing area per lipid upon oxidation. In this regard, MgSO4 diminishes the electrostatic long-distance attractive interactions between the oxidized groups and the charged headgroups of the interface, owing to the Mg⁺² and SO4⁻² screening effects and an electrostatic stabilization of the headgroups, preventing the pore formation, which is well-known to occur in oxidized membranes.
... Although the evaluation of osmotic stability of the erythrocyte membrane is well established in the literature [23,24], the number of studies on osmotic stability of erythrocyte membrane in preeclampsia is still quite small [11,21,25]. ...
... In this study, the hematologic involvement of the disease was associated with greater osmotic stability of erythrocyte membrane. This has already been demonstrated in other stud- ies [11,18,25,42]. But this study is the first to demonstrate the occurrence of increased erythro- cyte membrane stability under conditions of osmolarity that are equivalent to those existing in vivo. ...
The objective of this study was to analyze the relationships of osmotic and mechanical stability of erythrocytes with anthropometric, biochemical, hematologic and hemodynamic variables in pregnant women with preeclampsia (PE). The studied population consisted of 20 normotensive patients and 16 patients with PE. Patients with PE presented worse gestational outcome, greater hematologic impairment, erythrocytes osmotically more stable in vitro, but in conditions of isotonicity with the in vivo medium, in addition to hyperflow in orbital territory, when compared to normotensive patients. The correlation analysis between anthropometric, hematologic and hemodynamic variables in patients with PE indicated that erythrocytes with lower volumes and lower levels of hemoglobin favor the occurrence of a better gestational outcome, because they are more stable and because they are associated with a decrease in the hemodynamic changes present in the disease. This should mean that the tendency to microcytosis, probably due to a mechanism of compensatory mechanical selection, is a desirable characteristic in the disease.
... There have been many reports that resistance to osmotic pressure in RBCs is a useful indicator for evaluating the strength of the cell membrane. Osmotic fragility (OF) in RBCs is a valuable for expressing the robustness of membrane against osmotic pressure and is generally used for evaluating the interaction of various chemicals and the cell membrane in vitro, including general [1,2] and local anesthetics [3,4], some kinds of drugs [5,6] and toxins [7,8], inorganic [9,10] and organic compounds [11,12], as well as substances isolated from plants [13,14], and crude plant extracts [15,16]. Although the RBCs of various mammalian species were used in those experiments, it has not been considered if the differences in OF response are based on inter-species differences in RBC membrane characteristics. ...
... Endothelial dysfunction is the common pathway to all forms of presentation of the disease [5]. In PE, there is an imbalance between pro-and antioxidant factors, which characterizes the state of oxidative stress and can be proven by the elevation of biomarkers of lipid peroxidation in relation to normotensive pregnant women [26,43]. ...
... Previous studies indicate that both gestation and PE are associated with changes in blood rheological behavior [46][47][48][49][50][51]. Although PE was previously associated with increased osmotic fragility of erythrocytes [43], in this study the EOPE group showed a signi cant increase in membrane osmotic stability in relation to the C group and a borderline increase in relation to the LOPE group. ese results suggest that EOPE and LOPE actually have di erent etiologies. ...
Preeclampsia (PE) is classified as early-onset PE (EOPE) and late-onset PE (LOPE) when present before or after 34 weeks of gestation, respectively. This transversal study aimed to investigate the differences and possible associations existing in the anthropometric, hemodynamic, hematologic, and biochemical profiles of late- and early-onset preeclampsia. The study included 65 volunteers admitted to a tertiary hospital in Brazil: 29 normotensive and 36 with preeclampsia (13 with EOPE and 23 with LOPE). Pregnant women with LOPE presented greater weight gain and borderline increase in body mass index at the end of gestation in relation to the other groups, which is compatible with the metabolic origin, associated with obesity, attributed to this form of the disease. Pregnant women with EOPE presented a borderline reduction in the number of erythrocytes and a significant decrease in the number of platelets, in addition to a significant increase in reticulocytes, serum iron, and ferritin when compared to normotensive pregnant women and pregnant women with LOPE. A significant increase in osmotic stability of erythrocytes was observed in the EOPE group in relation to other groups. Hemodynamic analysis by Doppler ultrasonography of the ophthalmic artery showed that both groups of pregnant women with PE presented alterations compatible with the occurrence of hyperflow in the orbital territory. These hemodynamic changes were associated with changes in hematimetric indices.
... There have been many reports that osmotic fragility (OF) in RBCs is a valuable tool for assessing the actions of various chemicals on the cell membrane in vitro. General [1] and local anesthetics [2], certain kinds of drugs [3] and toxins [4], inorganic [5] and organic compounds [6], as well as substances isolated from plants [7], and crude plant extracts [8], all induce changes in OF in the RBCs of various mammalian species. ...
In sheep red blood cells (RBCs), considering osmotic fragility (OF) as an indicator, the reaction of monocarboxylic and dicarboxylic acids on membrane resistance to osmotic pressure were evaluated. Sheep RBCs were exposed to carboxylic acids at 0-100 mM in a buffer solution for 1 h and the 50% hemolysis was then determined by soaking in 0.1-0.8% NaCl solution. Although formic acid declined and n-caprylic acid increased OF, most of the monocarboxylic acids with straight hydrocarbon chains did not change OF in sheep RBCs. Whereas, all the tested dicarboxylic acids with straight hydrocarbon chains decreased OF with the degree of the decrease in OF dependent on the compound. Some monocarboxylic acids with branched or cyclic (including a benzene ring) hydrocarbon chains decreased OF with the degree of the decrease dependent on the number of carbons and form of branching in the hydrocarbon chain. Dicarboxylic acids with a cyclohexane ring or benzene ring decreased or tended to decrease OF with the degree of the decrease dependent on the position of the two carboxylic groups. There is no clear correlation between the effect of monocarboxylic or dicarboxylic acids on OF, and their partition coefficients. Thus the partition coefficient is not a suitable parameter for explaining the effect of both groups of carboxylic acid on the cell membrane as evaluated by the change in OF in sheep RBCs. It is speculated that the space composed of the acyl-chains of the phospholipids, into which hydrophobic hydrocarbons can enter to form a more rigid structure through their subsequent interaction, is an important factor related to the OF-decreasing effect of carboxylic acids.
... Cell fragility is strongly dependent on its intrinsic membrane properties and it is increased by reduction of the membrane fluidity [12], as it has been shown for red blood cells of preeclamptic women with increased levels of lipid peroxidation [24]. In this particular, we found an increased osmotic fragility of red blood cells of pregnant women with IUGR (Figure 2), a condition that can be explained considering a lowered capacity of deformability of their cell membranes, induced by the structural changes and their consequent reduced fluidity derived from their increased level of lipid peroxidation. ...
... This is largely due to the lack of understanding of molecular kinetic mechanisms of MgSO 4 action. In particular, the role of the influence of magnesium on erythrocytes in blood is known (Abad et al., 2005(Abad et al., , 2010Ariza et al., 2005;Gulczynska et al., 2006), but far from completely understood. In some cases, the anti-hypoxic mechanism of the protection through the activation of erythrocytes physiological properties by magnesium is supposed (Szemraj et al., 2005), but not explained quantitatively. ...
