Lipid peroxidation affects red blood cells membrane properties in patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune, chronic inflammatory, non-organ specific disease with an important morbimortality affecting several organs and systems. Oxidative stress is a well documented mechanism of red blood cells (RBC) mechanical impairment. Free radicals could produced, through lipid peroxidation, physical and chemical alterations in the cellular membrane properties modifying its composition, packing and lipid distribution on the membrane erythrocyte. The aim of the present work is to study the lipid peroxidation in the RBC membrane in SLE patients (n = 42) affecting so far the lipid membrane fluidity and erythrocyte deformability in comparison with healthy controls (n = 52). Malonildialdehyde (MDA) is a subrogate assessing lipidic peroxidation, rigidity index estimating erythrocyte deformability and the anisotropy coefficient estimating lipid membrane fluidity were used. Our results show that MDA values are increased, while erythrocyte deformability and membrane fluidity are significantly decreased in erythrocyte membrane from SLE patients in comparison with normal controls. The association of thiobarbituric acid reactive substances (TBARS) with membrane lipid fluidity and erythrocyte deformability confirms that the damage of membrane properties is produced by lipid peroxidation.

Erythrocyte aggregation in patients with systemic lupus erythematosus.

Systemic Lupus Erythematosus (SLE) is an autoimmune, chronic inflammatory, non-organ specific disease. SLE patients present a high prevalence of thrombotic and arteriosclerotic disease. The aim of the present work was to study the erythrocyte aggregation kinetics, and the effect of plasma factors, namely, immunoglobulin and fibrinogen concentration, as well as cell factors such as deformability and erythrocyte membrane lipid fluidity on the erythrocyte aggregation, in SLE patients and healthy controls. The results show that SLE patients red blood cells aggregate at higher rate and the aggregates size are also greater than controls due to an increase of immunoglobulin and plasma fibrinogen. The negative correlation between aggregation parameters and rigidity index could point out that the altered deformability diminishes the erythrocyte aggregation. Correlation between rigidity index and anisotropy suggests that the decrease of membrane lipid fluidity might be a cause of deformability decrease. The erythrocyte aggregation increase in these patients could induce a decreased flow that might contribute to the thromboembolic process present in SLE patients.

Effects of ascorbate fatty ester derivatives on erythrocyte membrane lipoperoxidation.

6-O-alkyl ascorbic acid esters (ASC(n)) are amphiphilic molecules that behave as surfactants in aqueous solution. ASC(n) have shown some physical and rheological properties that suggest a potential utility as drug carriers. The present paper aims to evaluate the effect of ASC(n) on erythrocyte properties in order to get information regarding the relationship between osmotic fragility, erythrocyte deformability and membrane lipoperoxidation process. The assays were performed at the following concentrations: the critical micelar concentration (CMC), producing 10% hemolysis (CH(10)) and producing 50% hemolysis (CH(50)). We observed that ASC(n) (ASC(8), ASC(10) and ASC(12)), at concentration nearby CMC, neither affected cell deformability nor produced lipoperoxidation. Nevertheless, at higher concentrations (CH(10) and CH(50)), the RBCs incubated with ASC(n) were affected by a significant and progressive loss of deformability, simultaneously with an increase of osmotic fragility and membrane lipoperoxidation.

Study on membrane fluidity and erythrocyte aggregation in equine, bovine and human species.

The aim of the present paper is to analyze whether membrane fluidity can be predicted from its lipid composition and to assay the possible relationship between such variable and the aggregating properties of erythrocytes from equine, bovine and human species due to the widely acknowledged differences in their tendency to form aggregates. The main difference between phospholipids from plasma membrane in these species lies in the concentration levels of sphyngomyelin (SM) and phosphatidilcoline (PC); more precisely, in the external hemilayer of the lipid bilayer. Membrane fluidity was estimated by the fluorescence polarization method, while erythrocyte aggregation was assessed by an optical method. According to our results, bovine erythrocytes containing high SM and low PC levels, presented the highest anisotropy value as well as an imperceptible aggregation value. Equine erythrocytes, which contain a considerable PC percentage and scarce SM levels, showed the lowest anisotropy value and the highest values of the aggregation parameters. Human erythrocytes presented intermediate values for both properties. Our hypothesis claims that the phospholipid composition would constitute one of the factors determining erythrocyte membrane fluidity and also taking part in the different aggregation tendency shown by equine, bovine and human species.

Nifedipine effect on red cell rheological properties in patients with systemic scleroderma.

Systemic scleroderma is an autoimmune disease, due to a connective tissue alteration characterized by extracellular matrix increase in the skin and internal organs. It is already known that the Raynaud's phenomenon and the microcapillary obliteration lead to ischemia and peripheral tissue injury. The ischemia-reperfusion phenomenon releases free radicals, that react with red blood cells (RBCs) membrane components originating lipid peroxidation and impairment of the ATP-Ca(++) pump, two possible mechanisms responsible of disease pathogenesis. Nifedipine is a Ca(++)-channel antagonist that has been used for a long time in Raynaud's phenomenon treatment. In the present study we were able to demonstrate that erythrocyte deformability and two other related variables such as membrane fluidity and osmotic fragility improve significantly with nifedipine therapy. It is likely that nifedipine inhibiting cytoplasmic calcium accumulation could restore some red blood cell membrane properties.

Effect of ascorbic acid based amphiphiles on human erythrocytes membrane.

6-O-alkyl ascorbic acid esters (ASCn) are amphiphilic molecules that behave as surfactants in aqueous solution. These compounds show physico-chemical and aggregation properties that depend on the alkyl chain length, pH and temperature. It must consider that ASCn have shown some physical and rheological properties that suggest a potential utility as drug carriers. The present paper aims to evaluate the effects of these surfactants on human erythrocyte membranes. The membrane properties studied were: osmotic resistance in hypotonic media, shape transformation, and vesicle release at lytic concentration. According to our results, all properties depended on the length of the hydrophobic chain and they did not evolve monotonically. Finally, the study of ASCn interaction with erythrocyte membrane allowed us to postulate the crucial influence that the molecular structure exerts upon the manner in which amphiphiles interact with biological membranes and the effects involved in them.

Association between capillaroscopy, haemorheological variables and plasma proteins in patients bearing Raynaud's phenomenon.

Raynaud's phenomenon is a paroxysmal and reversible vasospasm affecting generally the acral circulatory regions. The relevance of the haemorheological alterations in these patients, as a source of ischemic events has been neglected. The objective of the present work was to evaluate and correlate the rheological blood properties, some biochemical parameters, e.g., plasma fibrinogen and immunoglobulin levels, and periungual capillaroscopy. The explicative variables considered were: blood viscosity, plasma viscosity, erythrocyte rigidity index, plasma fibrinogen, erythrocyte sedimentation rate, erythrocyte aggregate size, erythrocyte aggregation rate and serum immunoglobulin (IgG and IgM). The response variable was the nailfold capillary pattern categorised as either normal or pathological. Fibrinogen, erythrocyte aggregation rate and IgM are significantly higher in patients with a pathological pattern in comparison with patients bearing a normal one. The statistical analysis enabled us the modelling of the pathological pattern occurrence probability in function of plasma fibrinogen. Consequently, 100 mg/dl plasma fibrinogen increase, increases twice the probability of presenting a pathological pattern. Therefore, we can conclude that high levels of fibrinogen in Raynaud's phenomenon patients are associated with impaired skin microcirculation assessed by periungual capillaroscopy.

Effect of hormone replacement therapy upon haemorheological variables.

It is already admitted that hormone replacement therapy (HRT) decreases the risk of developing cardiovascular disease, although its mechanism is not clear yet. In the present work, the effect of the HRT upon cellular and plasmatic haemorheological factors determining blood flow properties: blood viscosity, plasma viscosity, plasma fibrinogen, rigidity erythrocyte index and erythrocyte aggregation rate was studied. Menopausal women were followed through a whole year of HTR. Results demonstrate that after six months of treatment there is a diminution in relative blood viscosity and erythrocyte rigidity, with constant values along the second semester. Erythrocyte aggregation, plasmatic and blood viscosity diminution observed during the treatment can be explained by the simultaneous plasma fibrinogen decrease. Modified cellular and plasmatic rheology could produce beneficial effects on blood flow, particularly in microcirculation, presenting a possible mechanism by which HTR decreases the risk of cardiovascular disease development during menopause.

Influence of plasma proteins on erythrocyte aggregation in three mammalian species.

The aggregation capacity of human erythrocytes lies between that of the non-aggregating bovine erythrocytes and the remarkably aggregating equine ones. As the ability to aggregate is attributed to cell factors and the composition of the plasma proteins, the role that plasma proteins play in the aggregation process in these three species was studied. Washed erythrocytes were suspended in phosphate-buffered saline (PBS; pH 7.4, 300 mOsm/L) plus polyvinylpyrrolidone (PVP) in a suitable concentration to obtain an average intensity of aggregation (control media). The superimposed effect of replacing 80% of the medium by either autologous plasma, serum or albumin solution was studied. The plasma proteins appeared to enhance aggregation by human and equine erythrocytes, but impaired this process in bovine erythrocytes. Some evidence was obtained supporting the existence of serum factors capable of reducing aggregation of erythrocytes in cattle and it was concluded that the non-aggregating behaviour of bovine erythrocytes may be due to the cells interacting particularly with the macromolecules in the serum.