RESUMEN
This work presents a semi-quantitative spectroscopic approach, including FTIR-ATR and Raman spectroscopies, for the biochemical analysis of red blood cells (RBCs) supported by the biochemical, morphological and rheological reference techniques. This multi-modal approach provided the description of the RBC alterations at the molecular level in a model of accelerated aging induced by administration of D-galactose (D-gal), in comparison to natural aging. Such an approach allowed to conclude that most age-related biochemical RBC membrane changes (a decrease in lipid unsaturation and the level of phospholipids, or an increase in acyl chain shortening) as well as alterations in the morphological parameters and RBC deformability are well reflected in the D-gal model of accelerated aging. Similarly, as in natural aging, a decrease in LDL level in blood plasma and no changes in the fraction of glucose, creatinine, total cholesterol, HDL, iron, or triglycerides were observed during the course of accelerated aging. Contrary to natural aging, the D-gal model led to an increase in cholesterol esters and the fraction of total esterified lipids in RBC membranes, and evoked significant changes in the secondary structure of the membrane proteins. Moreover, a significant decrease in the phosphorous level of blood plasma was specific for the D-gal model. On the other hand, natural aging induced stronger changes in the secondary structures of the proteins of the RBCs' interior. This work proves that research on the aging mechanism, especially in circulation-related diseases, should employ the D-gal model with caution. Nonetheless, the D-gal model enables to imitate age-related rheological alterations in RBCs, although they are partially derived from different changes observed in the RBC membrane at the molecular level.
Asunto(s)
Envejecimiento Prematuro/inducido químicamente , Envejecimiento/sangre , Modelos Animales de Enfermedad , Membrana Eritrocítica/química , Galactosa/toxicidad , Espectroscopía Infrarroja por Transformada de Fourier , Espectrometría Raman , Envejecimiento Prematuro/sangre , Animales , Citosol/química , Envejecimiento Eritrocítico/efectos de los fármacos , Deformación Eritrocítica/efectos de los fármacos , Índices de Eritrocitos/efectos de los fármacos , Membrana Eritrocítica/efectos de los fármacos , Radicales Libres/toxicidad , Galactosa/farmacología , Hemorreología/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Fósforo/sangre , Proyectos de InvestigaciónRESUMEN
BACKGROUND: An adequate erythrocyte function is vital for tissue oxygenation and wound healing. The erythrocyte membrane phospholipid composition plays an important role in erythrocyte function and administration of omega-3 fatty acids may provide a means to improve it. OBJECTIVE: To investigate peri-operative erythrocyte function and effects of oral omega-3 fatty acids in morbidly obese women undergoing gastric bypass surgeryMETHODS:Fifty-six morbidly obese women undergoing laparoscopic Roux-en-Y gastric bypass (LRYGB) surgery were randomized between a low calorie diet (LCD) during 2 weeks or oral omega-3 poly-unsaturated fatty acids (n-3 PUFAs) and a normal diet during 4 weeks. Peri-operative blood samples were analyzed with the Lorrca MaxSIS Ektacytometer for erythrocyte deformability and aggregability. RESULTS: There were no significant differences in erythrocyte function between the groups at any time point. Only erythrocyte aggregability parameters were affected by surgery. At six month follow-up, aggregation index (AI) and cholesterol, glucose and insulin were significantly improved. CONCLUSIONS: In this study, oral Omega-3 supplementation did not affect erythrocyte function compared to a LCD. Six months after surgery a significant improvement in AI and metabolic parameters was observed in both groups, contributing to a reduction in the risk at thromboembolic and cardiovascular complications.
Asunto(s)
Suplementos Dietéticos/análisis , Agregación Eritrocitaria/efectos de los fármacos , Deformación Eritrocítica/efectos de los fármacos , Membrana Eritrocítica/efectos de los fármacos , Ácidos Grasos Omega-3/uso terapéutico , Derivación Gástrica/métodos , Laparoscopía/métodos , Obesidad Mórbida/cirugía , Adolescente , Adulto , Anciano , Ácidos Grasos Omega-3/farmacología , Femenino , Humanos , Intestinos/efectos de los fármacos , Persona de Mediana Edad , Resultado del Tratamiento , Adulto JovenRESUMEN
Many hypotheses have been proposed to explain how a glutamate to valine substitution in sickle haemoglobin (HbS) can cause sickle cell disease (SCD). We propose and document a new mechanism in which elevated tyrosine phosphorylation of Band 3 initiates sequelae that cause vaso-occlusion and the symptoms of SCD. In this mechanism, denaturation of HbS and release of heme generate intracellular oxidants which cause inhibition of erythrocyte tyrosine phosphatases, thus permitting constitutive tyrosine phosphorylation of Band 3. This phosphorylation in turn induces dissociation of the spectrin-actin cytoskeleton from the membrane, leading to membrane weakening, discharge of membrane-derived microparticles (which initiate the coagulation cascade) and release of cell-free HbS (which consumes nitric oxide) and activates the endothelium to express adhesion receptors). These processes promote vaso-occlusive events which cause SCD. We further show that inhibitors of Syk tyrosine kinase block Band 3 tyrosine phosphorylation, prevent release of cell-free Hb, inhibit discharge of membrane-derived microparticles, increase sickle cell deformability, reduce sickle cell adhesion to human endothelial cells, and enhance sickle cell flow through microcapillaries. In view of reports that imatinib (a Syk inhibitor) successfully treats symptoms of sickle cell disease, we suggest that Syk tyrosine kinase inhibitors warrant repurposing as potential treatments for SCD.
Asunto(s)
Anemia de Células Falciformes/tratamiento farmacológico , Proteína 1 de Intercambio de Anión de Eritrocito/metabolismo , Procesamiento Proteico-Postraduccional/efectos de los fármacos , Anemia de Células Falciformes/sangre , Adhesión Celular/efectos de los fármacos , Micropartículas Derivadas de Células/química , Evaluación Preclínica de Medicamentos , Endotelio Vascular/metabolismo , Deformación Eritrocítica/efectos de los fármacos , Membrana Eritrocítica/efectos de los fármacos , Eritrocitos Anormales/efectos de los fármacos , Eritrocitos Anormales/metabolismo , Hemoglobina Falciforme/análisis , Humanos , Mesilato de Imatinib/farmacología , Mesilato de Imatinib/uso terapéutico , Estrés Oxidativo , Oxígeno/sangre , Fosforilación/efectos de los fármacos , Fosfotirosina/metabolismo , Plasma , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Rasgo Drepanocítico/sangre , Talasemia beta/sangreRESUMEN
BACKGROUND: An adequate erythrocyte function is vital for tissue oxygenation and wound healing. The erythrocyte membrane phospholipid composition plays an important role in erythrocyte function and administration of omega-3 fatty acids may provide a means to improve it. OBJECTIVE: To investigate peri-operative erythrocyte function and effects of omega-3 fatty acidsMETHODS:Forty-four patients undergoing elective laparoscopic colon resection for non-metastasized cancer were randomized between intravenous omega-3 poly-unsaturated fatty acids (n-3 PUFAs) or placebo (saline). Peri-operative blood samples were analyzed with a Lorrca MaxSIS Ektacytometer and erythrocyte membrane phospholipids were determined with gas chromatography. RESULTS: Patient and operation characteristics were equal between groups. There was a significant increase in erythrocyte membrane eicosapentaenoic acid (EPA) but not docosahexaenoic acid (DHA) in the n-PUFA group. There were no significant differences in erythrocyte deformability but the aggregation index (AI) was significantly lower and the aggregation half time (T½) was significantly higher in the n-3 PUFA group. CONCLUSION: This study confirms rapid changes in erythrocyte membrane phospholipid composition after administration of intravenous n-3 PUFAs. Erythrocyte deformability parameters were not affected but erythrocyte aggregability was decreased in the n-3 PUFA group. Further investigation is necessary to gain more insights in the effects of n-3 PUFA and the postoperative inflammatory response on erythrocyte function.
Asunto(s)
Neoplasias del Colon/complicaciones , Agregación Eritrocitaria/efectos de los fármacos , Deformación Eritrocítica/efectos de los fármacos , Membrana Eritrocítica/efectos de los fármacos , Ácidos Grasos Omega-3/uso terapéutico , Anciano , Anciano de 80 o más Años , Neoplasias del Colon/patología , Método Doble Ciego , Ácidos Grasos Omega-3/farmacología , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: RRx-001 is an anti-cancer immunotherapeutic that increases the sensitivity of drug resistant tumors via multiple mechanisms which involve binding to hemoglobin and enhancing nitrite reductase activity of deoxyhemoglobin. OBJECTIVE: In the present study, the effect of clinically used doses of RRx-001 on erythrocyte deformability was examined. METHODS: A dose dependent effect of RRx-001 (1-1000 micro molar) on erythrocyte deformability was measured by ektacytometer under hypoxia (n = 8). Low dose RRx-001 (20 micro molar) in the presence of ODQ (1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one), L-NAME (L-NG-Nitroarginine methyl ester) or nitrite were examined both in normoxia and hypoxia. Intracellular nitric oxide (NO) levels were measured fluorometrically with DAF-FM-DA. RESULTS: Higher doses of RRx-001 (100, 1000 micro molar) significantly decreased erythrocyte deformability under hypoxia (p < 0.01; p < 0.05, respectively). RRx-001 (20 micro molar), alone or in combination with ODQ or L-NAME, did not change deformability. However, RRx-001 and nitrite caused an increase in deformability (p < 0.01) under hypoxia. RRx-001 induced NO production was more pronounced in the presence of nitrite (p < 0.05). CONCLUSIONS: Co-administration of RRx-001 and nitrite under hypoxic conditions results in a significant increase in erythrocyte deformability that is related to increased NO production. We suggest that measurement of serum nitrite level in RRx-001 treated cancer patients should be routinely undertaken and supplemented if levels are low for maximal activity.
Asunto(s)
Antineoplásicos/farmacología , Azetidinas/farmacología , Neoplasias/sangre , Óxido Nítrico/sangre , Nitritos/farmacología , Nitrocompuestos/farmacología , Biomarcadores/sangre , Deformación Eritrocítica/efectos de los fármacos , Eritrocitos/citología , Eritrocitos/efectos de los fármacos , Humanos , NG-Nitroarginina Metil Éster/farmacología , Neoplasias/tratamiento farmacológicoRESUMEN
Hemorheological properties represent significant contributors in the pathogenesis of cardiovascular diseases. As plasma vitamin C is inversely associated with blood viscosity in humans, we aimed to characterize the effect of vitamin C supplementation on hemorheology with an emphasis on erythrocyte functions. Twenty young healthy volunteers were asked to take vitamin C (1000 mg per day) for 3 weeks. We observed beneficial effect of intervention on multiple hemorheological parameters: whole blood viscosity in the range of medium to high shear rates, Casson yield stress, complex viscosity, and storage and loss moduli. As erythrocyte properties play a significant role in hemorheology, we characterized their deformability, nitric oxide production, and sodium pump activity in erythrocyte membranes. We can conclude that observed promotion in whole blood rheology may be consequence of improved erythrocyte functionality as concerns their ability to pass through narrow capillaries of the microcirculation, nitric oxide production, and sodium pump activity. Parameters reflecting oxidative stress and antioxidant status in plasma were not affected by our intervention. As improvement in hemorheology may play an important role in cardioprotection, it would be challenging to investigate the vitamin C supplementation to patients suffering from microcirculatory disturbances and worsened organ perfusion in the case of cardiovascular diseases.
Asunto(s)
Ácido Ascórbico/farmacología , Suplementos Dietéticos , Deformación Eritrocítica/efectos de los fármacos , Eritrocitos/citología , Eritrocitos/efectos de los fármacos , Hemorreología/efectos de los fármacos , Adulto , Membrana Eritrocítica/efectos de los fármacos , Membrana Eritrocítica/metabolismo , Eritrocitos/metabolismo , Femenino , Humanos , Masculino , Óxido Nítrico/biosíntesis , Oxidación-Reducción/efectos de los fármacos , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Adulto JovenRESUMEN
BACKGROUND: Ozone is used intensively worldwide in treatment and research of various pathologies due to its healing effects. OBJECTIVE: The aim of this study is to investigate the effect of major ozone autohemotherapy on erythrocyte deformability and aggregation. METHODS: 10 and 50µg/ml doses of ozone was applied for 20 minute to venous blood samples obtained from 10 healthy male volunteers. Erythrocyte aggregation, deformability were measured by an ektacytometer. Total oxidant status, total antioxidant status were measured via a commercial kit. The oxidative stress index was calculated. RESULTS: Ozone at 10 and 50µg/ml doses did not alter erythrocyte aggregation. 50µg/ml ozone increased red blood cell (RBC) deformability measured at 0.53 Pa. Compared with the Control value, there was a significant increase in TOS, TAS for the doses of 10 and 50µg/ml. The increase in TAS was found to be more significant at 10µg/ml dose. The most obvious increase in OSI value was observed at 50µg/ml. CONCLUSION: Our results demonstrate that although 10µg/ml ozone has no effect on hemorheology, 50µg/ml ozone concentration has positive effects on RBC deformability, thus circulation at 0.53 Pa corresponding to the shear stress encountered during venous circulation.
Asunto(s)
Agregación Eritrocitaria/efectos de los fármacos , Deformación Eritrocítica/efectos de los fármacos , Hemorreología , Ozono/química , Adulto , Voluntarios Sanos , Humanos , Masculino , Estrés Oxidativo , Estrés MecánicoRESUMEN
BACKGROUND: L-Arginine, the precursor of NO might be involved in improving the cardiovascular disorders via regulation of functional properties of erythrocytes. OBJECTIVE: This study investigated the effects of L-Arginine supplementation on responses of red blood cell (RBC) properties to high intensity interval exercise (HIIE). METHODS: Ten overweight healthy men participated voluntarily in the study and performed two HIIE trials with and without L-Arginine in two separate weeks. The HIIE protocol included 12 intervals of 3-min encompassed 1-min running at 100% of vVO2max and 2-min active recovery at 40% of vVO2max. Three blood samples were taken before and after supplementation, and immediately after exercise; and were used to measure red blood cell properties. RESULTS: The HIIE protocol increased hematocrit, hemoglobin and lactate significantly (Pâ<â0.05), but had no significant effect on RBC aggregation, RBC deformability, and fibrinogen concentration. When data were compared for two trials no significant differences between the responses of RBC properties to two HIIE protocols were detected (Pâ>â0.05), whereas the increases in lactate concentration following HIIE was significantly lower in L-Arginine than placebo trial (Pâ<â0.05). CONCLUSIONS: It is concluded that L-Arginine consumption prior to HIIE does not lead to any improvement in RBC properties during HIIE in overweight healthy men.
Asunto(s)
Arginina/uso terapéutico , Agregación Eritrocitaria/efectos de los fármacos , Deformación Eritrocítica/efectos de los fármacos , Ejercicio Físico/fisiología , Hemorreología/efectos de los fármacos , Adulto , Arginina/farmacología , Humanos , Masculino , Adulto JovenRESUMEN
Bedaquiline (BDQ) is a new drug from the family of diarylquinolines, which has a potent bactericidal activity against Mycobacterium tuberculosis. This paper has examined the interaction of BDQ with model membranes (liposomes and BLM) and rat erythrocytes. It was shown that BDQ (1-10â¯mol%) changed the thermotropic phase behavior of DMPC liposomes, leading to the lateral phase separation in the lipid bilayer and the formation of membrane microdomains. BDQ (10-50⯵M) was also demonstrated to cause permeabilization of lecithin liposomes loaded with the fluorescent dye sulforhodamine B. At the same time, it did not alter the ionic conductivity of BLM. A dynamic light scattering study showed that BDQ led to the emergence of two populations of light-scattering particles in the suspension of lecithin liposomes, suggesting that an aggregation of the vesicles took place. In rat erythrocytes, BDQ was found to induce changes in their size and shape, as well as aggregation and lysis of the cells.
Asunto(s)
Antituberculosos/farmacología , Diarilquinolinas/farmacología , Deformación Eritrocítica/efectos de los fármacos , Liposomas/metabolismo , Animales , Células Cultivadas , Dispersión Dinámica de Luz , Eritrocitos/citología , Eritrocitos/efectos de los fármacos , Eritrocitos/metabolismo , Colorantes Fluorescentes/química , Colorantes Fluorescentes/metabolismo , Lecitinas/química , Liposomas/química , Masculino , Ratas , Ratas Wistar , Rodaminas/química , Rodaminas/metabolismo , Espectrometría de FluorescenciaRESUMEN
AIM: We aimed to study the effects of thymoquinone on erythrocyte deformability in an experimental model of sepsis given before or after the initiation of the sepsis model. METHOD: The animals were grouped as (n = 6) control, nigella sativa, sepsis, sepsis group with administration of nigella sativa before sepsis development and sepsis group with nigella sativa administration after sepsis development. Cecal ligation and puncture model (CLP) was used to induce sepsis in the animals. The thymoquinone was given 1 hour before or after the CLP in the study groups with a dose of 500 mg·kg(-1). Erythrocyte deformability and relative resistance was calculated. RESULT: Relative resistance was increased in the sepsis groups when compared to the control group (p < 0.0001). Deformability index was increased in the sepsis group when compared to the other groups (p < 0.0001 in all groups). Sepsis group with after nigella sativa groups deformability index was significantly different from the deformability index in control group (p = 0.002). The use of nigella sativa before the initiation of sepsis corrected the deformability index significantly and the results were comparable to the control group (p = 0.078). CONCLUSION: Thymoquinone administration before induction of CLP was observed to have protective effects on these alterations in CLP sepsis (Tab. 1, Fig. 1, Ref. 26).
Asunto(s)
Benzoquinonas/farmacología , Deformación Eritrocítica/efectos de los fármacos , Perforación Intestinal/sangre , Sepsis/sangre , Animales , Ciego , Modelos Animales de Enfermedad , Ligadura , Masculino , Nigella sativa , RatasRESUMEN
OBJECTIVE: To show whether Danggui Sini plus Wuzhuyu Shengjiang Tang (DSWST) has any transient effect on erythrocyte deformability in normal subjects. METHODS: A total of 25 subjects [mean age (27.8 ¡À 1.8) years] was enrolled in this study. The study was designed as a cross-over trial in which the subjects took part for 2 d. On the first day, blood samples were collected at baseline and 1-2 h after administration of water, whereas, on the second day, instead of water, the subjects were administered DSWST after the baseline blood sampling. The blood samples collected at baseline and after the administration water or DSWST, were examined for erythrocyte deformability. RESULTS: The elongation index increased significantly after 2 h (P = 0.009) compared to the baseline after DSWST intake. However, after water intake, there was no significant difference observed. When comparing the percent change of erythrocyte deformability between DSWST and water, we found that after 2 h of administration, DSWST improved erythrocyte deformability significantly compared to water (P < 0.001). CONCLUSION: DSWST has a transient effect on erythrocyte deformability in normal subjects.
Asunto(s)
Medicamentos Herbarios Chinos/administración & dosificación , Deformación Eritrocítica/efectos de los fármacos , Adulto , Estudios Cruzados , Femenino , Humanos , MasculinoRESUMEN
Type II diabetes (T2D) is a pandemic characterized by pathological circulating inflammatory markers, high-glucose levels and oxidative stress. The hematological system is especially vulnerable to these aberrant circulating molecules, and erythrocytes (RBCs) show aberrant rheology properties, owing to the direct contact with these molecules. Pathological levels of circulating inflammatory markers in T2D therefore have a direct effect on the molecular and cellular structure of RBCs. Previous research has suggested that antioxidants may reduce oxidative stress that results from the pathological inflammatory markers. Particularly, polyphenol antioxidants like oligomeric proanthocyanidins (OPCs) may act as a hydroxyl mopping agent, and may have a positive effect on the deformability and membrane protein structure of RBCs from T2D. In this paper, we look at the effect of one such agent, Pinus massoniana bark extract (standardized to 95% oligomeric proanthicyanidins), on the RBC membrane structures and RBC shape changes of T2D, after laboratory exposure at physiological levels. Our methods of choice were atomic force microscopy and scanning electron microscopy to study RBC elasticity and ultrastructure. Results showed that in our hands, this OPC could change both the eryptotic nature of the RBCs, as viewed with scanning electron microscopy, as well as the elasticity. We found a significant difference in variation between the elasticity measurement values between the RBCs before and after OPC exposure (P-value <0.0001). In conclusion, the data from both these techniques therefore suggest that OPC usage might contribute to the improvement of RBC functioning.
Asunto(s)
Diabetes Mellitus Tipo 2/sangre , Membrana Eritrocítica/efectos de los fármacos , Eritrocitos/efectos de los fármacos , Pinus , Extractos Vegetales/farmacología , Proantocianidinas/farmacología , Anciano , Elasticidad , Deformación Eritrocítica/efectos de los fármacos , Membrana Eritrocítica/ultraestructura , Eritrocitos/ultraestructura , Femenino , Humanos , Masculino , Microscopía de Fuerza Atómica , Microscopía Electrónica de Rastreo , Persona de Mediana EdadRESUMEN
The system L neutral amino acid transporter (LAT; LAT1, LAT2, LAT3, or LAT4) has multiple functions in human biology, including the cellular import of S-nitrosothiols (SNOs), biologically active derivatives of nitric oxide (NO). SNO formation by haemoglobin within red blood cells (RBC) has been studied, but the conduit whereby a SNO leaves the RBC remains unidentified. Here we hypothesised that SNO export by RBCs may also depend on LAT activity, and investigated the role of RBC LAT in modulating SNO-sensitive RBC-endothelial cell (EC) adhesion. We used multiple pharmacologic inhibitors of LAT in vitro and in vivo to test the role of LAT in SNO export from RBCs and in thereby modulating RBC-EC adhesion. Inhibition of human RBC LAT by type-1-specific or nonspecific LAT antagonists increased RBC-endothelial adhesivity in vitro, and LAT inhibitors tended to increase post-transfusion RBC sequestration in the lung and decreased oxygenation in vivo. A LAT1-specific inhibitor attenuated SNO export from RBCs, and we demonstrated LAT1 in RBC membranes and LAT1 mRNA in reticulocytes. The proadhesive effects of inhibiting LAT1 could be overcome by supplemental L-CSNO (S-nitroso-L-cysteine), but not D-CSNO or L-Cys, and suggest a basal anti-adhesive role for stereospecific intercellular SNO transport. This study reveals for the first time a novel role of LAT1 in the export of SNOs from RBCs to prevent their adhesion to ECs. The findings have implications for the mechanisms of intercellular SNO signalling, and for thrombosis, sickle cell disease, and post-storage RBC transfusion, when RBC adhesivity is increased.
Asunto(s)
Sistema de Transporte de Aminoácidos L/antagonistas & inhibidores , Sistema de Transporte de Aminoácidos L/sangre , Células Endoteliales/fisiología , Eritrocitos/efectos de los fármacos , Eritrocitos/fisiología , Sistema de Transporte de Aminoácidos L/genética , Aminoácidos Cíclicos/farmacología , Animales , Benzoxazoles/farmacología , Adhesión Celular/efectos de los fármacos , Adhesión Celular/fisiología , Cisteína/análogos & derivados , Cisteína/farmacología , Células Endoteliales/efectos de los fármacos , Deformación Eritrocítica/efectos de los fármacos , Deformación Eritrocítica/fisiología , Células Endoteliales de la Vena Umbilical Humana , Humanos , Técnicas In Vitro , Leucina/farmacología , Ratones , Ratones Desnudos , ARN Mensajero/sangre , ARN Mensajero/genética , Reticulocitos/fisiología , S-Nitrosotioles/sangre , S-Nitrosotioles/farmacología , Tirosina/análogos & derivados , Tirosina/farmacologíaRESUMEN
Erythrocyte deformability is an important property of erythrocytes that considerably affects blood flow and hemodynamics. The high content of polyphenols present in dark chocolate has been reported to play a protective role in functionality of erythrocytes. We hypothesized that chocolate might influence erythrocytes not only after repeated chronic intake, but also immediately after its ingestion. Thus, we determined the acute effect of dark chocolate and milk (with lower content of biologically active substances) chocolate intake on erythrocyte deformability. We also focused on selected factors that may affect erythrocyte deformability, specifically nitric oxide production in erythrocytes and total antioxidant capacity of plasma. We determined posttreatment changes in the mentioned parameters 2hours after consumption of chocolate compared with their levels before consumption of chocolate. In contrast to milk chocolate intake, the dark chocolate led to a significantly higher increase in erythrocyte deformability. Nitric oxide production in erythrocytes was not changed after dark chocolate intake, but significantly decreased after milk chocolate. The plasma total antioxidant capacity remained unaffected after ingestion of both chocolates. We conclude that our hypothesis was confirmed. Single ingestion of dark chocolate improved erythrocyte deformability despite unchanged nitric oxide production and antioxidant capacity of plasma. Increased deformability of erythrocytes may considerably improve rheological properties of blood and thus hemodynamics in humans, resulting in better tissue oxygenation.
Asunto(s)
Cacao/química , Chocolate , Deformación Eritrocítica/efectos de los fármacos , Eritrocitos/efectos de los fármacos , Hemodinámica/efectos de los fármacos , Preparaciones de Plantas/farmacología , Polifenoles/farmacología , Adulto , Animales , Antioxidantes/metabolismo , Antioxidantes/farmacología , Dieta , Ingestión de Alimentos , Eritrocitos/fisiología , Femenino , Humanos , Masculino , Leche , Óxido Nítrico/sangre , Preparaciones de Plantas/administración & dosificación , Valores de Referencia , Adulto JovenRESUMEN
BACKGROUND/AIMS: The main purpose of the present study was to investigate the effects of vitamin C and E supplements on the antioxidant capacity of erythrocytes obtained from young and aged rats. METHODS: Male Wistar rats aged 3 and 24 months were used. Vitamins C and E were injected at doses of 200 mg/kg (day) intraperitoneally in young and aged groups. The antioxidant capacity, oxidant stress parameters, and deformability of red blood cells collected from different age stages were evaluated. An in vitro oxidation system was constructed to explore the mechanisms of antioxidant capacity change in the vitamin treatment groups. RESULTS: Treatment with vitamins C and E can effectively restore the antioxidant capacity and deformability of red blood cells (RBCs) in aged rats. Under in vitro oxidative conditions, an age-dependent decline in the influx rate of L-cysteine was observed. This was significantly improved following treatment with vitamins C and E. CONCLUSION: We present evidence of an improvement in the antioxidant capacity of RBCs by treatment with vitamins C and E in aged rats. These observations also suggest that treatment with vitamins C and E improves glutathione synthesis by enhancing the influx rate of L-cysteine through the modification of membrane proteins and lipids.
Asunto(s)
Envejecimiento/fisiología , Antioxidantes/farmacología , Ácido Ascórbico/farmacología , Suplementos Dietéticos , Eritrocitos/fisiología , Vitamina E/farmacología , Animales , Cisteína/farmacología , Deformación Eritrocítica/efectos de los fármacos , Eritrocitos/efectos de los fármacos , Glutatión/metabolismo , Masculino , Oxidantes/toxicidad , Estrés Oxidativo/efectos de los fármacos , Ratas WistarRESUMEN
Experiments on rats with diabetes mellitus model induced by streptosotocin and high (30%) fat diet showed that the daily treatment with aqueous extracts of great nettle leaves (100 mg/kg) and common burdock roots (25 mg/kg) for a period of 10 days led to a decrease in the glycemic index and triglyceride level and produced protective action on erythrocytes both in animals kept on a fat-rich diet and on the background of a low-caloric ration. Both medicinal plant extracts were comparable with reference drug metformin in reducing the concentration of glycosylated hemoglobin (by 12-31%) and ectoglobular hemoglobin (1.7-1.8 times, p <0.05), decreasing the content of malonic dialdehyde in erythrocytes (1.3 times, p < 0.05), and increasing erythrocyte deformability (1.3-1.4 times, p < 0.05) and activity of their antioxidant enzymes glutathione peroxidase, glutathione reductase, glutathione-S-transferase, catalase, and supe- roxide dismutase (1.2-2.6 times, p < 0.05). A diet with usual (8%) fat content improved the metabolic indices to a lower degree (on the average by 13-21%, p < 0.05) than did the proposed phytotherapy.
Asunto(s)
Arctium/química , Diabetes Mellitus Experimental/tratamiento farmacológico , Hipoglucemiantes/farmacología , Fitoterapia/métodos , Extractos Vegetales/farmacología , Urtica dioica/química , Animales , Animales no Consanguíneos , Catalasa/metabolismo , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Dieta Alta en Grasa , Deformación Eritrocítica/efectos de los fármacos , Eritrocitos/efectos de los fármacos , Eritrocitos/metabolismo , Femenino , Glutatión Peroxidasa/metabolismo , Glutatión Reductasa/metabolismo , Glutatión Transferasa/metabolismo , Hipoglucemiantes/química , Metformina/farmacología , Extractos Vegetales/química , Plantas Medicinales , Ratas , Federación de Rusia , Estreptozocina , Superóxido Dismutasa/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismoRESUMEN
Measurements of red blood cell (RBC) deformability together with estimation of NO-synthase activity and Na,K-ATPase activity were used for characterization of RBC functionality in rats subjected to single dose of Escherichia coli lipopolysaccharides (LPS) at a dose of 1âmg/kg. We hypothesized that LPS might initiate a malfunction of RBC. We also investigated the potential effect of carotenoids (10âmg/kg/day) produced in red yeast biomass of Rhodotorula glutinis on RBC in LPS-challenged rats. LPS significantly reduced the deformability of RBC (by 14%) together with decrease of NO-synthase activity by 20%. Daily supplementation of carotenoids for 10 days attenuated the LPS-induced injury, as observed by 22% increase of RBC deformability and 23% increase of NO-synthase activity. The activity of Na,K-ATPase was also improved probably due to increased number of active enzyme molecules as indicated by 66% enhancement of Vmax value, hence maintaining the activity of erythrocyte Na,K-ATPase to the level even higher as compared with healthy control animals. It may be concluded that administration of yeast biomass with high content of carotenoids resulted in advanced function of erythrocytes as concerns their ability to squeeze through narrow capillaries of the circulation, better intrinsic production of NO and improvement of intracellular homeostasis of sodium.
Asunto(s)
Carotenoides/metabolismo , Eritrocitos/efectos de los fármacos , Lipopolisacáridos/metabolismo , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Animales , Biomasa , Modelos Animales de Enfermedad , Deformación Eritrocítica/efectos de los fármacos , Lipopolisacáridos/farmacología , Masculino , Óxido Nítrico , Ratas , LevadurasRESUMEN
BACKGROUND: Postmenopausal women often develop hemorheological disorders which may affect the systemic blood circulation and present a cardiovascular risk factor. OBJECTIVE: We evaluated effects of secoisolariciresinol (SECO), a phytoestrogen, on hemorheological parameters and lipid peroxidation in a model of the age-related and/or surgical menopause induced by ovariectomy in rats. METHODS: Arterial blood was sampled from sham-operated female rats, ovariectomized rats (OVX), and OVX treated with SECO (OVXSECO) (20 mg/kg/day intragastrically for two weeks). Plasma estrogen concentration and the following hemorheological parameters were measured: RBC aggregation (half-time of aggregation, T1/2; amplitude of aggregation, AMP; aggregation index, AI), RBC deformability (elongation index, EI), whole blood viscosity at the shear rate of 3-300 s-1, plasma viscosity, hematocrit, plasma fibrinogen. Lipid peroxidation was evaluated by measuring conjugated dienes (CD) and thiobarbituric acid reactive substances (TBARS) in plasma. RESULTS: Ovariectomy in rats caused a 60% decrease in plasma estrogen level and triggered the development of macro- and microhemorheological abnormalities. Blood viscosity increased by 12-31%, RBC elongation index reduced by 16-28%, and T1/2 and AI increased by 35% and 29% respectively. The increase in blood viscosity correlated predominantly with reduced RBC deformability. Plasma CD and TBARS were elevated by 47% and 104% respectively. SECO therapy for OVX rats reduced blood viscosity by 9-18% and T1/2 by 32%, and increased EI by 4-17%. SECO therapy disrupted the correlation between blood viscosity and RBC deformability. Lipid peroxidation was significantly inhibited, as shown by the reduction in CD and TBARS plasma concentrations by 89% and 70% respectively. SECO did not affect plasma viscosity, estrogen or fibrinogen levels. CONCLUSIONS: SECO treatment for OVX rats improves blood macro- and microrheological parameters, possibly through antioxidant protection of RBC.
Asunto(s)
Viscosidad Sanguínea/efectos de los fármacos , Butileno Glicoles/farmacología , Agregación Eritrocitaria/efectos de los fármacos , Deformación Eritrocítica/efectos de los fármacos , Hemorreología/efectos de los fármacos , Lignanos/farmacología , Ovariectomía/efectos adversos , Fitoestrógenos/farmacología , Animales , Estradiol/sangre , Femenino , Hematócrito , Peroxidación de Lípido/efectos de los fármacos , Ovario/cirugía , Ratas , Ratas WistarRESUMEN
Chinese dragon's blood, the red resin of Dracaena cochinchinensis, one of the renowned traditional medicines, has been used to facilitate blood circulation and disperse blood stasis for thousands of years. Phenolic compounds are considered to be responsible for its main biological activities. In this study, total phenolic compounds of Chinese dragon's blood were made into capsule (Longxuetongluo Capsule, LTC) and their effects on the abnormal hemorheological properties were examined by high fat diet (HFD) induced ApoE-/- mice. Compared to the model group, LTC recovered the abnormal hemorheological parameters in HFD-induced ApoE-/- mice by reducing whole blood viscosity (WBV) at high rate and improving erythrocyte function. In conclusion, LTC could ameliorate erythrocyte deformability and osmotic fragility through the reduction of lipid peroxidation on plasma and erythrocyte membranes in HFD-induced ApoE-/- mice, which supported the traditional uses of Chinese dragon's blood as an effective agent for improving blood microcirculation in hypercholesterolemia.
Asunto(s)
Apolipoproteínas E/deficiencia , Grasas de la Dieta/efectos adversos , Deformación Eritrocítica/efectos de los fármacos , Eritrocitos/metabolismo , Hipercolesterolemia , Preparaciones de Plantas/farmacología , Animales , Cápsulas , Grasas de la Dieta/farmacología , Hipercolesterolemia/sangre , Hipercolesterolemia/inducido químicamente , Hipercolesterolemia/tratamiento farmacológico , Hipercolesterolemia/genética , Medicina Tradicional China , RatonesRESUMEN
The aim of the present study was to test the effects of Pfaffia paniculata (PP) extract on the red blood cell (RBC) rheological properties of patients with sickle cell disease (SCD) and healthy (AA) individuals. Blood from 7 SCD and 4 AA individuals were collected in EDTA tubes. Washed RBCs were incubated with various concentration of PP extract: 0.0, 0.2 or 0.5âmg/ml of PP solution for 5âhrs at 37°C. RBC deformability was measured by ektacytometry at 9 shear stresses ranging from 0.3 to 30âPa, and RBC aggregation properties were determined by laser-backscattered techniques. Because RBCs from SCD patients are fragile, a stability test was also performed to test for the fragility of RBC exposed to a constant shear stress (70âPa) for 10âmin. While RBC deformability was not improved by the use of PP extract in AA, we noted an improvement of this parameter in patients with SCD between the 0.0 and 0.5âmg/ml conditions. In contrast to AA RBCs, the fragility of SCD RBCs was not affected by PP extract. In conclusion, this study demonstrates the beneficial effects, in-vitro, of PP extract on the RBC deformability of SCD patients, notably at high shear stress (a shear stress condition usually found in capillaries).