Beneficial Effect of Quercetin on Erythrocyte Properties in Type 2 Diabetic Rats

Diabetes mellitus is characterized by tissue oxidative damage and impaired microcirculation, as well as worsened erythrocyte properties. Measurements of erythrocyte deformability together with determination of nitric oxide (NO) production and osmotic resistance were used for the characterization of erythrocyte functionality in lean (control) and obese Zucker diabetic fatty (ZDF) rats of two age categories. Obese ZDF rats correspond to prediabetic (younger) and diabetic (older) animals. As antioxidants were suggested to protect erythrocytes, we also investigated the potential effect of quercetin (20 mg/kg/day for 6 weeks). Erythrocyte deformability was determined by the filtration method and NO production using DAF-2DA fluorescence. For erythrocyte osmotic resistance, we used hemolytic assay. Erythrocyte deformability and NO production deteriorated during aging—both were lower in older ZDF rats than in younger ones. Three-way ANOVA indicates improved erythrocyte deformability after quercetin treatment in older obese ZDF rats only, as it was not modified or deteriorated in both (lean and obese) younger and older lean animals. NO production by erythrocytes increased post treatment in all experimental groups. Our study indicates the potential benefit of quercetin treatment on erythrocyte properties in condition of diabetes mellitus. In addition, our results suggest potential age-dependency of quercetin effects in diabetes that deserve additional research

Ultra-Small Superparamagnetic Iron-Oxide Nanoparticles Exert Different Effects on Erythrocytes in Normotensive and Hypertensive Rats

We determined erythrocyte physiological and biochemical properties after the single and repeated administration of ultra-small superparamagnetic iron-oxide nanoparticles (USPIONs) in normotensive Wistar–Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Polyethylene glycol-coated USPIONs (transmission electron microscope detected a mean size of ~30 nm and hydrodynamic size ~51 nm) were intravenously administered to rats either in one infusion at nominal dose 1 mg Fe/kg or in two infusions (administered with a difference of 24 h) at nominal dose 2 mg Fe/kg. Results showed that USPIONs did not deteriorate erythrocyte deformability, nitric oxide production, and osmotic resistance in both experimental settings. Both the single and repeated USPION administration elevated erythrocyte deformability in WKY. However, this effect was not present in SHR; deformability in USPION-treated SHR was significantly lower than in USPION-treated WKY. Nitric oxide production by erythrocytes was increased after a single USPION treatment in WKY, so it can be associated with improvement in erythrocyte deformability. Using biomagnetometry, we revealed significantly lower amounts of USPION-originated iron in erythrocytes in SHR compared with WKY. We found a much faster elimination of USPIONs from erythrocytes in hypertensive rats compared with the normotensive ones, which might be relevant for clinical practice in hypertensive patients undergoing clinical examination with the use of iron-oxide nanoparticles

Effects of Taxifolin in Spontaneously Hypertensive Rats with a Focus on Erythrocyte Quality

Oxidative stress and multiple erythrocyte abnormalities have been observed in hypertension. We focused on the effects of angiotensin-converting enzyme 2 (ACE2) inhibition by MLN-4760 inhibitor on angiotensin peptides, oxidative stress parameters, and selected erythrocyte quality markers in spontaneously hypertensive rats (SHR). We also investigated the potential effects of polyphenolic antioxidant taxifolin when applied in vivo and in vitro following its incubation with erythrocytes. SHRs were divided into four groups: control, taxifolin-treated, MLN-4760-treated, and MLN-4760 with taxifolin. MLN-4760 administration increased the blood pressure rise independent of taxifolin treatment, whereas taxifolin decreased it in control SHRs. Body weight gain was also higher in ACE2-inhibited animals and normalized after taxifolin treatment. However, taxifolin did not induce any change in angiotensin peptide concentrations nor a clear antioxidant effect. We documented an increase in Na,K-ATPase enzyme activity in erythrocyte membranes of ACE2-inhibited SHRs after taxifolin treatment. In conclusion, ACE2 inhibition deteriorated some selected RBC properties in SHRs. Although taxifolin treatment did not improve oxidative stress markers, our data confirmed the blood pressure-lowering potential, anti-obesogenic effect, and some “erythroprotective” effects of this compound in both control and ACE2-inhibited SHRs. In vitro investigations documenting different effects of taxifolin on erythrocyte properties from control and ACE2-inhibited SHRs accentuated the irreplaceability of in vivo studies

Monocrotaline-Induced Pulmonary Arterial Hypertension and Bosentan Treatment in Rats: Focus on Plasma and Erythrocyte Parameters

The objective of our study was to contribute to the characterization of monocrotaline-induced pulmonary arterial hypertension (PAH) in a rat model, with emphasis on the renin–angiotensin–aldosterone system, parameters of oxidative stress, the activity of matrix metalloproteinases, and erythrocyte parameters. Moreover, we aimed to analyze the effects of bosentan. Experiments were performed on 12-week-old male Wistar rats randomly assigned to 3 groups: control, monocrotaline-treated (60 mg/kg), and monocrotaline combined with bosentan (300 mg/kg/day). Our study confirmed the well-known effects of monocrotaline administration on lungs and the right ventricle, as well as pulmonary arterial pressure. In addition, we observed activation of the alternative pathway of the renin–angiotensin system, namely an increase in angiotensin (Ang) 1–7 and Ang 1-5 together with an increase in Ang I, but without any change in Ang II level, and downregulation of aldosterone 4 weeks after monocrotaline administration. For the first time, modifications of erythrocyte Na,K-ATPase enzyme kinetics were demonstrated as well. Our observations do not support data obtained in PAH patients showing an increase in Ang II levels, increase in oxidative stress, and deterioration in RBC deformability. Although bosentan primarily targets the vascular smooth muscle, our study confirmed its antioxidant effect. The obtained data suggest that besides the known action of bosentan, it decreases heart rate and increases erythrocyte deformability, and hence could have a beneficial hemodynamic effect in the PAH condition

Angiotensin System Modulations in Spontaneously Hypertensive Rats and Consequences on Erythrocyte Properties; Action of MLN-4760 and Zofenopril

Various pathologies (COVID-19 including) are associated with abnormalities in erythrocyte properties. Hypertension represents an unfavorable condition for erythrocyte quality and is the most prevalent risk factor in COVID-19 patients. ACE2 downregulation that is typical of these patients can further deteriorate cardiovascular health; however, its consequences on erythrocyte properties are not known yet. The aim was to investigate the effect of ACE2 inhibition and the potential beneficial effect of zofenopril on erythrocytes in spontaneously hypertensive rats. ACE2 inhibition induced by MLN-4760 (1 mg/kg/day for 2 weeks) led to deterioration of erythrocyte morphology and osmotic resistance, but plasma markers of oxidative stress, erythrocyte deformability, nitric oxide production and Na,K-ATPase activity were not significantly affected. Zofenopril administration (10 mg/kg/day, initiated after 4-day-lasting ACE2 inhibition) resulted in unexpected increase in angiotensin II plasma levels in both control and ACE-inhibited spontaneously hypertensive rats, but in normalization of osmotic resistance in ACE2-inhibited rats. The overall effect of zofenopril on erythrocyte qualities could be evaluated as beneficial

Alterations in Oxidative Stress Markers and Na,K-ATPase Enzyme Properties in Kidney after Fructose Intake and Quercetin Intervention in Rats

The study aimed to characterize the consequences of a 15-week intake of 10% fructose on the kidney, with the focus on oxidative stress markers and properties of the Na,K-ATPase enzyme. Various antioxidants naturally occurring in common food were demonstrated to be protective against fructose-induced deterioration of kidneys. Therefore, we also aimed to observe the effect of 6-week quercetin administration (20 mg/kg/day) that was initiated following the 9-week period of higher fructose intake, by determining the concentration of sodium, potassium, creatinine, urea, and glucose in blood plasma and oxidative status directly in the renal tissue. Kinetic studies of renal Na,K-ATPase were utilized for a deeper insight into the molecular principles of expected changes in this enzyme activity under conditions of presumed fructose-induced renal injury. Fructose intake led to increase in body weight gain, plasma glucose and sodium levels, and deterioration of kidney properties, although some compensatory mechanisms were observable. Quercetin administration improved glycemic control in rats exposed to fructose overload. However, an increase in plasma creatinine, a decrease in GSH/GSSG ratio in renal tissue homogenate, and a controversial effect on renal Na,K-ATPase enzyme suggest that quercetin treatment may not be beneficial in the condition of pre-existing renal pathology