Factors Influencing Venous Remodeling in the Development of Varicose Veins of the Lower Limbs.

One of the early symptoms of chronic venous disease (CVD) is varicose veins (VV) of the lower limbs. There are many etiological environmental factors influencing the development of chronic venous insufficiency (CVI), although genetic factors and family history of the disease play a key role. All these factors induce changes in the hemodynamic in the venous system of the lower limbs leading to blood stasis, hypoxia, inflammation, oxidative stress, proteolytic activity of matrix metalloproteinases (MMPs), changes in microcirculation and, consequently, the remodeling of the venous wall. The aim of this review is to present current knowledge on CVD, including the pathophysiology and mechanisms related to vein wall remodeling. Particular emphasis has been placed on describing the role of inflammation and oxidative stress and the involvement of extracellular hemoglobin as pathogenetic factors of VV. Additionally, active substances used in the treatment of VV were discussed.

Acrolein Induces Changes in Cell Membrane and Cytosol Proteins of Erythrocytes.

High concentrations of acrolein (2-propenal) are found in polluted air and cigarette smoke, and may also be generated endogenously. Acrolein is also associated with the induction and progression of many diseases. The high reactivity of acrolein towards the thiol and amino groups of amino acids may cause damage to cell proteins. Acrolein may be responsible for the induction of oxidative stress in cells. We hypothesized that acrolein may contribute to the protein damage in erythrocytes, leading to the disruption of the structure of cell membranes. The lipid membrane fluidity, membrane cytoskeleton, and osmotic fragility were measured for erythrocytes incubated with acrolein for 24 h. The levels of thiol, amino, and carbonyl groups were determined in cell membrane and cytosol proteins. The level of non-enzymatic antioxidant potential (NEAC) and TBARS was also measured. The obtained research results showed that the exposure of erythrocytes to acrolein causes changes in the cell membrane and cytosol proteins. Acrolein stiffens the cell membrane of erythrocytes and increases their osmotic sensitivity. Moreover, it has been shown that erythrocytes treated with acrolein significantly reduce the non-enzymatic antioxidant potential of the cytosol compared to the control.

Modulation of the Human Erythrocyte Antioxidant System by the 5- and 6-Membered Heterocycle-Based Nitroxides.

Nitroxides are stable radicals consisting of a nitroxyl group, >N-O•, which carries an unpaired electron. This group is responsible for the paramagnetic and antioxidant properties of these compounds. A recent study evaluated the effects of pyrrolidine and pyrroline derivatives of nitroxides on the antioxidant system of human red blood cells (RBCs). It showed that nitroxides caused an increase in the activity of superoxide dismutase (SOD) and the level of methemoglobin (MetHb) in cells (in pyrroline derivatives) but had no effect on the activity of catalase and lactate dehydrogenase. Nitroxides also reduced the concentration of ascorbic acid (AA) in cells but did not cause any oxidation of proteins or lipids. Interestingly, nitroxides initiated an increase in thiols in the plasma membranes and hemolysate. However, the study also revealed that nitroxides may have pro-oxidant properties. The drop in the AA concentration and the increase in the MetHb level and in SOD activity may indicate the pro-oxidant properties of nitroxides in red blood cells.

Baicalin and Baicalein Enhance Cytotoxicity, Proapoptotic Activity, and Genotoxicity of Doxorubicin and Docetaxel in MCF-7 Breast Cancer Cells.

Breast cancer is a major health concern and the leading cause of death among women worldwide. Standard treatment often involves surgery, radiotherapy, and chemotherapy, but these come with side effects and limitations. Researchers are exploring natural compounds like baicalin and baicalein, derived from the Scutellaria baicalensis plant, as potential complementary therapies. This study investigated the effects of baicalin and baicalein on the cytotoxic, proapoptotic, and genotoxic activity of doxorubicin and docetaxel, commonly used chemotherapeutic drugs for breast cancer. The analysis included breast cancer cells (MCF-7) and human endothelial cells (HUVEC-ST), to assess potential effects on healthy tissues. We have found that baicalin and baicalein demonstrated cytotoxicity towards both cell lines, with more potent effects observed in baicalein. Both flavonoids, baicalin (167 µmol/L) and baicalein (95 µmol/L), synergistically enhanced the cytotoxic, proapoptotic, and genotoxic activity of doxorubicin and docetaxel in breast cancer cells. In comparison, their effects on endothelial cells were mixed and depended on concentration and time. The results suggest that baicalin and baicalein might be promising complementary agents to improve the efficacy of doxorubicin and docetaxel anticancer activity. However, further research is needed to validate their safety and efficacy in clinical trials.

The Effect of Piperidine Nitroxides on the Properties of Metalloproteins in Human Red Blood Cells.

Nitroxides are stable, low molecular-weight radicals containing a nitroxide group that has an unpaired electron. The presence of a nitroxide group determines their redox properties. The effect of the piperidine nitroxides, Tempo, Tempol, and Tempamine, on metalloproteins (hemoglobin, superoxide dismutase, catalase) and lactate dehydrogenase in red blood cells was investigated in this research. In addition, the level of lipid peroxidation and the level of protein carbonyl groups were examined as indicators of the effect of oxidative stress. Nitroxides increased superoxide dismutase activity and oxidized hemoglobin to methemoglobin, and also slightly decreased the catalase activity of red blood cells treated with nitroxides. Tempol significantly decreased lactate dehydrogenase activity. All three nitroxides had no effect on membrane lipid peroxidation and protein oxidation. Our results confirm that nitroxides have both antioxidant and prooxidative effects in human red blood cells. The piperidine nitroxides do not initiate the oxidation of proteins and lipids in the membranes of human red blood cells.

Diosmin and Bromelain Stimulate Glutathione and Total Thiols Production in Red Blood Cells.

Diosmin and bromelain are bioactive compounds of plant origin with proven beneficial effects on the human cardiovascular system. We found that diosmin and bromelain slightly reduced total carbonyls levels and had no effect on TBARS levels, as well as slightly increased the total non-enzymatic antioxidant capacity in the RBCs at concentrations of 30 and 60 µg/mL. Diosmin and bromelain induced a significant increase in total thiols and glutathione in the RBCs. Examining the rheological properties of RBCs, we found that both compounds slightly reduce the internal viscosity of the RBCs. Using the MSL (maleimide spin label), we revealed that higher concentrations of bromelain led to a significant decrease in the mobility of this spin label attached to cytosolic thiols in the RBCs, as well as attached to hemoglobin at a higher concentration of diosmin, and for both concentrations of bromelain. Both compounds tended to decrease the cell membrane fluidity in the subsurface area, but not in the deeper regions. An increase in the glutathione concentration and the total level of thiol compounds promotes the protection of the RBCs against oxidative stress, suggesting that both compounds have a stabilizing effect on the cell membrane and improve the rheological properties of the RBCs.

Indoxyl Sulfate Induces Oxidative Changes in Plasma and Hemolysate.

The deteriorating function of the kidneys in chronic kidney disease (CKD) is associated, among other things, with the retention of many unnecessary metabolic products in the body. Indoxyl sulfate (IS) belongs to the group of uremic toxins with a high protein binding affinity. Moreover, this compound can generate oxidative stress. We hypothesized that a high concentration of IS might induce oxidative changes in erythrocytes and plasma components, and could therefore contribute to CKD progression. In this study, we evaluated the influence of IS on the oxidative stress parameters in plasma and hemolysate. Moreover, as a result of the action of IS, we observed a decrease in the total antioxidant capacity and a change in the activity of catalase and superoxide dismutase in hemolysate and plasma. The obtained results indicate that IS induces oxidative damage to hemolysate and plasma components. Greater changes in the parameters of oxidative stress were observed in hemolysate than in plasma treated with indoxyl sulfate. The obtained results suggest that the increased concentration of IS in patients with chronic kidney disease may lead to a decrease in the lifespan of erythrocytes in their bloodstream.

Uremic Toxins and Their Relation with Oxidative Stress Induced in Patients with CKD.

The presence of toxins is believed to be a major factor in the development of uremia in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). Uremic toxins have been divided into 3 groups: small substances dissolved in water, medium molecules: peptides and low molecular weight proteins, and protein-bound toxins. One of the earliest known toxins is urea, the concentration of which was considered negligible in CKD patients. However, subsequent studies have shown that it can lead to increased production of reactive oxygen species (ROS), and induce insulin resistance in vitro and in vivo, as well as cause carbamylation of proteins, peptides, and amino acids. Other uremic toxins and their participation in the damage caused by oxidative stress to biological material are also presented. Macromolecules and molecules modified as a result of carbamylation, oxidative stress, and their adducts with uremic toxins, may lead to cardiovascular diseases, and increased risk of mortality in patients with CKD.

Indoxyl Sulfate Generates Free Radicals, Decreases Antioxidant Defense, and Leads to Damage to Mononuclear Blood Cells.

Indoxyl sulfate (IS) is a uremic toxin that has been associated with inflammation and oxidative stress as well as with the progression of chronic kidney disease (CKD). IS is a protein metabolite that is concentrated in the serum of CKD patients. IS is a well-known uremic toxin, but there are very few reports on the effect of IS on cells including mononuclear cells (MNCs). We hypothesized that a high concentration of IS in CKD patients may induce changes in redox balance in the in vitro cells exposed. In the present study, we investigated the effect of IS on free radical production, antioxidant capacity, and protein damage in the mononuclear blood cells. As already determined, the concentrations (0.2 or 1 mM) of IS used in this study do not affect the survival rate of MNCs. For both the concentrations of IS, there was an increase in superoxide and nitric oxide and a release of other reactive oxygen species (ROS) inside the cells, as measured using fluorescent probes. However, an increase in other ROS as indicated by H2DCF-DA was found only for 1 mM of IS. Moreover, a decrease in the non-enzymatic antioxidant capacity and an increase in the superoxide dismutase activity after incubation of the cells with IS were observed. Furthermore, we found an increase in the levels of carbonyl compounds and peroxides in the cells treated with both the concentrations of IS. The obtained results show that IS induces oxidative stress and a decrease in antioxidant defense in cells leading to lipid and protein damage.

Inhibitory effect of silver nanoparticles on proliferation of estrogen-dependent MCF-7/BUS human breast cancer cells induced by butyl paraben or di-n-butyl phthalate.

In this study the effect of silver nanoparticles (AgNPs) on proliferation of estrogen receptor (ER)-positive human breast cancer MCF-7/BUS cells was assessed by means of in vitro assay. The cells were exposed in the absence of estrogens to AgNPs alone or in combination with aluminum chloride (AlCl3), butyl paraben (BPB) and di-n-butyl phthalate (DBPh). The results revealed that AgNPs at the non-cytotoxic concentrations (up to 2µg/mL) and AlCl3 (up to 500µM) did not induce proliferation of MCF-7/BUS cells whereas BPB and DBPh showed strong estrogenic activity with the highest effect at 16µM and 35µM, respectively. AgNPs inhibited the proliferation of the cells induced by DBPh, BPB or even with 17ß-estradiol (E2) during 6-day incubation in the absence of estrogens. ICI 182,780 (10nM), a known estrogen receptor (ER) antagonist, induced strong inhibitory effect. AgNPs also decreased transcription of the estrogen-responsive pS2 and progesterone receptor (PGR) genes but modulated expression neither of ERα nor ERß in MCF-7/BUS cells exposed to BPB, DBPh or E2 for 6h. Our results indicate that AgNPs may inhibit growth of breast cancer cells stimulated by E2 or estrogenic chemicals, i.e. BPB and DBPh.

Investigation of oxidative stress parameters in different lifespan erythrocyte fractions in young untrained men after acute exercise.

NEW FINDINGS: What is the central question of this study? What is the influence of a single bout of exercise on the properties of erythrocyte fractions at different ages? What is the main finding and its importance? A single bout of exercise in untrained men induced oxidative stress in erythrocytes and had an influence on antioxidant defense in these cells. Old erythrocytes were more sensitive to oxidative damage than young and middle-aged cells. Higher levels of glutathione in old erythrocyte fractions did not protect them against oxidative stress. It seems that exercise may promote the removal of old erythrocytes from the circulation. The objective of this study was to establish the role of exercise-induced oxidative stress in the erythrocyte fractions [young (YF), middle-aged (MAF) and old (OF)] of young untrained men after acute exercise. Blood samples were collected before exercise, immediately after and 1 h after exercise. The maximal power generated was 292 ± 27 W, and exercise duration was 8.73 ± 0.9 min. Different optical properties and oxidative stress parameters were found in each erythrocyte fraction. Total thiols in YF and MAF after exercise and after 1 h rest were similar to values before exercise; however, in OF {32.7 ± 9.8 nmol [mg haemoglobin (Hb)]-1 } the concentration was lower in comparison to YF [55.5 ± 3.2 nmol (mg Hb)-1 ] and MAF [56.8 ± 7.7 nmol (mg Hb)-1 ] and increased 1 h later (P < 0.0002). The glutathione concentration was higher in OF [8.4 ± 0.4 nmol (mg Hb)-1 ] than in YF [4.5 ± 0.6 nmol (mg Hb)-1 ] and MAF [4.8 ± 0.5 nmol (mg Hb)-1 ; P < 0.0002] and did not change after exercise or 1 h later. In OF, the peroxide level was higher after exercise [1.2 ± 0.2 nmol (mg Hb)-1 ] and 1 h later [1.1 ± 0.2 nmol (mg Hb)-1 ], when compared with samples before exercise [0.9 ± 0.1 nmol (mg Hb)-1 ; P < 0.05]. Similar results were observed in YF and MAF. The level of thiobarbituric acid reactive substances (TBARS) was ∼2.5-fold higher in OF [0.19 ± 0.04 nmol (mg Hb)-1 ] when compared with YF [0.07 ± 0.01 nmol (mg Hb)-1 ] and MAF [0.08 ± 0.02 nmol (mg Hb)-1 ; P < 0.0002] and was increased after exercise, remaining unchanged 1 h later. In YF and MAF, no difference in the level of TBARS was detected after exercise or 1 h later. No difference in membrane fluidity was observed in all fractions. The erythrocyte OF appeared to be more sensitive to cellular oxidative damage.

Inhibition of glutamate receptors reduces the homocysteine-induced whole blood platelet aggregation but does not affect superoxide anion generation or platelet membrane fluidization.

Homocysteine (Hcy) is an excitotoxic amino acid. It is potentially possible to prevent Hcy-induced toxicity, including haemostatic impairments, by antagonizing glutaminergic receptors. Using impedance aggregometry with arachidonate and collagen as platelet agonists, we tested whether the blockade of platelet NMDA (N-methyl-D-aspartate), AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) and kainate receptors with their inhibitors: MK-801 (dizocilpine hydrogen maleate, [5R,10S]-[+]-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine), CNQX (7-nitro-2,3-dioxo-1,4-dihydroquinoxaline-6-carbonitrile) and UBP-302 (2-{[3-[(2S)-2-amino-2-carboxyethyl]-2,6-dioxo-3,6-dihydropyrimidin 1(2H)-yl]methyl}benzoic acid) may hamper Hcy-dependent platelet aggregation. All the tested compounds significantly inhibited Hcy-augmented aggregation of blood platelets stimulated either with arachidonate or collagen. Hcy stimulated the generation of superoxide anion in whole blood samples in a concentration-dependent manner; however, this process appeared as independent on ionotropic glutamate receptors, as well as on NADPH oxidase and protein kinase C, and was not apparently associated with the extent of either arachidonate- or collagen-dependent platelet aggregation. Moreover, Hcy acted as a significant fluidizer of surface (more hydrophilic) and inner (more hydrophobic) regions of platelet membrane lipid bilayer, when used at the concentration range from 10 to 50 µmol/l. However, this effect was independent on the Hcy action through glutamate ionotropic receptors, since there was no effects of MK-801, CNQX or UBP-302 on Hcy-mediated membrane fluidization. In conclusion, Hcy-induced changes in whole blood platelet aggregation are mediated through the ionotopic excitotoxic receptors, although the detailed mechanisms underlying such interactions remain to be elucidated.

[Carbamylation of proteins--mechanism, causes and consequences]. / Karbamylacja bialek--mechanizm, przyczyny i skutki.

Carbamylation (carbamoylation) is a post-translational modification resulting from the nonenzymatic reaction between isocyanic acid and free functional groups of proteins, in particular with the free amino groups. This reaction alters structural and functional properties of proteins and results in faster aging of proteins. Urea present in the body can be transformed into cyanate and its more reactive form, isocyanic acid. High concentration of urea is associated with some diseases, especially with chronic renal failure and atherosclerosis. In human tissues, urea and cyanate are in equilibrium in aqueous solutions. Surprisingly, concentration of isocyanate in the body is much lower than it would appear from the kinetic parameters of urea decomposition. The low concentration of isocyanic acid results from its high reactivity and short half-life. In this review we describe the biochemical mechanism of carbamylation of proteins and free amino acids. We summarize the literature data for carbamylation of hemoglobin, lipoproteins, albumin, membrane proteins and erythropoietin in chronic renal failure. In summary, the carbamylation of proteins may have a negative impact on their biological activity and may contribute to the deterioration of patients with chronic renal failure.

Quercetin attenuates oxidative stress in the blood plasma of rats bearing DMBA-induced mammary cancer and treated with a combination of doxorubicin and docetaxel.

The development of side-effects during doxorubicin-docetaxel (DOX-DTX) chemotherapy is considered as related to generation of oxidative stress by DOX. The addition of docetaxel potentiates this effect. Thus, antioxidants are assumed as a promising remedy for neutralizing deteriorating effects of reactive oxygen species (ROS) in pathological conditions and polyphenolic antioxidants are suitable candidates for such a therapeutic approach. We evaluated the ability of quercetin to attenuate oxidative stress developed during the process of DMBA carcinogenesis and DOX-DTX chemotherapy in the blood plasma of rats bearing mammary tumors. We have found that quercetin significantly improved the plasma nonenzymatic antioxidant capacity (NEAC) and reduced lipid peroxidation, which suggest the beneficial effect of flavonoid. The inclusion of quercetin to the DOX-DTX chemotherapy was also advantageous. A considerable decrease of carbonyls and lipid peroxidation products (TBARS) and improvement of the endogenous antioxidant defense system (an increase of NEAC, thiols and SOD activity) were observed compared to rats treated with DOX-DTX chemotherapy. These results suggest that quercetin could protect blood plasma constituents against oxidative damage evoked by DOX and DTX.

Alterations in red blood cells and plasma properties after acute single bout of exercise.

The aim of this study was to investigate alterations in haemoglobin conformation and parameters related to oxidative stress in whole erythrocytes, membranes, and plasma after a single bout of exercise in a group of young untrained men. Venous blood samples from eleven healthy young untrained males (age = 22 ± 2 years, BMI = 23 ± 2.5 kg/m(2)) were taken from the antecubital vein before an incremental cycling exercise test, immediately after exercise, and 1 hour after exercise. Individual heart rate response to this exercise was 195 ± 12 beats/min and the maximum wattage was 292 ± 27 W. Immediately after exercise, significant increase in standard parameters (haemoglobin, haematocrit, lactate levels, and plasma volume) of blood was observed as well as plasma antioxidant capacity one hour after exercise. Reversible conformational changes in haemoglobin, measured using a maleimide spin label, were found immediately following exercise. The concentration of ascorbic acid inside erythrocytes significantly decreased after exercise. A significant decline in membrane thiols was observed one hour after exercise, but simultaneously an increase in plasma thiols immediately after and 1 h after exercise was also observed. This study shows that a single bout of exercise can lead to mobilization of defensive antioxidant systems in blood against oxidative stress in young untrained men.

Indoxyl sulfate induces apoptosis in mononuclear blood cells via mitochondrial pathway.

The consequence of chronic kidney disease is the accumulation of metabolic products called uremic toxins in the body. Indoxyl sulfate (IS) is a toxin with a high affinity for proteins. This study focuses on the deleterious effect of IS, especially apoptosis induction, in mononuclear blood cells (MNCs). Thus, in MNCs treated with IS at three different concentrations for 24 h, the survival, mitochondrial potential, caspases activity and expression, Bcl-2 and Bax protein expression, DNA damage, and PARP degradation were estimated. The study showed a decrease in survival and mitochondrial potential of MNCs treated with IS compared to the control. IS increased the activity of caspase 2-, 3-, 9-, and the expression of caspase 3-, and 9- in MNCs but does not affect the activity of caspase 6- and 8. The treatment of MNCs with IS also increased DNA damage and degradation of PARP. Indoxyl sulfate significantly influences the expression of Bcl-2 and Bax proteins. Indoxyl sulfate induces the programmed death of MNCs through the intrinsic mitochondrial apoptotic pathway. The observed cellular changes are mostly dose-dependent.

The Effect of Diosmin, Escin, and Bromelain on Human Endothelial Cells Derived from the Umbilical Vein and the Varicose Vein-A Preliminary Study.

In this study, we investigated the properties of human varicose vein (VV) endothelial cells (HVVEC) in comparison to the human umbilical vein endothelial cells (HUVEC). The cells were treated with three bioactive compounds with proven beneficial effects in the therapy of patients with VV, diosmin, escin, and bromelain. Two concentrations of tested drugs were used (1, 10 mg/mL), which did not affect the viability of either cell type. Escin led to a slight generation of reactive oxygen species in HUVEC cells. We observed a slight release of superoxide in HVVEC cells upon treatment with diosmin and escin. Diosmin and bromelain showed a tendency to release nitric oxide in HUVEC. Using membrane fluorescent probes, we demonstrated a reduced fluidity of HVVEC, which may lead to their increased adhesion, and, consequently, a much more frequent occurrence of venous thrombosis. For the first time, we show the mechanism of action of drugs used in VV therapy on endothelial cells derived from a VV. Studies with HVVEC have shown that tested drugs may lead to a reduction in the adhesive properties of these cells, and thus to a lower risk of thrombosis.

Cytotoxic effects in 3T3-L1 mouse and WI-38 human fibroblasts following 72 hour and 7 day exposures to commercial silica nanoparticles.

The potential toxic effects in murine (3T3-L1) and human (WI-38) fibroblast cell lines of commercially available silica nanoparticles (NPs), Ludox CL (nominal size 21 nm) and CL-X (nominal size of 30 nm) were investigated with particular attention to the effect over long exposure times (the tests were run after 72 h exposure up to 7 days). These two formulations differed in physico-chemical properties and showed different stabilities in the cell culture medium used for the experiments. Ludox CL silica NPs were found to be cytotoxic only at the higher concentrations to the WI-38 cells (WST-1 and LDH assays) but not to the 3T3-L1 cells, whereas the Ludox CL-X silica NPs, which were less stable over the 72 h exposure, were cytotoxic to both cell lines in both assays. In the clonogenic assay both silica NPs induced a concentration dependent decrease in the surviving fraction of 3T3-L1 cells, with the Ludox CL-X silica NPs being more cytotoxic. Cell cycle analysis showed a trend indicating alterations in both cell lines at different phases with both silica NPs tested. Buthionine sulfoximine (γ-glutamylcysteine synthetase inhibitor) combined with Ludox CL-X was found to induce a strong decrease in 3T3-L1 cell viability which was not observed for the WI-38 cell line. This study clearly indicates that longer exposure studies may give important insights on the impact of nanomaterials on cells. However, and especially when investigating nanoparticle effects after such long exposure, it is fundamental to include a detailed physico-chemical characterization of the nanoparticles and their dispersions over the time scale of the experiment, in order to be able to interpret eventual impacts on cells.

Structural component changes of erythrocytes caused by oxidative stress generated by indoxyl sulfate.

Indoxyl sulfate (IS) belongs to groups of uremic toxins binding to proteins. This compound may contribute to the generation of oxidative stress in chronic kidney disease (CKD) patients. We hypothesized that a high concentration of IS in the blood may induce structural changes of erythrocyte components and thus may contribute to CKD progression. In the present study, we evaluated the influence of IS on hemolysate and membrane proteins' conformational state, lipid membrane fluidity, and internal viscosity in erythrocytes. We examined thiols, carbonyl groups, peroxides, and TBARS levels in erythrocyte incubated with IS. The treatment of erythrocytes with IS led to increase in lipid membrane fluidity, decrease in the internal viscosity of the cells and the motion of the spin labels attached to hemolysate proteins. We did not observe conformational changes in plasma membrane proteins; however, in the plasma membranes of erythrocytes incubated with IS, a decrease in the content of thiol groups and increase in the carbonyls levels and peroxides and TBARS in comparison with the control was observed. The obtained results indicate that IS induces the oxidative damage of erythrocyte components. This may be an important factor that affects the functional properties of erythrocytes in CKD patients.

Reactive Oxygen Species and Their Involvement in Red Blood Cell Damage in Chronic Kidney Disease.

Reactive oxygen species (ROS) released in cells are signaling molecules but can also modify signaling proteins. Red blood cells perform a major role in maintaining the balance of the redox in the blood. The main cytosolic protein of RBC is hemoglobin (Hb), which accounts for 95-97%. Most other proteins are involved in protecting the blood cell from oxidative stress. Hemoglobin is a major factor in initiating oxidative stress within the erythrocyte. RBCs can also be damaged by exogenous oxidants. Hb autoxidation leads to the generation of a superoxide radical, of which the catalyzed or spontaneous dismutation produces hydrogen peroxide. Both oxidants induce hemichrome formation, heme degradation, and release of free iron which is a catalyst for free radical reactions. To maintain the redox balance, appropriate antioxidants are present in the cytosol, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and peroxiredoxin 2 (PRDX2), as well as low molecular weight antioxidants: glutathione, ascorbic acid, lipoic acid, α-tocopherol, ß-carotene, and others. Redox imbalance leads to oxidative stress and may be associated with overproduction of ROS and/or insufficient capacity of the antioxidant system. Oxidative stress performs a key role in CKD as evidenced by the high level of markers associated with oxidative damage to proteins, lipids, and DNA in vivo. In addition to the overproduction of ROS, a reduced antioxidant capacity is observed, associated with a decrease in the activity of SOD, GPx, PRDX2, and low molecular weight antioxidants. In addition, hemodialysis is accompanied by oxidative stress in which low-biocompatibility dialysis membranes activate phagocytic cells, especially neutrophils and monocytes, leading to a respiratory burst. This review shows the production of ROS under normal conditions and CKD and its impact on disease progression. Oxidative damage to red blood cells (RBCs) in CKD and their contribution to cardiovascular disease are also discussed.