Fullerenol C60(OH)36 Protects the Antioxidant Enzymes in Human Erythrocytes against Oxidative Damage Induced by High-Energy Electrons

Abstract

Ionizing radiation (IR) can pass through the human body easily, potentially causing severe damage to all biocomponents, which is associated with increasing oxidative stress. IR is employed in radiotherapy; however, in order to increase safety, it is necessary to minimize side effects through the use of radioprotectors. Water-soluble derivatives of fullerene exhibit antiradical and antioxidant properties, and these compounds are regarded as potential candidates for radioprotectors. We examined the ability of fullerenol C60(OH)36 to protect human erythrocytes, including the protection of the erythrocytal antioxidant system against high-energy electrons. Human erythrocytes irradiated with high-energy [6 MeV] electrons were treated with C60(OH)36 (150 µg/mL), incubated and haemolyzed. The radioprotective properties of fullerenol were determined by examining the antioxidant enzymes activity in the hemolysate, the concentration of -SH groups, as well as by determining erythrocyte microviscosity. The irradiation of erythrocytes (650 and 1300 Gy) reduces the number of thiol groups; however, an attenuation of this harmful effect is observed (p < 0.05) in the presence of C60(OH)36. Although no significant effect of fullerenol was recorded on catalase activity, which was preserved in both control and test samples, a more active protection of other enzymes was evident. An irradiation-induced decrease in the activity of glutathione peroxidase and glutathione reductase became an increase in the activity of those two enzymes in samples irradiated in the presence of C60(OH)36 (p < 0.05 and p < 0.05, respectively). The fourth studied enzyme, glutathione transferase, decreased (p < 0.05) its activity in the irradiated hemolysate treated with C60(OH)36, thus, indicating a lower level of ROS in the system. However, the interaction of fullerenol with the active centre of the enzyme cannot be excluded. We also noticed that radiation caused a dose-dependent decrease in the erythrocyte microviscosity, and the presence of C60(OH)36 reduced this effect (p < 0.05). Overall, we point to the radioprotective effect of C60(OH)36 manifested as the protection of the antioxidant enzymes of human erythrocytes against IR-induced damage, which has not been the subject of intense research so far.

Atomic Force Microscopy and High-Resolution Spectrophotometry for Study of Anoxemia and Normoxemia in Model Experiment In Vitro

“…The mechanism of changes in RBCs under hypoxemia/anoxemia and hyperoxemia in comparison with normoxemia is based primarily on the ratio of oxidative/antioxidant system performance under these conditions [ 68 ]. An imbalance between oxidant and antioxidant systems leads to oxidative stress, that is, to a sharp increase of ROS [ 70 ].…”

“…Under these conditions, redox imbalance increases compared to normoxemia [ 58 ]. If there is an imbalance between the production of ROS in biological systems and their ability to defend themselves with a complex antioxidant system, then oxidative stress occurs, leading to structural disorders in cells [ 68 ]. The underlying mechanisms of hypoxemia-induced injury and understanding of the response of RBCs to deoxygenation and hypoxemia are still discussed in a number of studies [ 22 ].…”

Mechanochemical Synergism of Reactive Oxygen Species Influences on RBC Membrane

“…Analysis of the influence of ROS must also consider their wide range of influences on biological objects, in particular, the cell membrane. To study oxidative stress, RBCs are often used as a research model [ 34 , 35 ]. Moreover, such analyses must take into account that the most active ROS that influences lipids in RBC membranes is radical [ 36 ].…”

Kinetics of Metallofullerenol Reactions with the Products of Water Radiolysis: Implications for Radiotherapeutics

“…Erythrocytes are also a biophysical model for studying membrane changes under the influence of ionizing radiation 36,37 and are ideal models for studies of protecting agents in radiotherapy. 19,38 ■ RESULTS AND DISCUSSION Characterization of Metallofullerenols. Three MFs presented in Scheme 1 were synthesized from commercially available metallofullerenes, Lu 3 N@C 80 , Sc 3 N@C 80 , and Gd@ C 82 , using the modified method reported by Shinohara et al 10 as described in the Experimental Section.…”

“…The above ROS are also generated during normal metabolic processes in cells of all aerobic organisms, and their overproduction is responsible for oxygen toxicity in biological systems undergoing oxidative stress. − The rate constants for ROS reduction can be considered as descriptors of antioxidant activity; however, the effectiveness and mechanisms of action of radical trapping antioxidants depend also on their interactions and localization at the lipid/water interphase, which is particularly important in biologically relevant systems. − In our studies, we used erythrocytes (red blood cells, RBC) as a unique and convenient biological model that can be employed to gain knowledge about the mechanisms of antioxidant action of small molecules and nanoparticles. Erythrocytes are also a biophysical model for studying membrane changes under the influence of ionizing radiation , and are ideal models for studies of protecting agents in radiotherapy. , …”