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. 2024 Jun 20;29(12):2941.
doi: 10.3390/molecules29122941.

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

Krzysztof Gwozdzinski  1 , Stella Bujak-Pietrek  2 , Anna Pieniazek  1 , Lukasz Gwozdzinski  3
Affiliations

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

Krzysztof Gwozdzinski et al. Molecules. .

Abstract

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.

Keywords: catalase; lactate dehydrogenase; nitroxide; oxidative stress; red blood cells; superoxide dismutase.

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Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1
Chemical structures of piperidine (Tempo (1), Tempol (2), and Tempamine (3)), pyrroline (Pyrrolin (4) and Carboxy-Pyrrolin (5)); and pyrrolidine (Pyrrolid (6) and Carboxy-Pyrrolid (7)) nitroxides.
Figure 2
Figure 2
Values of total glutathione concentration (GSH + GSSG) in RBCs after treatment with various concentrations of nitroxides, including (A) six-membered nitroxides, and (B) five-membered nitroxides. The results are presented as percentage changes compared to the control, the value of which was taken as 100% (n = 9).
Figure 3
Figure 3
The levels of ascorbic acid in RBCs after treatment with five-membered nitroxide radicals. The results are presented as percentage changes compared to the control, the value of which was taken as 100% (n = 8). (* significantly different in comparison to the control at least at p < 0.05).
Figure 4
Figure 4
The thiol group concentrations in membrane proteins at various concentrations of tested piperidine (A), pyrroline, and pyrrolidine (B) nitroxides. The obtained results are presented as mean with standard deviation (n = 8). (* significantly different in comparison to the control at least p < 0.05).
Figure 5
Figure 5
The thiol group concentration in hemolysate proteins at various concentrations of tested piperidine (A), pyrroline, and pyrrolidine (B) nitroxides. Results shown include mean ± SD values (n = 8). (* significantly different in comparison to the control at least p < 0.05).
Figure 6
Figure 6
The activity of superoxide dismutase in human RBCs treated with different concentrations of nitroxides. The results presented are mean ± SD values (n = 10). (* significantly different in comparison to the control at least p < 0.05).
Figure 7
Figure 7
Catalase activity in RBC lysates after their previous treatment with various concentrations of penta-fronted nitroxides. The results presented are mean ± SD values (n = 10).
Figure 8
Figure 8
Lactate dehydrogenase activity determined in RBCs after their treatment with pentameric nitroxides. The results presented are mean ± SD values (n = 7).
Figure 9
Figure 9
Changes in the content of MetHb relative to the total hemoglobin pool after treatment of RBCs with nitroxides. The results presented are mean MetHb ± SD of concentrations (n = 8). (* significantly different in comparison to the control at least at p < 0.05).
Figure 10
Figure 10
Assessment of the degree of lipid peroxidation in RBCs after treatment with increasing concentrations of nitroxides. The obtained results (mean values ± SD) were calculated with the control, the value of which was taken as 100% (n = 8).
Figure 11
Figure 11
Assessment of the degree of oxidative damage to proteins (level of carbonyl groups) in RBCs after their treatment with nitroxides derived from pyrroline and pyrrolidine. The presented results are the average ± SD of 8 independent measurements.
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