Microrheological responses of red blood cells of different ages to the hydrogen sulfide donor, sodium hydrosulfide and the substrate of its endogenous synthesis, L-cysteine

Article type: Research Article

Authors: Muravyov, A.^{a; *} | Tikhomirova, I.^a | Priezzhev, A.^b | Lugovtsov, A.^b | Volkova, A.^a

Affiliations: [a] State Pedagogical University, Yaroslavl, Russia | [b] State University, Moscow, Russia

Correspondence: [*] Corresponding author: A.V. Muravyov, State Pedagogical University, Yaroslavl, Russia. Tel.: +79010526717; E-mail: [email protected].

Abstract: BACKGROUND:There are red blood cells (RBCs) of different ages in the circulating blood. At the same time, old cells have reduced deformability and increased RBC aggregability. With an increase in the number of old RBCs, especially in pathology, this can significantly affect tissue oxygenation. It is known that the gaseous mediators: nitric oxide (NO) and hydrogen sulfide (H2S) have a positive effect on the RBC microrheology and quite possibly differently on old and young red blood cells. OBJECTIVE:The purpose of this research work was to study the capabilities of the H2S donor and substrate of its endogenous production, L-cysteine to change positively the microrheological characteristics of RBCs of different ages to varying degrees. METHODS:Whole blood samples (9 mL) from healthy donors (n = 24) were drawn vacuum tubes. RBCs were separated from plasma by centrifugation and washed three times. Red blood cells were density fractionated, according to the method described by Murphy and were separated into three main age subpopulations by Percoll density gradient centrifugation. RBCs of all three age fractions were incubated for 30 min. at 37°C with: NaHS (100 μM), L-cysteine (500 μM), clotrimazole as Gardos channel blocker (50 μM). After RBC incubation, their deformability (RBCD) and aggregation (RBCA) were recorded and compared with the corresponding cell suspension to which the drug was not added. RESULTS:The results of the study showed that both compounds NaHS and L-cysteine moderately and significantly increased RBCD in all age subpopulations of RBCs and significantly reduced aggregation. It was found that the magnitudes of these microrheological responses were significantly greater in old RBCs. Analysis of the results showed that Gardos channels may be one of the molecular targets for the action of H2S on red blood cells. CONCLUSION:Old RBCs significantly increased deformability and decreased aggregation than mature and young cells in response to exposure to NaHS or L-cysteine. In general, we can conclude that a donor of hydrogen sulfide and a substrate for its synthesis, L-cysteine can be considered as a promising drug for restoring impaired RBC microrheological characteristics and contribute to the preservation of the function of old RBCs.

Keywords: Red blood cell, red blood cell age subpopulations, deformability, aggregation, hydrogen sulphide, L-cysteine

DOI: 10.3233/JCB-249001

Journal: Journal of Cellular Biotechnology, vol. 10, no. 2, pp. 183-192, 2024