Experimental estimation of the effects of exogenous carbon monoxide on blood cells

The aim of the study was to investigate the effect of the carbon monoxide (CO) donor on the Ca2+-activated potassium permeability of the erythrocyte membrane and platelet aggregation ability.

Materials and methods. Healthy volunteers (n = 27) and patients with chronic coronary heart disease (CHD) (n = 32) of both sexes were examined. The material of the study was packed red blood cells and platelet-rich plasma obtained from patient’s venous blood. The change of Ca2+-dependent potassium conductivity of the erythrocyte membrane was evaluated by potentiometric method, and the platelet aggregation was studied by turbidimetric method. Carbon monoxide releasing molecule-2 (CORM-2) was used as a CO donor. The amplitude of A23187- and redox-induced hyperpolarization response (HR) of erythrocytes, and the rate and degree of platelet aggregation were estimated.

Results. It was shown that the addition of CORM-2 (10 and 100 μM) in the erythrocyte suspension caused a dose-dependent decrease in the amplitude of A23187- and redox-dependent HR in healthy donors, as well as in patients with chronic CHD. The maximum decrease was observed in the presence of 100 μM CORM-2. The effect of CORM-2 at concentrations of 10 and 100 μM on collagen-induced platelet aggregation led to a decrease in the degree and rate of aggregation in healthy donors. The maximum effect was shown at 100 μM of CO donor. However, such an unambiguous effect of CORM-2 on the aggregation parameters in patients with CHD was not observed.

Conclusion. The results suggest that CO has a significant effect on the ion transport function of the erythrocyte membrane and platelet aggregation activity of both healthy donors and patients with CHD.

1. Garcia‐Gallego S., Bernardes G. Carbon‐monoxide‐releasing molecules for the delivery of therapeutic CO in vivo. Angew. Chem. Int. Ed. Engl. 2014; 53 (37): 9712–9721. DOI: 10.1002/anie.201311225.

2. Lang E., Qadri S.M., Jilani K., Zelenak C., Lupescu A., Schleicher E., Lang F. Carbon monoxide-sensitive apoptotic death of erythrocytes. Basic Clin. Pharmacol. Toxicol. 2012; 111 (5): 348–355. DOI: 10.1111/j.1742-7843.2012.00915.x.

3. Ryter S.W., Choi A.M. Heme oxygenase−1/carbon monoxide: from metabolism to molecular therapy. Am. J. Respir. Cell. Mol. Biol. 2009; 41 (3): 251–260.

4. Motterlini R., Otterbein L.E. The therapeutic potential of carbon monoxide. Nat. Rev. Drug. Discov. 2010; 9 (9): 728–743. DOI: 10.1038/nrd3228.

5. Tyunina O.I., Artyukhov V.G. Carbon monoxide (CO) modulates surface architectonics and energy metabolism of human blood erythrocytes. Bull. Exp. Biol. Med. 2018; 165 (6): 803–807. DOI: 10.1007/s10517-018-4269-5.

6. Revin V.V., Ushakova A.A., Gromova N.V., Balykova L.A., Revina E.S., Stolyarova V.V., Stolbova T.A., Solomadin I.N., Tychkov A.Yu., Revina N.V., Imarova O.G. Study of erythrocyte indices, erythrocyte morphometric indicators, and oxygen-binding properties of hemoglobin hematoporphyrin patients with cardiovascular diseases. Adv. Hematol. 2017; 2017: 8964587. DOI: 10.1155/2017/8964587.

7. Upadhyay R.K. Emerging risk biomarkers in cardiovascular diseases and disorders. J. Lipids. 2015; 2015: 971453. DOI: 10.1155/2015/971453.

8. Tziakas D.N., Kaski J.C., Chalikias G.K., Romero C., Fredericks S., Tentes I.K., Kortsaris A.X., Hatseras D.I., Holt D.W. Total cholesterol content of erythrocyte membranes is increased in patients with acute coronary syndrome: a new marker of clinical instability? J. Am. Coll. Cardiol. 2007; 49 (21): 2081–2089. DOI: 10.1016/j.jacc.2006.08.069.

9. Namazi G., Jamshidi R.S., Attar A.M., Sarrafzadegan N., Sadeghi M., Naderi G., Pourfarzam M. Increased membrane lipid peroxidation and decreased Na+/K+-ATPase activity in erythrocytes of patients with stable coronary artery disease. Coron. Artery Dis. 2015; 26 (3): 239–244. DOI: 10.1097/MCA.0000000000000196.

10. Thomas S.L., Bouyer G., Cueff A., Egee S., Glogowska E., Ollivaux C. Ion channels in human red blood cell membrane: Actors or relics? Blood Cells, Molecules & Diseases. 2011; 46 (4): 261–265. DOI: 10.1016/j.bcmd.2011.02.007.

11. Maher A.D., Kuchel P.W. The Gаrdos channel: a review of the Ca2+-activated K+ channel in human erythrocytes. Int. J. Biochem. Cell Biol. 2003; 35 (8): 1182–1197. DOI: 10.1016/S1357-2725(02)00310-2.

12. Chlopicki S., Lomnicka M., Fedorowicz A., Grochal E., Kramkowski K., Mogielnicki A., Buczko W., Motterlini R. Inhibition of platelet aggregation by carbon monoxide-releasing molecules (CO-RMs): comparison with NO donors. Naunyn-Schmiedeberg’s Arch. Pharmacol. 2012; 385 (6): 641–650. DOI: 10.1007/s00210-012-0732-4.

13. Gusakova S.V., Kovalev I.V., Birulina Y.G., Smagliy L.V., Petrova I.V., Nosarev A.V., Orlov S.N., Aleinyk A.N. The effects of carbon monoxide and hydrogen sulfide on transmembrane ion transport. Biophysics. 2017; 62 (2): 220–226. DOI: 10.1134/S0006350917020099.

14. Yun S.H., Sim E.H., Goh R.Y., Park J.I., Han J.Y. Platelet Activation: The Mechanisms and potential biomarkers. Biomed. Res. Int. 2016; 2016: 9060143. DOI: 10.1155/2016/9060143.

15. Шатурный В.И., Шахиджанов С.С., Свешникова А.Н., Пантелеев М.А. Активаторы, рецепторы и пути внутриклеточной сигнализации в тромбоцитах крови. Биомедицинская химия. 2014; 60 (2): 182–200.

16. Del Carlo B., Pellegrini M., Pellegrino M. Modulation of Ca2+-activated K+ channels of human erythrocytes by endogenous protein kinase C. Biochim. Biophys. Acta. 2003; 1612 (1): 107–116. DOI: 10.1016/S0005-2736(03)00111-1.

17. Metere A., Iorio E., Scorza G., Camerini S., Casella M., Crescenzi M., Minetti M., Pietraforte D. Carbon monoxide signaling in human red blood cells: evidence for pentose phosphate pathway activation and protein deglutathionylation. Antioxid Redox Signal. 2014; 20 (3): 403–416.

18. Петрова И.В., Бирулина Ю.Г., Трубачева О.А., Розенбаум Ю.А., Смаглий Л.В., Рыдченко В.С., Гусакова С.В. Участие SH-групп в регуляции Са2-зависимой калиевой проницаемости мембраны эритроцитов при сердечно-сосудистой патологии. Российский физиологический журнал им. И.М. Сеченова. 2018; 104 (7): 827–834. DOI: 10.7868/S0869813918070080.

19. Bratseth V., Pettersen A.A., Opstad T.B., Arnesen H., Seljeflot I. Markers of hypercoagulability in CAD patients. Effects of single aspirin and clopidogrel treatment. Thromb. J. 2012; 10 (1): 12. DOI: 10.1186/1477-9560-10-12.

20. Sharma D., Pandey M., Rishi J.P. A Study of platelet volume indices in patients of coronary artery diseases. Journal of Scientific and Innovative Research. 2016; 5 (5): 161–164.

21. McBane R.D., Karnicki K., Tahirkheli N., Miller R.S., Owen W.G. Platelet characteristics associated with coronary artery disease. J. Thromb Haemost. 2003; 1 (6): 1296–1303. DOI: 10.1046/j.1538-7836.2003.00183.x.

22. Schwartz K.A. Aspirin resistance: a clinical review focused on the most common cause, noncompliance. Neurohospitalist. 2011; 1 (2): 94–103. DOI: 10.1177/1941875210395776.