Research on the impact of zinc chloride complexes on the hemostasis system and blood rheological characteristics

Lebedeva S. А.
Doctor of Biological Sciences, professor of Department of Pharmacology, A.P. Neljubin Institute of Pharmacy¹, professor of Department of Medical Elementology²
ORCID: 0000-0001-8769-1040

Babasieva V. S.
graduate student of Department of Pharmacology, A.P. Neljubin Institute of Pharmacy¹
ORCID: 0000-0003-2846-4133

Ponomarev A. V.
graduate student of Department of Pharmacology, A.P. Neljubin Institute of Pharmacy¹
ORCID: 0009-0000-9966-703X

Rylina Е. V.
Ph.D. of Pharmaceutical Sciences associate professor of Department of Medical Elementology²
ORCID 0000-0002-9375-309X

Samorodov А. V.
Doctor of Medical Sciences professor of Department of Pharmacology¹, A.P. Neljubin Institute of Pharmacy³
ORCID: 0000-0001-9302-499X

1Sechenov First Moscow State Medical University (Sechenov University) Trubetskaya St., 8-2, Moscow, 119991, Russian Federation
2Peoples’ Friendship University of Russia (RUDN University), Miklukho-Maklaya St., 6, Moscow, 117198, Russian Federation
3Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, st. Petrovka, 25, building 2, 107031, Moscow, Russian Federation

Lebedeva Svetlana; e-mail: lebedeva502@yandex.ru

None declared.

Fundamental scientific research No. FGWS-2025-0008 «Hypoxia in critical conditions – leading mechanisms of development, personalized diagnostics and treatment.».

30.01.2026

02.04.2026

Introduction. Zinc is a key cofactor of many enzymes and regulatory proteins, affecting hemostasis, blood rheology and microcirculation processes, while its deficiency and excess modify thrombosis and blood fluidity in different ways. Zinc complex compounds with N-alkenylimidazoles have previously demonstrated antihypoxic, anti-inflammatory and wound healing properties, which led to the study of their effect on the hemostasis system and microcirculation. Objective of the study: to evaluate the effect of zinc chloride complexes with N-alkenylimidazoles on the hemostasis system and blood rheology parameters. Material and methods. Zinc chloride complex compounds (Acizol-Cl, Allyl-Cl, Allyl-2-Cl, Propargyl-Cl) were studied in comparison with acetylsalicylic acid (ASA), pentoxifylline, and heparin in vitro on the blood of healthy donors and in vivo on male rats. Platelet aggregation, P-selectin (CD62P) expression, coagulogram parameters, microhemodynamic parameters, and tissue oxygenation were evaluated using laser flowmetry, optical oxygenation, and wavelet analysis of blood flow fluctuations. Results. Zinc chloride complexes prolonged activated partial thromboplastin time (APTT) without changing prothrombin time (PV) and fibrinogen levels, while Allyl-Cl and Allyl-2-Cl showed pronounced antiplatelet activity comparable to ASA with a more significant increase in the latency period of aggregation. All complexes almost completely suppressed platelet activation (CD62P expression), and Allyl-Cl and Allyl-2-Cl improved microcirculation, increasing perfusion and flux, enhancing oxygen utilization and efficiency of oxygen metabolism, as well as increasing the amplitudes of neurogenic, myogenic, and pulse fluctuations in blood flow. Conclusion. Zinc chloride complex compounds, N alkenylimidazole derivatives, have a combination of antiplatelet and mild anticoagulant effects with improved microcirculation and tissue oxygenation. Allyl derivatives (Allyl-Cl, Allyl-2-Cl) are of particular interest as potential agents for the prevention and treatment of thrombosis and conditions accompanied by microcirculatory and hypoxic disorders, which requires further preclinical and clinical studies. 

zinc, hemostasis, zinc complexes, microcirculation, microhemodynamics, oxygenation, P-selectin

10.29234/2308-9113-2026-14-2-146-161

1. Shakhmardanova SA, Galenko-Yaroshevsky PA. Metal complex compounds of zinc with N-alkenylimidazoles: biological activity and application in medicine (review). Sechenov Bull. 2016;(3):84-90.

2. Annamaraju P, Patel P, Baradhi KM. Pentoxifylline. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. [updated 2024 Feb 29; cited 2026 Apr 15]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK559096/.

3. Ishida T, Saido M, Saitama S. Thrombosis prevention and anti-thrombus formation by zinc (II) ions against COVID-19 infection. J Clin Case Rep Stud. 2022;3(6). doi: 10.31579/2690-8808/114.

4. Broderick C, Forster R, Abdel-Hadi M, Salhiyyah K. Pentoxifylline for intermittent claudication. Cochrane Database Syst Rev. 2020;10(10):CD005262. doi:10.1002/14651858.CD005262.pub4.

5. Chaudhry SA, Serrata M, Tomczak L, et al. Cationic zinc is required for factor XII recruitment and activation by stimulated platelets and for thrombus formation in vivo. J Thromb Haemost. 2020;18(9):2318-2328. doi:10.1111/jth.14964.

6. Erken G, Küçükatay MB, Turgut S, et al. The Effects of Electromagnetic Fields Generated from 1800 MHz Cell Phones on Erythrocyte Rheological Parameters and Zinc Level in Rats. Balkan Med J. 2012;29(2):139-143. doi:10.5152/balkanmedj.2011.021.

7. Galenko-Yaroshevsky PA, Shelemekh OV, Popkov VL, Zadorozhniy AV, Nektarevskaya IB, Bunyatyan ND, et al. Study of the anti-inflammatory, analgesic, ulcerogenic and anti-ulcerogenic activity of N-isopropenylimidazole zinc complex derivative. Research Results in Pharmacology. 2024;10(1):23-43. doi: 10.18413/rrpharmacology.10.443

8. Khaled S, Brun JF, Cassanas G, Bardet L, Orsetti A. Effects of zinc supplementation on blood rheology during exercise. Clin Hemorheol Microcirc. 1999;20(1):1-10. PMID: 11185677.

9. Lebedeva S, Galenko-Yaroshevsky P, Fateeva T, Pashin S, Pashina N, Nektarevskaya I, et al. Effective wound healing agents based on N-alkenylimidazole zinc complexes derivatives: future prospects and opportunities. Res Results Pharmacol. 2023;9(3):27-39. doi: 10.18413/rrpharmacology.9.10047.

10. Lebedeva S, Galenko-Yaroshevsky P, Trofimov B, Parshina L, Shelemekh O, Sergeeva A, et al. Zinc-dependent mechanisms of reparative regeneration: theoretical aspects and translational perspectives. Rev Clin Pharmacol Drug Ther. 2025;23(2):105-118. doi: 10.17816/RCF660184.

11. Mammadova-Bach E, Braun A. Zinc Homeostasis in Platelet-Related Diseases. Int J Mol Sci. 2019;20(21):5258. doi:10.3390/ijms20215258.

12. Ornelas A, Zacharias-Millward N, Menter DG, Davis JS, Lichtenberger L, Hawke D, et al. Beyond COX-1: the effects of aspirin on platelet biology and potential mechanisms of chemoprevention. Cancer Metastasis Rev. 2017;36(2):289-303. doi: 10.1007/s10555-017-9675-z.

13. Parshina L, Grishchenko L, Smirnov V, Borodina T, Shakhmardanova S, Tarasov V, et al. Synthesis, characterization and biological evaluation of Zn(II) and Co(II) complexes of N-allylimidazole as potential hypoxia-targeting agents. Polyhedron. 2019;161:126-131. doi: 10.1016/j.poly.2019.01.005.

14. Patel P, Huang D. Heparin. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. [Updated 2025 Aug 9; cited 2026 Apr 15]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK538247/

15. Seirafianpour F, Mozafarpoor S, Fattahi N, Sadeghzadeh-Bazargan A, Hanifiha M, Goodarzi A. Treatment of COVID-19 with pentoxifylline: Could it be a potential adjuvant therapy?. Dermatol Ther. 2020;33(4):e13733. doi:10.1111/dth.13733.

16. Sobczak AIS, Pitt SJ, Stewart AJ. Influence of zinc on glycosaminoglycan neutralisation during coagulation. Metallomics. 2018;10(9):1180-1190. doi:10.1039/c8mt00159f.

17. Vu TT, Fredenburgh JC, Weitz JI. Zinc: an important cofactor in haemostasis and thrombosis. Thromb Haemost. 2013;109(3):421-430. doi:10.1160/TH12-07-0465.

18. Wen WX, Lee SY, Siang R, Koh RY. Repurposing Pentoxifylline for the Treatment of Fibrosis: An Overview. Adv Ther. 2017;34(6):1245-1269. doi:10.1007/s12325-017-0547-2

19. Heyns Adu P, Eldor A, Yarom R, Marx G. Zinc-induced platelet aggregation is mediated by the fibrinogen receptor and is not accompanied by release or by thromboxane synthesis. Blood. 1985 Jul;66(1):213-9. PMID: 2988668.

20. Marx G, Krugliak J, Shaklai M. Nutritional zinc increases platelet reactivity. Am J Hematol. 1991;38(3):161-165. doi:10.1002/ajh.2830380302.

21. Kuropatkin AI. The importance of oscillatory processes in the diagnosis of the state of microcirculatory tissue systems. Hum Physiol. 2018;44(5):103-114. doi: 10.1134/S0131164618050077.

22. Krupatkin AI, Sidorov VV, editors. Laser Doppler flowmetry of blood microcirculation [Internet]. Moscow: OJSC «Medicine» Publishing House; 2005. (Avalible at: https://lazma.ru/rus/article.php?r=101&d=217 (cited by: 30.01.2026)