Effect of new chalcone analogues on hemostasis in animals with experimental «сytokine storm»: 616-002:616.151.55
Тромбоз, гемостаз и реология

Tromboz, Gemostaz I Reologiya
scientific and practical journal

ISSN 2078–1008 (Print); ISSN 2687-1483 (online)

Keywords

chalcone analogues
«cytokine storm»
coagulopathy
hypercytokinemia

Abstract

Summary. Background. «Cytokine storm» is a disorder of the immune system with severe hypecytokinemia, characterized by the development of coagulation disorders with a high level of mortality. Objectives: to evaluate the effect of new chalcone analogues on changes of hemostasis reactions in rats under the conditions of an experimental «cytokine storm». Materials/Methods. The study was performed on 80 male Wistar rats divided into 8 equal groups of 10 individuals. The «cytokine storm» was modeled in animals by intraperitoneal injection of lipopolysaccharide at a dose of 10 mg/kg. The test-compounds at a dose of 20 mg/kg intraperitoneally and the reference drug — heparin (20 U/kg, subcutaneously) were administered 60 minutes after the pathology simulation. After 24 hours, the serum levels of fibrinogen, D-dimer, soluble fibrin-monomer complexes, antithrombin III activity, thrombin time, and the degree of ADP-stimulated platelet aggregation were evaluated in rats. Results. The study showed that the use of chalcone analogues contributed to the restoration of hemostasis reactions, which was expressed in a decrease in the concentration of fibrinogen, D-dimer, soluble fibrin-monomer complexes, the degree of platelet aggregation, and an increase in antithrombin III activity and thrombin time. At the same time, among the studied substances, the compound containing hydroxyl in the 2nd position and the methyl group in the 5th position showed a slightly higher level of pharmacological activity than the other test compounds. Conclusions. Based on the obtained data, it is actuality to assume the relevance of further study of chal- cone analogues as agents that normalize hemostasis in hypercytokine disorders.

References:

  1. Fajgenbaum D. C., June C. H. Cytokine storm. N Engl J Med. 2020;383(23):2255–73. DOI: 10.1056/NEJMra2026131. 

  2. Miesbach W., Makris M. COVID-19: Coagulopathy, risk of thrombo- sis, and the rationale for anticoagulation. Clin Appl Thromb Hemost. 2020;26:1076029620938149. DOI: 10.1177/1076029620938149. 

  3. Klok F.A., Kruip M.J.H.A., van der Meer N.J.M. et al. Confirmation of the high cumulative incidence of thrombotic complications in critically ill ICU patients with COVID-19: an updated analysis. Thromb Res. 2020;191:145–47. DOI: 10.1016/j.thromres.2020.04.041. 

  4. Zhou F., Yu T., Du R. et al. Clinical course and risk factors for mor- tality of adult in patients with COVID-19 in Wuhan, China: a ret- rospective cohort study. Lancet. 2020;395(10229):1054–62. DOI: 10.1016/S0140–6736(20)30566–3. 

  5. Gudima G.O., Khaitov R.M., Kudlay D.A., Khaitov M.R. Molecu- lar immunological aspects of diagnostics, prevention and treat- ment of coronavirus infection. Immunologiya. 2021;42(3):198– 210. (In Russ.). DOI: 10.33029/0206–4952–2021–42–3–198–210. 

  6. Guo H., Sheng Y., Li W. et al. Coagulopathy as a prodrome of cyto- kine storm in COVID-19-infected patients. Front Med (Lausanne). 2020;7:572989. DOI: 10.3389/fmed.2020.57298. 

  7. Asakura H., Ogawa H. COVID-19-associated coagulopathy and dis- seminated intravascular coagulation. Int J Hematol. 2021;113(1):45– DOI: 10.1007/s12185–020–03029-y. 

  8. Gomes M.N., Muratov E.N., Pereira M. et al. Chalcone deriva- tives: promising starting points for drug design. Molecules. 2017;22(8):1210. DOI: 10.3390/molecules22081210. 

  9. Ohkura N., Ohnishi K., Taniguchi M. et al. Anti-platelet effects of chalcones from Angelica keiskei Koidzumi (Ashitaba) in vivo. Pharmazie. 2016;71(11):651–4. DOI: 10.1691/ph.2016.6678.
  10. Torbati D. Heparin effects during hyperbaric oxygenation in rats. Life Sci. 1985;36(2):147–51. DOI: 10.1016/0024–3205(85)90093–1.
  11. Pozdnyakov D.I., Voronkov A.V., Rukovitsyna V.M. Chromon-3-al- dehyde derivatives restore mitochondrial function in rat cerebral Iran J Basic Med Sci. 2020;23(9):1172–83. DOI: 10.22038/ijbms.2020.46369.10710.
  12. Zhang H., Sha J., Feng X. et al. Dexmedetomidine ameliorates LPS induced acute lung injury via GSK-3β/STAT3-NF-κB signa- ling pathway in rats. Int Immunopharmacol. 2019;74:105717. DOI: 10.1016/j.intimp.2019.105717.
  13. Gabbasov Z.A., Popov E.G., Gavrilov I. Yu. A new highly sensitive method for analyzing platelet aggregation. Laboratornoe delo. 1989;(10):15–8. (In Russ.).
  14. England J.T., Abdulla A., Biggs C.M. et al. Weathering the COVID-19 storm: Lessons from hematologic cytokine syndromes. Blood Rev. 2021;45:100707. DOI: 10.1016/j.blre.2020.100707.
  15. Adelusi T.I., Akinbolaji G.R., Yin X. et al. Neurotrophic, anti-neu- roinflammatory, and redox balance mechanisms of chalcones. Eur J Pharmacol. 2021;891:173695. DOI: 10.1016/j.ejphar.2020.173695.
  16. Joseph L., Fink L.M., Hauer-Jensen M. Cytokines in coagula- tion and thrombosis: a preclinical and clinical review. Blood Coagul Fibrinolysis. 2002;13(2):105–16. DOI: 10.1097/00001721– 200203000–00005.
  17. van der Poll T., de Jonge E., Levi M. Regulatory role of cytokines in disseminated intravascular coagulation. Semin Thromb Hemost. 2001;27(6):639–51. DOI: 10.1055/s-2001–18868.