Viper snakebite is considered to be a serious and life-threatening medical problem due to its ability to cause various types of coagulopathies. The current study aimed to investigate the effects of Vipera berus berus and Vipera berus nikolskii venoms on hemostasis in rats. To determine the possible mechanisms of coagulopathy that occurred as a post-bite complication, various hemostatic parameters were studied in experimental animals 24 hours after a single intraperitoneal injection of V. b. berus or V. b. nikolskii venom. The obtained results were compared to those of the control group, composed of the rats not-treated with viper venom. Our results revealed the state of hypocoagulability in both groups of envenomed rats, which was accompanied by prolongation of plasma coagulation in the thrombin time test, reduction in plasma fibrinogen level, increased fibrin/fibrinogen degradation products, as well as functionally inactive prothrombin forms compared to the control. Both venoms also enhanced the heparin activity and inhibited the antithrombin III activity. Furthermore, severe alterations in fibrinolysis were noticed after venom injection. An increased level of plasmin activity was accompanied by a significant decrease in α-2-antiplasmin activity in the plasma of envenomed rats. It is concluded that V. b. berus and V. b. nikolskii venom toxins have significant effects on plasma coagulation and fibrinolysis and that viper snakebite could be an important risk factor for coagulopathy development.
Halenova T, Raksha N, Kostiuk O, Andriichuk T, Ahafonova L, Ahafonov K, Piliponova V, Maievskyi O, Savchuk O. Coagulopathy in the experimental rats elicited by Vipera berus berus or Vipera berus nikolskii envenomation. J Appl Pharm Sci. 2025. Online First. https://doi.org/10.7324/JAPS.2025.302657727
1. Oliveira AL, Viegas MF, da Silva SL, Soares AM, Ramos MJ, Fernandes PA. The chemistry of snake venom and its medicinal potential. Nat Rev Chem. 2022;6(7):451–69. doi: https://doi.org/10.1038/s41570-022-00393-7
2. Casewell NR, Jackson TNW, Laustsen AH, Sunagar K. Causes and consequences of snake venom variation. Trends Pharmacol. Sci. 2020;41(8):570–81. doi: https://doi.org/10.1016/j.tips.2020.05.006
3. Ferraz CR, Arrahman A, Xie C, Casewell NR, Lewis RJ, Kool J, et al. Multifunctional toxins in snake venoms and therapeutic implications: from pain to hemorrhage and necrosis. Front Ecol Evol. 2019;7:218. doi: https://doi.org/10.3389/fevo.2019.00218
4. Kang TS, Georgieva D, Genov N, Murakami MT, Sinha M, Kumar RP, et al. Enzymatic toxins from snake venom: structural characterization and mechanism of catalysis. FEBS J. 2011;278(23):4544–76. doi: https://doi.org/10.1111/j.1742-4658.2011.08115.x
5. Gutiérrez JM, Calvete JJ, Habib AG, Harrison RA, Williams DJ, Warrell DA. Snakebite envenoming. Nat Rev Dis Primers. 2017;3:17063. doi: https://doi.org/10.1038/nrdp.2017.63
6. Alvarez-Flores MP, Faria F, de Andrade SA, Chudzinski-Tavassi AM. Snake venom components affecting the coagulation system. In: Gopalakrishnakone P, Inagaki H, Mukherjee A, Rahmy T, Vogel CW, editors. Snake venoms. Toxinology. Dordrecht, The Netherlands: Springer; 2016. doi: https://doi.org/10.1007/978-94-007-6648-8_31- 1(2016)
7. Di Nicola MR, Pontara A, Kass GEN, Kramer NI, Avella I, Pampena R, et al. Vipers of major clinical relevance in Europe: taxonomy, venom composition, toxicology and clinical management of human bites. Toxicology. 2021;453:152724. doi: https://doi.org/10.1016/j.tox.2021.152724
8. Bocian A, Urbanik M, Hus K, ?yskowski A, Petrilla V, Andrej?áková Z, et al. Proteome and peptidome of Vipera berus berus venom. Molecules. 2016;21(10):1398. doi: https://doi.org/10.3390/molecules21101398
9. Serrano SM, Shannon JD, Wang D, Camargo AC, Fox JW. A multifaceted analysis of viperid snake venoms by two-dimensional gel electrophoresis: an approach to understanding venom proteomics. Proteomics. 2005;5(2):501–10. doi: https://doi.org/10.1002/pmic.200400931
10. Munawar A, Trusch M, Georgieva D, Spencer P, Frochaux V, Harder S, et al. Venom peptide analysis of Vipera ammodytes meridionalis (Viperinae) and Bothrops jararacussu (Crotalinae) demonstrates subfamily-specificity of the peptidome in the family Viperidae. Mol Biosyst. 2011;7(12):3298–307. doi: https://doi.org/10.1039/c1mb05309d
11. Palamarchuk M, Niyazmetov T, Halenova T, Raksha N, Maievskyi O, Dzevulska I, et al. Effect of Vipera berus berus and Vipera berus nikolskii Venom on proteolytic balance in the tissue of the adrenal glands and testicles of rats. Biomed Biotechnol Res J. 2022;6(4):543– 9. doi: https://doi.org/10.4103/bbrj.bbrj_287_22
12. Rachkovska A, Krenytska D, Karbovskyy V, Halenova T, Raksha N, Vovk T, et al. Characteristics of products of fibrinogen origin in the presence of anti- SARS-CoV-2 IgG in the bloodstream. Rev Recent Clin Trials. 2023;18(1):69–75. doi: https://doi.org/10.2174/1574887118666221219115856
13. Matkivska R, Shchypanskyi S, Raksha N, Vovk T, Halenova T, Maievskyi O, et al. Venom-induced consumption coagulopathy in rats following Leiurus macroctenus (Scorpiones: Buthidae) envenomation. Curr Top Pept Protein Res. 2023;24:57064.
14. Rachkovska A, Krenytska D, Karbovskyy V, Raksha N, Halenova T, Vovk T, et al. A study of fibrinolytic system components in donor groups depending on various titers of circulating anti-SARS-CoV-2 IgG in the bloodstream. Blood Coagul Fibrin. 2023;34(7):439–45. doi: https://doi.org/10.1097/MBC.0000000000001248
15. Strubchevska K, Rachkovska A, Krenytska D, Karbovskyy V, Kozyk M, Secor B, et al. Coagulation parameters in post-covid-19 condition in relation to various titers of anti-SARS-CoV-2 IgG in blood plasma. Int J Gen Med. 2023;16:6127–35. doi: https://doi.org/10.2147/IJGM.S425496
16. Mackie I, Casini A, Pieters M, Pruthi R, Reilly-Stitt C, Suzuki A. International council forstandardisation in haematology recommendations onfibrinogen assays, thrombin clotting time and related tests inthe investigation of bleeding disorders. Int J Lab Hematol. 2024;46(1):20–32. doi: https://doi.org/10.1111/ijlh.14201
17. Dang XT, Xuan Nguyen T, Nguyen TTH, Ha HT. Coagulopathy after Viper Snakebite in Vietnam and relationship with time of admission. J Multidiscip Healthc. 2021;14:1259–65. doi: https://doi.org/10.2147/JMDH.S311556
18. Isbister GK, Maduwage K, Scorgie FE, Shahmy S, Mohamed F, Abeysinghe C, et al. Venom concentrations and clotting factor levels in a prospective cohort of Russell’s Viper bites with coagulopathy. PLoS Negl Trop Dis. 2015;9(8):e0003968. doi: https://doi.org/10.1371/journal.pntd.0003968
19. Storozhuk OB, Shevchuk SV, Storozhuk LO, Dovgalyuk TV, Storozhuk BG. Relationship between pre- and post-thrombosis factors in patients with stage VD CKD treated by long-term hemodialysis. Wiadomo?ci Lekarskie.2021;74(3):471–4.
20. Dineshkumar T, Dhanapriya J, Sakthirajan R, Thirumalvalavan K, Kurien AA, Balasubramaniyan T, et al. Thrombotic microangiopathy due to Viperidae bite: two case reports. Indian J Nephrol. 2017;27(2):161–4. doi: https://doi.org/10.4103/0971-4065.196936
21. Noutsos T, Currie BJ, Isbister GK. Snakebite associated thrombotic microangiopathy: a protocol for the systematic review of clinical features, outcomes, and role of interventions. Syst Rev. 2019;8:212. doi: https://doi.org/10.1186/s13643-019-1133-2
22. Kini RM. Anticoagulant proteins from snake venoms: structure, function and mechanism. Biochem J. 2006;397(3):377–87. doi: https://doi.org/10.1042/BJ20060302
23. Hutton RA, Warrell DA. Action of snake venom components on the haemostatic system. Blood Rev. 1993;7:176–89.
24. Rijken DC, Lijnen HR. New insights into the molecular mechanisms of the fibrinolytic system. J Thromb Haemost. 2009;7(1):4–13. doi: https://doi.org/10.1111/j.1538-7836.2008.03220.x
25. Sanchez EF, Flores-Ortiz RJ, Alvarenga VG, Eble JA. Direct fibrinolytic snake venom metalloproteinases affecting hemostasis: structural, biochemical features and therapeutic potential. Toxins (Basel). 2017;9(12):392. doi: https://doi.org/10.3390/toxins9120392
26. Kini RM, Koh CY. Metalloproteases affecting blood coagulation, fibrinolysis and platelet aggregation from snake venoms: definition and nomenclature of interaction Sites. Toxins. 2016;8(10):284. doi: https://doi.org/10.3390/toxins8100284
27. Calderón L, Lomonte B, Gutiérrez JM, Tarkowski A, Hanson LA. Biological and biochemical activities of Vipera berus (European viper) venom. Toxicon. 1993;31(6):743–53. doi: https://doi.org/10.1016/0041-0101(93)90380-2
28. Czajka U, Wiatrzyk A, Luty?ska A. Mechanism of Vipera berus venom activity and the principles of antivenom administration in treatment. Przegl Epidemiol. 2013;67(4):641–6.
29. Shitikov V, Malenyov A, Gorelov R, Bakiev A. “Dose-response” models with mixed parameters by the example of venom toxicity estimation of the common European adder Vipera berus // Principy èkologii. 2018;7(2):150160. doi: https://doi.org/10.15393/j1.art.2018.7542
30. Palamarchuk M, Bobr A, Mudrak A, Gunas I, Maievskyi O, Samborska I, et al. Proteolytic homeostasis in the tissue of the spleen and the heart of rats injected with the venom of Vipera berus berus and Vipera berus nikolskii. Curr Appl Sci Technol. 2023;23(6):19. doi: https://doi.org/10.55003/cast.2023.06.23.015
31. Raksha N, Vovk T, Halenova T, Mudrak A, Slyeptsova I, Mudrak H, et al. Influence of Vipera berus berus and Vipera berus nikolskii venom on protein-peptide profile in the liver, kidneys, and small intestine of rats. Curr Top Peptide Protein Res. 2022;23:63–72.
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