A rationale for application of immobilized subtilisines for target therapy of venous thrombosis
https://doi.org/10.31549/2542-1174-2020-1-76-88
Abstract
To determine the efficacy and safety of the drug based on immobilized subtilisin (SUBT), we conducted experimental (using Wistar and Balb/C male rats) and clinical (VETTER-1 — Venous Thrombosis Therapy) studies. Experimental studies have shown the direct thrombolytic effect of SUBT on 1-, 2- and 24-hour blood clots (in vitro) and the absence of local changes in rats with κ-carrageenan-induced thrombosis (in vivo). In a clinical study, patients receiving SUBT showed an increase in blood flow by 5% from the initial, or recanalization of a vein which was observed 1.5–1.6 times more often than in patients receiving placebo.
Thus, a drug based on SUBT can be used in the treatment of venous thrombosis.
About the Authors
S. V. Mishenina
Novosibirsk State Medical University
Russian Federation
Russian Federation
Mishenina Svetlana Vladimirovna — Associate Professor, Department of Pharmacology, Clinical Pharmacology and Evidence-Based Medicine
52, Krasny Prospect, Novosibirsk, 630091
G. I. Baykalov
Novosibirsk State Medical University
Russian Federation
Baikalov German Igorevich — Graduate Student, Department of Pharmacology, Clinical Pharmacology and Evidence-Based Medicine
Russian Federation
Baikalov German Igorevich — Graduate Student, Department of Pharmacology, Clinical Pharmacology and Evidence-Based Medicine
N. E. Baikalova
Novosibirsk State Medical University
Russian Federation
Baikalova Natalya Evgenyevna — Resident, Department of Obstetrics and Gynecology
Russian Federation
Baikalova Natalya Evgenyevna — Resident, Department of Obstetrics and Gynecology
V. K. Makarov
Novosibirsk State Medical University
Russian Federation
Makarov Vyacheslav Konstantinovich — Student, Faculty of Dentistry
Russian Federation
Makarov Vyacheslav Konstantinovich — Student, Faculty of Dentistry
P. G. Madonov
Novosibirsk State Medical University
Russian Federation
Madonov Pavel Gennadyevich — Dr. Sci. (Med.), Professor, Head, Department of Pharmacology, Clinical Pharmacology and Evidence-Based Medicine
Russian Federation
Madonov Pavel Gennadyevich — Dr. Sci. (Med.), Professor, Head, Department of Pharmacology, Clinical Pharmacology and Evidence-Based Medicine
References
1. Hoffman M., Monroe D.M. (2001). A cell-based model of hemostasis. Thromb. Haemost., 85 (6), 958–965. doi: 10.1055/s-0037-1615947.
2. Lobastov K.V., Dementieva G.I., Laberko L.A. (2019). Current insights on the etiology and pathogenesis of venous thrombosis: Virchow’s triad revision. Journal of Venous Disorders, 13 (3), 227–235.
3. Schastlivtsev I.V., Lobastov K.V., Tsaplin S.N., Mkrtychev D.S. (2019). Modern view on hemostasis system: cell theory. Medical Council, 16, 72–77.
4. Zhitkova Yu.V., Aisina R.B., Varfolomeev S.D. (1996). Kinetics of fibrinolysis by plasmin: inhibition by the products of fibrin degradation. Bioorganic Chemistry, 22 (12), 911–915. In Russ.
5. Baldwin J.F., Sood V., Megan A. et al. (2012, Oct). The role of urokinase plasminogen activator and plasmin activator inhibitor-1 on vein wall remodeling in experimental deep vein thrombosis. Vasc. Surg., 56 (4), 1089–1097. doi: 10.1016/j.jvs.2012.02.054.
6. Wahlgren N., Ahmed N., Dávalos A. et al. (2007). Thrombolysis with alteplase for acute ischaemic stroke in the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST): an observational study. Lancet, 369 (9558), 275–282.
7. Donkel S.J., Benaddi B., Dippel D.W.J., Ten Cate H., de Maat M.P.M. (2019). Prognostic hemostasis biomarkers in acute ischemic stroke. Arterioscler. Thromb. Vasc. Biol., 39, 360–372.
8. Szegedi I., Nagy A., Szekely E.G. et al. (2019). PAI-1 5G/5G genotype is an independent risk of intracranial hemorrhage in post-lysis stroke patients. Ann. Clin. Transl. Neurol., 6 (11), 2240–2250. doi: 10.1002/acn3.50923.
9. Liu S.Q., Guo J.Y., Du J. et al. (2013, Jul-Aug). Anticoagulant effect of Huisheng Oral Solution in a rat model of thrombosis. Indian J. Pharmacol., 45 (4), 359–364. doi: 10.4103/0253-7613.115018.
10. Scheer F.A., Shea S.A. (2014). Human circadian system causes a morning peak in prothrombotic plasminogen activator inhibitor-1 (PAI-1) independent of the sleep/wake cycle. Blood, 123, 590–593.
11. Kim W., Choi K., Kim Y. et al. (1996). Purification and characterization of a fibrinolytic enzyme produced from Bacillus sp. strain CK 11-4 screened from chungkook-jang. Appl. Environ. Microbiol., 62 (7), 24822488.
12. Baskova I.P., Kalabushev S.N., Akhaev D.N. et al. (2018, May). Role of isopeptidolysis in the process of thrombolysis. Thromb. Res., 165, 18–23.
13. Avhad D.N., Vanjari S.S., Virendra K. (2013). A novel fibrinolytic enzyme from Bacillus sphaericus MTCC3672: optimization and purification studies. Am. J. Cur. Microbiol., 1, 1–13.
14. Peng Y., Huang Q., Zhang R.H., Zhang Y.Z. (2003). Purification and characterization of a fibrinolytic enzyme produced by Bacillus amyloliquefaciens DC-4 screened from douchi, a traditional Chinese soybean food. Comp. Biochem. Physiol. Pt. B: Biochem. Mol. Biol., 134 (1), 45–52.
15. Dygay A.M., Zyuz’Kov G.N., Zhdanov V.V. et al. (2012). Hypoglycemic effects of hyaluronate-endoβ-NAcetylhexosaminidase immobilized by electron beam synthesis nanotechnology. Bulletin of Experimental Biology and Medicine, 153 (1), 106–109.
16. Kinsht D.N., Madonov P.G., Lastovetskiy A.G., Kitanina K.Yu., Udut V.V. (2017). Technology of electron-beam synthesis as a perspective direction in development of immobilized interferons for oral use (literature report). Journal of New Medical Technologies, 3, 211–225.
17. Bekemeier H., Giessler A.J. (1987). Thrombosis induction by different carrageenans in rats and mice. Naturwissenschaften, 74, 345–346.
Review
For citations:
Mishenina S.V., Baykalov G.I., Baikalova N.E., Makarov V.K., Madonov P.G. A rationale for application of immobilized subtilisines for target therapy of venous thrombosis. Journal of Siberian Medical Sciences. 2020;(1):76-88. https://doi.org/10.31549/2542-1174-2020-1-76-88
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