The Combined Use of Leutragin and Pulmonary Surfactant-BL Increases Animal Survival in a Model of Fatal Acute Respiratory Distress Syndrome
https://doi.org/10.33647/2074-5982-16-4-52-59
Abstract
This study aims to investigate effects of leutragin — a stabilized analogue of the endogenous hexapeptide dynorphin 1-6 — in combination with pulmonary surfactant-BL on animal survival in an experimental fatal model of “cytokine storm” and acute respiratory distress syndrome (ARDS) in C57Bl/6Y mice. Compared to the control, administration of leutragin and pulmonary surfactant-BL in a combined regimen led to a statistically significant increase in the survival rate and a decrease in the risk of death in animals with ARDS. It was shown that the suppression of proinflammatory cytokine production in the lungs with a simultaneous replenishment of the endogenous surfactant with an exogenous pulmonary surfactant is a promising new pharmacological approach to the treatment of ARDS accompanied by a “cytokine storm”.
About the Authors
V. N. Karkischenko
Scientific Center of Biomedical Technologies of the Federal Medical and Biological Agency of Russia
Russian Federation
Russian Federation
Vladislav N. Karkischenko, Dr. Sci. (Med.), Prof.
143442, Moscow region, Krasnogorsk district, Svetlye gory village, building 1
I. A. Pomytkin
Scientific Center of Biomedical Technologies of the Federal Medical and Biological Agency of Russia
Russian Federation
Russian Federation
Igor A. Pomytkin, Cand. Sci. (Chem.)
143442, Moscow region, Krasnogorsk district, Svetlye gory village, building 1
M. T. Gasanov
Scientific Center of Biomedical Technologies of the Federal Medical and Biological Agency of Russia
Russian Federation
Russian Federation
Melik T. Gasanov, Cand. Sci. (Med.), Assoc. Prof.
143442, Moscow region, Krasnogorsk district, Svetlye gory village, building 1
O. I. Stepanova
Scientific Center of Biomedical Technologies of the Federal Medical and Biological Agency of Russia
Russian Federation
Russian Federation
Olga I. Stepanova, Cand. Sci. (Biol.)
143442, Moscow region, Krasnogorsk district, Svetlye gory village, building 1
R. A. Klesov
Scientific Center of Biomedical Technologies of the Federal Medical and Biological Agency of Russia
Russian Federation
Russian Federation
Roman A. Klesov
143442, Moscow region, Krasnogorsk district, Svetlye gory village, building 1
N. S. Ogneva
Scientific Center of Biomedical Technologies of the Federal Medical and Biological Agency of Russia
Russian Federation
Russian Federation
Nastasya S. Ogneva
143442, Moscow region, Krasnogorsk district, Svetlye gory village, building 1
E. S. Savchenko
Scientific Center of Biomedical Technologies of the Federal Medical and Biological Agency of Russia
Russian Federation
Russian Federation
Elena S. Savchenko
143442, Moscow region, Krasnogorsk district, Svetlye gory village, building 1
V. I. Skvortsova
Federal Medical and Biological Agency of Russia
Russian Federation
Russian Federation
Veronika I. Skvortsova, Dr. Sci. (Med.), Prof., Corresponding Member of the Russian Academy of Sciences
123182, Moscow, Volokolamskoye highway, 30
References
1. Bautin A.E., Osovskih V.V., Hubulava G.G., Granov D.A., Kozlov I.A., Erohin V.V., et al. Mnogocentrovye klinicheskie ispytaniya surfaktantaBL dlya lecheniya respiratornogo distress-sindroma vzroslyh [Multicenter clinical trials of surfactant BL for the treatment of adult respiratory distress syndrome]. Klinicheskie issledovaniya lekarstvennyh sredstv v Rossii [Clinical Trials of Medicines in Russia]. 2002;2:18–23. (In Russian).
2. Diagnostika i intensivnaya terapiya ostrogo respiratornogo distress-sindroma [Diagnostics and intensive care of acute respiratory distress syndrome]: Clinical guidelines. Federation of Anesthesiologists and Resuscitators. Ministry of Health Care of the Russian Federation. Approved March 30, 2020. (In Russian).
3. Karkischenko N.N. Al’ternativy biomediciny. T. 1. Osnovy biomediciny i farmakomodelirovaniya [Biomedicine alternatives. Vol. 1. Fundamentals of biomedicine and pharmaco-modeling]. Moscow: Izdatel’stvo VPK, 2007. 320 p. (In Russian).
4. Karkischenko N.N. Osnovy biomodelirovaniya [Basics of biomodeling]. Moscow: Mezhakademicheskoye Izdatel’stvo VPK, 2004. 607 p. (In Russian).
5. Rozenberg O.A. Preparaty legochnogo surfaktanta i surfaktantterapiya ORDS v usloviyah hirurgicheskoj reanimacii (obzor lit-ry) [Pulmonary surfactant preparations and surfactant therapy for ARDS in surgical resuscitation (literature review)]. Kreativnaya hirurgiya i onkologiya [Creative Surgery and Oncology]. 2019;9(1):50–65. (In Russian).
6. Rukovodstvo po laboratornym zhivotnym i al’ternativnym modelyam v biomedicinskih issledovaniyah [Manual on laboratory animals and alternative models in biomedical research]. Ed. by N.N. Karkischenko, et al. Moscow: Profil’-2S Publ., 2010. 358 p. (In Russian).
7. Bank U., Reinhold D., Kunz D., Schulz H.U., Schneemilch C., Brandt W., et al. Effects of interleukin-6 (IL-6) and transforming growth factorbeta (TGF-beta) on neutrophil elastase release. Inflammation. 1995;19(1):83–99.
8. Bellani G., Laffey J.G., Pham T., et al. Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries. JAMA. 2016;315:788–800.
9. Creuwels L.A., van Golde L.M., Haagsman H.P. The pulmonary surfactant system: biochemical and clinical aspects. Lung. 1997;175(1):1–39.
10. Eworuke E., Major J.M., Gilbert McClain L.I. National incidence rates for Acute Respiratory Distress Syndrome (ARDS) and ARDS cause-specific factors in the United States (2006–2014). J. Crit. Care. 2018;47:192–197.
11. Hirche T.O., Crouch E.C., Espinola M., Brokelman T.J., Mecham R.P., DeSilva N., et al. Neutrophil serine proteinases inactivate surfactant protein D by cleaving within a conserved subregion of the carbohy-drate recognition domain. J. Biol. Chem. 2004;279(26):2768827698.
12. Pison U., Tam E.K., Caughey G.H., Hawgood S. Proteolytic inactivation of dog lung surfactantassociated proteins by neutrophil elastasa. Biochim. Biophys. Acta. 1989;992(3):251–257.
13. Potey P.M., Rossi A.G., Lucas C.D., Dorward D.A. Neutrophils in the initiation and resolution of acute pulmonary inflammation: understanding biological function and therapeutic potential. J. Pathol. 2019;247(5):672–685.
14. Ranieri V.M., Rubenfeld G.D., Thompson B.T., et al. ARDS Definition Task Force. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012;307(23):2526–2533.
15. Rosenberg O.A., Bautin A.E., Osovskich V.V., Tsibulkin E.K., Gavrilin S.V., Kozlov I.A., et al. When to start surfactant therapy (STtherapy) of acute lung injury? Eur. Respir. J. 2001;18(38):153.
16. Rubio F., Cooley J., Accurso F.J., Remold O’Donnell E. Linkage of neutrophil serine proteases and decreased surfactant protein-A (SP-A) levels in inflammatory lung disease. Thorax. 2004;59(4):318–323.
17. Tzotzos S.J., Fischer B., Fischer H., Zeitlinger M. Incidence of ARDS and outcomes in hospitalized patients with COVID-19: a global literature survey. Crit. Care. 2020;24(1):516.
Review
For citations:
Karkischenko V.N., Pomytkin I.A., Gasanov M.T., Stepanova O.I., Klesov R.A., Ogneva N.S., Savchenko E.S., Skvortsova V.I. The Combined Use of Leutragin and Pulmonary Surfactant-BL Increases Animal Survival in a Model of Fatal Acute Respiratory Distress Syndrome. Journal Biomed. 2020;16(4):52-59. (In Russ.) https://doi.org/10.33647/2074-5982-16-4-52-59
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