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Prophylactic and Therapeutic Administration of Leutragin Increases the Survival Rate of Animals in a Model of Fatal Acute Respiratory Distress Syndrome

https://doi.org/10.33647/2074-5982-16-4-44-51

Abstract

This study aims to investigate effects of leutragin, an opioid peptide analogue of endogenous dynorphin 1-6, on animal survival in an experimental model of “cytokine storm” and fatal acute respiratory distress syndrome (ARDS) in C57Bl/6Y mice under different administration regimens. The aforementioned factors cause a severe course of COVID-19, which explains the current interest in seeking new treatments for ARDS. It was shown that both the prophylactic (before ARDS induction) and therapeutic (after ARDS induction) administration of leutragin in a combined mode — intramuscular injection plus inhalation leads to a statistically significant increase in the survival rate of animals. Compared to the control, leutragin significantly reduced the risk of death in animals with ARDS. The discovered prophylactic effect of leutragin deserves special attention due to its potential in preventing the onset of the disease and impeding the development of severe lung damage, thus reducing the risk of ARDS and fatal outcomes. Thus, the use of leutragin can be seen as a new effective approach to the treatment and prevention of respiratory diseases associated with a “cytokine storm” and ARDS, including the coronavirus infection COVID-19.

About the Authors

V. N. Karkischenko
Scientific Center of Biomedical Technologies of the Federal Medical and Biological Agency of Russia
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

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

Melik T. Gasanov, Cand. Sci. (Med.), Assoc. Prof.

143442, Moscow region, Krasnogorsk district, Svetlye gory village, building 1



M. S. Nesterov
Scientific Center of Biomedical Technologies of the Federal Medical and Biological Agency of Russia
Russian Federation

Maxim S. Nesterov

143442, Moscow region, Krasnogorsk district, Svetlye gory village, building 1



Yu. V. Fokin
Scientific Center of Biomedical Technologies of the Federal Medical and Biological Agency of Russia
Russian Federation

Yuriy V. Fokin, Cand. Sci. (Biol.)

143442, Moscow region, Krasnogorsk district, Svetlye gory village, building 1



L. A. Taboyakova
Scientific Center of Biomedical Technologies of the Federal Medical and Biological Agency of Russia
Russian Federation

Lidiya A. Taboyakova

143442, Moscow region, Krasnogorsk district, Svetlye gory village, building 1



O. V. Alimkina
Scientific Center of Biomedical Technologies of the Federal Medical and Biological Agency of Russia
Russian Federation

Oksana V. Alimkina

143442, Moscow region, Krasnogorsk district, Svetlye gory village, building 1



D. V. Khvostov
Scientific Center of Biomedical Technologies of the Federal Medical and Biological Agency of Russia
Russian Federation

Daniil V. Khvostov

143442, Moscow region, Krasnogorsk district, Svetlye gory village, building 1



References

1. 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).

2. Karkischenko N.N. Osnovy biomodelirovaniya [Basics of biomodeling]. Moscow: Mezhakademicheskoye Izdatel’stvo VPK, 2004. 607 p. (In Russian).

3. 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).

4. Aoyagi T., Yamamoto N., Hatta M., Tanno D., Miyazato A., Ishii K., et al. Activation of pulmonary invariant NKT cells leads to exacerbation of acute lung injury caused by LPS through local production of IFN-γ and TNF-α by Gr-1+ monocytes. Int. Immunol. 2011;23(2):97–108.

5. Corbett A.D., Paterson S.J., McKnight A.T., Magnan J., Kosterlitz H.W. Dynorphin and dynorphin are ligands for the kappa-subtype of opiate receptor. Nature. 1982;299(5878):79–81. DOI: 10.1038/299079a0.

6. Crosby C.M., Kronenberg M. Tissue-specific functions of invariant natural killer T cells. Nat. Rev. Immunol. 2018;18(9):559–574.

7. D’Alessio F.R. Mouse Models of Acute Lung Injury and ARDS. Methods Mol. Biol. 2018;1809:341–350.

8. Fazalul Rahiman S.S., Morgan M., Gray P., Shaw P.N., Cabot P.J. Dynorphin 1-17 and Its N-Terminal Biotransformation Fragments Modulate Lipopolysaccharide-Stimulated Nuclear Factor-kappa B Nuclear Translocation, Interleukin-1beta and Tumor Necrosis Factor-alpha in Differentiated THP-1 Cells. PLoS One. 2016;11(4):e0153005. DOI: 10.1371/journal.pone.0153005.

9. Gubernatorova E.O., Gorshkova E.A., Polinova A.I., Drutskaya M.S. IL-6: Relevance for immunopathology of SARS-CoV-2. Cytokine Growth Factor Rev. 2020;53:13–24.

10. Henry B.M., de Oliveira M.H.S., Benoit S., Plebani M., Lippi G. Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): a meta-analysis. Clin. Chem. Lab. Med. 2020;58(7):1021–1028.

11. Kudo D., Toyama M., Aoyagi T., Akahori Y., Yamamoto H., Ishii K., et al. Involvement of high mobility group box 1 and the therapeutic effect of recombinant thrombomodulin in a mouse model of severe acute respiratory distress syndrome. Clin. Exp. Immunol. 2013;173(2):276–287.

12. Mitchell S., Vargas J., Hoffmann A. Signaling via the NFκB system. Wiley Interdiscip. Rev. Syst. Biol. Med. 2016;8(3):227–241. DOI: 10.1002/wsbm.1331.

13. Ogawa C., Liu Y.J., Kobayashi K.S. Muramyl dipeptide and its derivatives: peptide adjuvant in immunological disorders and cancer therapy. Curr. Bioact. Compd. 2011;7(3):180–197.

14. Yarygin K.N. The interactions of opioids with enterocytes membranes: evidence for enzyme-catalysed covalent binding. Collect. Czech. Chem. Commun. 1990;55:2328–2338.


Review

For citations:


Karkischenko V.N., Pomytkin I.A., Gasanov M.T., Nesterov M.S., Fokin Yu.V., Taboyakova L.A., Alimkina O.V., Khvostov D.V. Prophylactic and Therapeutic Administration of Leutragin Increases the Survival Rate of Animals in a Model of Fatal Acute Respiratory Distress Syndrome. Journal Biomed. 2020;16(4):44-51. (In Russ.) https://doi.org/10.33647/2074-5982-16-4-44-51

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ISSN 2074-5982 (Print)
ISSN 2713-0428 (Online)