Reducing of the respiratory effects of dizocilpine by recombinant interleukin-1β in experiment

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Abstract

BACKGROUND: For a deeper understanding of the pathogenesis of COVID-19, it is necessary to study the mechanisms that implement the influence of pro-inflammatory cytokines on the processes of regulation of the external respiratory system. In experiments on anesthetized rats, the effect of the pro-inflammatory cytokine interleukin-1β on the respiratory effects of dizocilpine (MK-801), which has an inhibitory effect on neurotransmitter systems involved in the control of the respiratory system, was studied. It was considered that, first of all, dizocilpine is a highly effective non-competitive NMDA-type glutamate receptor blocker.

AIM: The objectives of the study were to identify the effect of the influence of dizocilpine on the parameters of the breathing pattern and to assess the degree of change in this effect when dizocilpine was administered against the background of an elevated systemic level of interleukin-1β.

MATERIALS AND METHODS: The study was performed on 24 anesthetized tracheostomy spontaneously breathing rats. To register the volume-time parameters of external respiration, a pneumotachographic technique was used. In the process of processing the obtained results, the value of the recorded parameter was determined immediately before the introduction of MK-801 and 1 min after its introduction

RESULTS: At a dosage of 0.1 mg/kg, dizocilpine was found to cause a reversible short-term decrease in respiratory rate, tidal volume, and minute respiratory volume. It has been shown that this effect of dizocilpine does not appear after intravenous administration of interleukin-1β (at a dosage of 2 μg/kg). The results obtained confirm the assumption about the effect of an elevated systemic level of interleukin-1β on the state of neurotransmitter systems involved in the control of respiration.

CONCLUSIONS: Based on the correlation of the obtained results with the literature data, an assumption was made about a change in the state of NMDA-type glutamate receptors under the influence of pro-inflammatory cytokines, which may be one of the mechanisms of cardiorespiratory dysfunctions observed in a systemic inflammatory reaction accompanied by hypercytokinemia.

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About the authors

Tatiana S. Tumanova

Pavlov Institute of Physiology of the Rusian Academy of Sciences; Herzen Russian State Pedagogical University

Email: tumanovats@infran.ru
ORCID iD: 0000-0001-6393-6699
SPIN-code: 9054-0304
Scopus Author ID: 57109162900

Junior Research Associate; Аssistant Lecturer

Russian Federation, Saint Petersburg; Saint Petersburg

Vladimir A. Merkurjev

Russian State University of Physical Culture, Sports, Youth and Tourism

Email: vladfiziologi@mail.ru
ORCID iD: 0000-0002-5399-5721
SPIN-code: 8386-8658

Cand. Sci. (Biol.), Senior Lecturer

Russian Federation, Moscow

Galina A. Danilova

Pavlov Institute of Physiology of the Rusian Academy of Sciences

Author for correspondence.
Email: danilovaga@infran.ru
ORCID iD: 0000-0001-8091-0618
SPIN-code: 6784-1326

Cand. Sci. (Biol.), Research Associate

Russian Federation, Saint Petersburg

Viacheslav G. Aleksandrov

Pavlov Institute of Physiology of the Rusian Academy of Sciences

Email: aleksandrovv@infran.ru
ORCID iD: 0000-0002-5079-633X
SPIN-code: 6752-2718
Scopus Author ID: 7202754123
ResearcherId: J-5698-2018

Dr. Sci. (Biol.), Professor, Leading Research Associate, Team Leader

Russian Federation, Saint Petersburg

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2. Figure. Weakening of the respiratory effects of dizocilpine (MK-801) when administered against the background of an elevated systemic level of IL-1β (n = 8): change in the frequency of respiratory movements (a), tidal volume (b), minute respiratory volume (c). The abscissa shows the time of action of IL-1β. The arrow indicates the moment of introduction of IL-1β. On the y-axis, the value of the parameter after the introduction of MK-801, expressed as a percentage. The value of the parameter immediately before the introduction of MK-801 was taken as 100%. * Significant changes in the parameter compared with the background, p < 0.05; # significant decrease in the value of the parameter 1 min after the introduction of MK-801

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