Anti-cytokine effects of chalcon analogues in experimental "cytokine storm" in rats

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Abstract

The aim of the study was to evaluate the anti-cytokine effects of chalcon analogues in an experimental “cytokine storm”.

Materials and methods. The “cytokine storm” was modeled in rats by intraperitoneal injection of lipopolysaccharide at a dose of 10 mg / kg. The test compounds and the reference drug dexamethasone were administered intraperitoneal 60 minutes after lipopolysaccharide injection at doses of 20 mg / kg and 3 mg / kg, respectively. After 24 hours, changes of the cytokines concentration in blood serum (IL-1â, IL-6, IL-10, and TNF-á), body temperature, and the severity of pulmonary edema were evaluated.

Results. In the study, it was found that the administration of all the test-compounds reduced symptoms of hypercytokinemia, reflected in the decrease in the concentration of proinflammatory cytokines IL-1â, IL-6, and TNF-á with high content of IL-10 in serum. At the same time, the body temperature and pulmonary edema in rats against the background of the injection of the test chalcon analogues relative to animals that did not receive pharmacological support also decreased. Against the background of the administration of dexamethasone to animals, the concentration of IL-6, IL-1â and TNF-á decreased by 25.0% (p < 0.05); 44.1% (p < 0.05) and 33.3% (p < 0.05), as well as an increase in the content of IL-10 by 60.0% (p < 0.05), with a decrease in pulmonary edema and body temperature. It should be noted that there were no statistically significant differences between the groups of animals that were received the studied chalcon analogues and the reference drug.

Conclusion. The study showed the relevance of further study of representatives of a number of chalcon derivatives as non-hormonal means of correcting the “cytokine storm” with a high therapeutic potential.

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About the authors

Maksim V. Chernikov

Pyatigorsk Medical-Pharmaceutical Institute — branch of Volgograd State Medical University

Email: pharmax@list.ru

MD, PhD, DSc (Medicine), Associate Professor, Chair of the Department of Pharmacology with a Course of Clinical Pharmacology

Russian Federation, Pyatigorsk

Dmitriy I. Pozdnyakov

Pyatigorsk Medical-Pharmaceutical Institute — branch of Volgograd State Medical University

Author for correspondence.
Email: pozdniackow.dmitry@yandex.ru

MD, PhD (Pharmacology), Associate Professor of the Department of Pharmacology with a Course of Clinical Pharmacology

Russian Federation, Pyatigorsk

Victoria M. Rukovitsina

Pyatigorsk Medical-Pharmaceutical Institute — branch of Volgograd State Medical University

Email: v.m.rucovitcina@mail.ru

Post-Graduate student of the Department of Organic Chemistry

Russian Federation, Pyatigorsk

Eduard T. Oganesyan

Pyatigorsk Medical-Pharmaceutical Institute — branch of Volgograd State Medical University

Email: edwardow@mail.ru

MD, PhD, DSc (Pharmaco­logy), Professor, Head of the Department of Organic Chemistry

Russian Federation, Pyatigorsk

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Supplementary files

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6. Fig. 1. Effect of the test-compounds and dexamethasone on changes in rat’s body temperature under experimental “cytokine storm” conditions. IN — intact animals; NC — Negative control group; # statistically significant relative to intact animals (Newman-Keuls test, p < 0.05); * statistically significant relative to the negative control group (Newman – Keuls test, p < 0.05)

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7. Fig. 2. The effect of the test-compounds and dexamethasone on the change in the severity of pulmonary edema in rats under the conditions of an experimental “сytokine storm”. IN — intact animals; NC — Negative control group; # statistically significant relative to intact animals (Newman – Keuls test, p < 0.05); * statistically significant relative to the negative control group (Newman – Keuls test, p < 0.05)

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Copyright (c) 2021 Chernikov M.V., Pozdnyakov D.I., Rukovitsina V.M., Oganesyan E.T.

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