pmedpharmФармация и фармакологияPharmacy & Pharmacology2307-92662413-2241Pyatigorsk Medical and Pharmaceutical Institute - branch of Volgograd State Medical Univer10.19163/2307-9266-2020-8-3-181-194pmedpharm-712Research ArticleФАРМАКОЛОГИЯ И КЛИНИЧЕСКАЯ ФАРМАКОЛОГИЯPHARMACOLOGY AND CLINICAL PHARMACOLOGYАНТИБАКТЕРИАЛЬНЫЕ И ИММУНОТРОПНЫЕ СВОЙСТВА ИЗОЛИКВИРИТИГЕНИНА ПРИ ГЕНЕРАЛИЗОВАННОЙ СТАФИЛОКОККОВОЙ ИНФЕКЦИИ У МЫШЕЙANTIBACTERIAL AND IMMUNOTROPIC PROPERTIES OF ISOLIQUIRITIGENIN IN GENERALIZED STAPHYLOCOCCAL INFECTION IN MICEhttps://orcid.org/0000-0001-6104-0864СолёноваЕ. А.SolyonovaE. A.

Солёнова Елена Александровна – младший научный сотрудник кафедры фармакологии, клинической фармакологии и биохимии 

428015, Чувашская Республика, г. Чебоксары, пр. Московский, д. 15

Elena A. Solyonova – Junior Researcher, Department of Pharmacology, Clinical Pharmacology and Biochemistry 

15, Moskovsky prospect, Cheboksary, Chuvash Republic, 428015

elensoul@mail.ruhttps://orcid.org/0000-0001-9976-7866ПавловаС. И.PavlovaS. I.

Павлова Светлана Ивановна – доктор медицинских наук, заведующая кафедрой фармакологии, клинической фармакологии и биохимии 

428015, Чувашская Республика, г. Чебоксары, пр. Московский, д. 15

Svetlana I. Pavlova – Doctor of Sciences (Medicine), the Head of the Department of Pharmacology, Clinical Pharmacology and Biochemistry 

15, Moskovsky prospect, Cheboksary, Chuvash Republic, 428015

flavonoid@yandex.ruФедеральное государственное бюджетное образовательное учреждение высшего образования «Чувашский государственный университет им. И.Н. Ульянова»РоссияChuvash State University named after I.N. UlyanovRussian Federation20202112202083181194Copyright © Солёнова Е.А., Павлова С.И., 20202020Солёнова Е.А., Павлова С.И.Solyonova E.A., Pavlova S.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.pharmpharm.ru/jour/article/view/712

Статья посвящена изучению эффектов изоликвиритигенина при генерализованной бактериальной инфекции.

Цель

Цель: изучение антибактериальных и иммунотропных механизмов и эффектов изоликвиритигенина при генерализованной стафилококковой инфекции в мышиной модели.

Материалы и методы

Материалы и методы. Для оценки выживаемости мышей линии Balb/C использовали модель генерализованной инфекции, вызванной Staphylococcus aureus J49 ATCC 25923 с построением кривых Каплан-Мейера. Степень бактериемии при развитии инфекции определяли методом секторных посевов. Минимальную подавляющую концентрацию изоликвиритигенина в отношении Staphylococcus aureus J49 ATCC 25923 определяли методом серийных разведений. Для исследования антибиопленочной активности использовали МТТ-тест и атомно-силовую микроскопию. Иммунотропные эффекты изучали, оценивая пептон-индуцированную миграцию фагоцитов в брюшную полость, пролиферацию митоген-активированных лимфоцитов в МТТ-тесте и секрецию ими цитокинов с помощью набора MILLIPLEX MAP на мультиплексном анализаторе Magpix.

Результаты

Результаты. Установлено, что предварительное внутрибрюшинное введение изоликвиритигенина (30 мг/кг) увеличивает выживаемость мышей Balb/C при генерализованной стафилококковой инфекции. Изоликвиритигенин обладает антибактериальной (MПК = 64 мкг/мл) и антибиопленочной (4–32 мкг/мл) активностью в отношении S. aureus J49 ATCC 25923, не ингибирует миграцию фагоцитов брюшную полость, дозозависимо подавляет пролиферацию и секрецию цитокинов митоген-активированными Т-лимфоцитами и модулирует выработку цитокинов (IL-2, IL-12p70, IFNg, TNFα, IL-6, IL-22, IL-23, IL-17A, IL-17F, IL-17E/IL-25, GM-CSF, MIP-3a/CCL20, IL-10) клетками паховых лимфатических узлов и спленоцитов на ранних стадиях генерализованной стафилококковой инфекции.

Заключение

Заключение. Предварительное введение изоликвиритигенина повышает выживаемость мышей при генерализованной стафилококковой инфекции, что может быть связано как с антимикробными (антистафилококковым, антибиопленочным действием), так и иммунотропными механизмами. Полученные данные о фармакодинамике изоликвиритигенина заслуживают внимания с точки зрения перспективы создания новых лекарственных препаратов, снижающих летальность при стафилококковом сепсисе.

The article is devoted to the study of the effects of isoliquiritigenin in generalized bacterial infections.

The aim is to study antibacterial and immunotropic mechanisms and effects of isoliquiritigenin in generalized staphylococcal infections in a mouse model.

Materials and methods

Materials and methods. To assess the survival rate of Balb/C mice, a generalized infection model caused by Staphylococcus aureus J49 ATCC 25923 with Kaplan-Meier curves was used. The degree of bacteremia during the development of infection was determined by the method of sector crops. The minimum inhibitory concentration of isoliquiritigenin against Staphylococcus aureus J49 ATCC 25923 was determined by serial dilutions methods. To study an antibiofilm activity, the MTT test and atomic force microscopy were used. Immunotropic effects were studied by assessing peptone-induced migration of phagocytes into the abdominal cavity, proliferation of mitogen-activated lymphocytes in the MTT test and their cytokine secretion using the MILLIPLEX MAP kit on a Magpix multiplex analyzer.

Results

Results. It has been established that a preliminary intraperitoneal administration of isoliquiritigenin (30 mg/kg) increases the survival rate of Balb/C mice in case of generalized staphylococcal infections. Isoliquiritigenin has antibacterial (MOC = 64 μg/ml) and antibiofilm (4–32 μg/ml) activities against S. aureus J49 ATCC 25923, does not inhibit the migration of phagocytes in the abdominal cavity, dose-dependently inhibits the proliferation and secretion of cytokines by mitogenactivated T-lymphocytes and modulates the production of cytokines (IL-2, IL-12p70, IFNg, TNFα, IL-6, IL-22, IL-23, IL-17A, IL-17F, IL-17E/IL-25, GM-CSF, MIP – 3a/CCL20, IL-10) by the cells of inguinal lymph nodes and splenocytes in the early stages of generalized staphylococcal infections.

Conclusion

Conclusion. A preliminary administration of isoliquiritigenin increases the survival rate of mice with generalized staphylococcal infections, which may be associated with both antimicrobial (antistaphylococcal, antibiofilm) and immunotropic mechanisms. The obtained data on the pharmacodynamics of isoliquiritigenin deserve attention from the point of view of the prospects of the new drugs creation that reduce mortality in staphylococcal sepsis.

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The authors declare that there are no conflicts of interest present.