Исследование противовоспалительной, анальгезирующей, ульцерогенной и антиульцерогенной активности металлокомплекса цинка производного N-изопропенилимидазола

Авторы

DOI:

https://doi.org/10.18413/rrpharmacology.10.443

Аннотация

Введение. Несмотря на несомненную лечебную эффективность нестероидных противовоспалительных средств, они могут вызывать серьезные побочные эффекты, из которых одним из наиболее грозных является ульцерогенное действие, влекущее за собой снижение качества жизни, а иногда и смертельные исходы. Это диктует необходимость поиска и разработки новых молекул, обладающих высокой противовоспалительной активностью, не проявляющих гастротоксического действия. 

Цель работы – изучить противовоспалительную, анальгезирующую, ульцерогенную и антиульцерогенную активность металлокомплекса цинка производного N-изопропенилимидазола.

Материалы и методы. Определение средней летальной дозы – ЛД50 металлокомплекса цинка производного N-изопропенилимидазола (лабораторный шифр Пилим-1) проводили в опытах на крысах и мышах. Модели острого экссудативного и хронического пролиферативного воспаления создавали в первом случае путем субплантарного введения в заднюю лапу крыс каррагенина и полного адъюванта Фрейнда, а во втором – посредством имплантирования под кожу крыс стерильного ватного шарика («ватная гранулема»). Острую и тоническую, висцеральную и соматическую глубокую боль моделировали соответственно с помощью «формалинового теста» у крыс и теста «уксусные корчи» у мышей. Ульцерогенное и антиульцерогенное действие Пилима-1 исследовали в опытах на крысах. Пилим-1 и референс-препараты диклофенак, индометацин и фамотидин применяли внутрижелудочно.

 Результаты исследований и их обсуждение. Пилим-1 менее токсичен, чем диклофенак и индометацин, обладает выраженными противовоспалительным и анальгезирующим эффектами, при этом по активности близок к диклофенаку и превосходит индометацин. По широте терапевтического действия более значим, чем диклофенак и индометацин, в отличие от последних практически не оказывает ульцерогенного действия, проявляет более значимую антиульцерогенную активность, чем фамотидин. Важную роль в механизмах противовоспалительного, анальгезирующего и гастропротекторного действия, по-видимому, играет способность Пилима-1 оказывать антигипоксическое и антиоксидантное действие, ингибирующее влияние на циклооксигеназу и 5-липооксигеназу, а также наличие в его структуре цинка и имидазола, обладающих широким спектром биологической активности.

Заключение. Сравнительно (по отношению к диклофенаку и индометацину) меньшая острая токсичность и выраженные противовоспалительный, анальгезирующий и антиульцерогенный эффекты, большая широта терапевтического действия, а также крайне низкая (практически отсутствующая) ульцерогенная активность Пилима-1 позволяют рекомендовать его для дальнейшего доклинического изучения.

Графическая аннотация

Ключевые слова:

анальгезирующая активность, антиульцерогенная активность, диклофенак, индометацин, металлокомплекс цинка производного N-изопропенилимидазола, острая токсичность, противовоспалительная активность, ульцерогенная активность

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Вклад авторов

Павел А. Галенко-Ярошевский, Кубанский государственный медицинский университет

Сorresponding member of the Russian Academy of Sciences, Holder of Advanced Doctorate (Doctor Habil. of Science) in Medical Sciences, Professor, Head of the Department of Pharmacology of Kuban State Medical University, Krasnodar, Russia; е-mail: Galenko.Yaroсhevsky@gmail.com; ORCID ID https://orcid.org/0000-0003-3190-1437. The author’s contribution: concept development–conceptualization and direction development of the research; methodology development and design; generation of key aims and objectives.

Ольга В. Шелемех, Ростовский государственный медицинский университет

Postgraduate student of the Department of Dentistry No.4 of Rostov State Medical University, Rostov-on-Don, Russia; e-mail: lioli777@yandex.ru; ORCID ID https://orcid.org/0000-0003-3488-9971. The author’s contribution: experimentation,data collection and analysis, statistical data processing and compilation of the manuscript.

Виктор Л. Попков, Кубанский государственный медицинский университет

Holder of Advanced Doctorate (Doctor Habil. of Science) in Medical Sciences, Professor of the Department of Orthopedic Dentistry of Kuban State Medical University, Krasnodar, Russia; e-mail: vict.popkoff2015@yandex.ru; ORCID ID https://orcid.org/0000-0001-7362-0073. The author’s contribution: defining the key aims and objectives, critical revision of the manuscript and its analysis, providing valuable comments.

Андрей В. Задорожний, Ростовский государственный медицинский университет

PhD in Medical Sciences, Associate Professor, Head of the Department of Dentistry No.4 of Rostov State Medical University, Rostov-on-Don, Russia;e-mail: stomvr1@gmail.com; ORCID IDhttps://orcid.org/0000-0001-9552-8542. Author's contribution: editing and preparation of the article text, participation in scientific design; resource support of the research–C&E materials, animals, instruments, computers for analysis; correction of the final version of the article

Ирина Б. Нектаревская, Ростовский государственный медицинский университет

PhD in Medical Sciences, Associate Professor of the Department of Dentistry No.4 of Rostov State Medical University, Rostov-on-Don, Russia; е-mail: nektir4546@mail.ru; ORCID ID https://orcid.org/0009-0009-6733-9977. Author's contribution: search for and analysis of information; animal keeping control, participation in the analysis of the research

Наталья Д. Бунатян, Первый Московский государственный медицинский университет имени И.М. Сеченова; Федеральное Государственное Бюджетное Учреждение «Научный центр экспертизы средств медицинского применения»

Holder of Advanced Doctorate (Doctor Habil. of Science) in Pharmaceutical Sciences, Professor, Head of the Department of Pharmaceutical Technology and Pharmacology of Institute of Professional Education of I.M. Sechenov First Moscow State Medical University, Moscow, Russia; Russia; Federal State Budgetary Institution "Scientific Centre for Expert Evaluation of Medicinal Products" of the Ministry of Health of the Russian Federation, Moscow, Russia; e-mail: ndbun@mail.ru; ORCID ID https://orcid.org/0000-0001-9466-1261. The author’s contribution: participation in preparing the final version of the manuscript in terms of visualization and data presentation.

Роман А. Мурашко, Кубанский государственный медицинский университет

Holder of Advanced Doctorate (Doctor Habil. of Science) in Medical Sciences, Associate Professor of the Department of Oncology withthe Course of Thoracic Surgery, Faculty of Advanced Trainingand Professional Retraining of Specialistsof Kuban State Medical University, Krasnodar, Russia; е-mail: ramurashko@rambler.ru; ORCID IDhttps://orcid.org/0000-0001-8873-8461. Author's contribution: defining the key aims and objectives, critical revision of the manuscript and providing valuable com

Светлана А. Лебедева, Первый Московский государственный медицинский университет имени И.М. Сеченова

Holder of Advanced Doctorate (Doctor Habil. of Science) in Biological Sciences, Professor of the Department of Pharmacology of Institute of Pharmacy named after A.P. Nelyubin of I.M. Sechenov First Moscow State Medical University, Moscow, Russia; e-mail: Lebedeva502@yandex.ru; ORCID ID https://orcid.org/0000-0001-8769-1040. The author’s contribution: defining the key aims and objectives; critical revision of the manuscript, providing valuable comments.

Анаит В. Зеленская, Кубанский государственный медицинский университет

PhD in Medical Sciences, Associate Professor of the Department of Pharmacology of Kuban State Medical University, Krasnodar, Russia; е-mail: anait_06@mail.ru; ORCID ID https://orcid.org/0000-0001-9512-2526. Author's contribution: analysis and interpretation of research results; preparation and editing of the article text; participation in scientific design.

Александр В. Уваров, Кубанский государственный медицинский университет

PhD in Medical Sciences, Associate Professor of the Department of Pharmacology of Kuban State Medical University, Krasnodar, Russia; e-mail: ytovkach@rambler.ru; ORCID ID https://orcid.org/0000-0003-0337-2689. Author's contribution: experimentation; analysis and interpretation of research results; participation in scienti

Ольга Н. Гулевская, Кубанский государственный университет физической культуры, спорта и туризма

PhD in Medical Sciences, Associate Professor of the Department of Adaptive Physical Culture of Kuban State University of Physical Culture, Sports and Tourism, Krasnodar, Russia; e-mail: olga.stoyalova@bk.ru, ORCID ID https://orcid.org/0000-0001-7205-2473. Author's contribution: experimentation; analysis and interpretation of research results; participation in scientific design.

Лусине О. Алуханян, Кубанский государственный медицинский университет

PhD in Medical Sciences, Associate Professor of the Department of Pediatric Dentistry, Orthodontics and Maxillofacial Surgery of Kuban State Medical University, Krasnodar, Russia; е-mail: lus.0912@mail.ru; ORCID ID https://orcid.org/0009-0005-1752-2491. Author's contribution: experimentation; analysis and interpretation of research results; participation in scientific design.

Тереза Р. Глечян, Кубанский государственный медицинский университет

Assistant Professor of the Department of Pharmacology of Kuban State Medical University, Krasnodar, Russia; e-mail: t_g91@mail.ru; ORCID ID https://orcid.org/0009-0002-4983-2433. Author's contribution: experimentation; analysis and interpretation of research results; participation in scientific design.

Алина В. Сергеева, Кубанский государственный медицинский университет

Assistant Professor of the Department of Pharmacology of Kuban State Medical University, Krasnodar, Russia; е-mail: alina_sergeeva_v@mail.ru; ORCID ID https://orcid.org/0000-0003-4335-2156. Author's contribution: experimentation; analysis and interpretation of research results; participation in scientific design.

Алина В. Корнецкая, Кубанский государственный медицинский университет

3rdyear student of the Faculty of Medicine of Kuban State Medical University, Krasnodar, Russia; е-mal: alinaleigh@mail.ru; ORCID ID https://orcid.org/0009-0007-7452-2871. Author's contribution: experimentation; analysis and interpretation of research results; participation in scientific design.

Николай Е. Коровайкин, Кубанский государственный медицинский университет

3rdyear student of the Faculty of Medicine of Kuban State Medical University, Krasnodar, Russia; е-mail: nikkoro@bk.ru; ORCID ID https://orcid.org/0009-0004-9543-7906. Author's contribution: experimentation; analysis and interpretation of research results; participation in scientific design.

Загрузки

Опубликован

13.02.2024

Как цитировать

Galenko-Yaroshevsky PA, Shelemekh OV, Popkov VL, Zadorozhniy AV, Nektarevskaya IB, Bunyatyan ND, Murashko RA, Lebedeva SA, Zelenskaya AV, Uvarov AV, Gulevskaya ON, Alukhanyan LO, Glechyan TR, Sergeeva AV, Kornetskaya AV, Korovaykin NE (2024) Study of the anti-inflammatory, analgesic, ulcerogenic and anti-ulcerogenic activity of N-isopropenylimidazole zinc complex derivative. Research Results in Pharmacology 10(1): 23–43. https://doi.org/10.18413/rrpharmacology.10.443

Выпуск

Том 10 № 1 (2024)

Раздел

Экспериментальная фармакология

Лицензия

Copyright (c) 2024 Pavel A. Galenko-Yaroshevsky, Olga V. Shelemekh, Viktor L. Popkov, Andrey V. Zadorozhniy, Irina B. Nektarevskaya, Natalia D. Bunyatyan, Roman A. Murashko, Svetlana А. Lebedeva, Anait V. Zelenskaya, Aleksandr V. Uvarov, Olga N. Gulevskaya, Lusine O. Alukhanyan, Tereza R. Glechyan, Alina V. Sergeeva, Alina V. Kornetskaya, Nikolay E. Korovaykin

Лицензия Creative Commons

Это произведение доступно по лицензии Creative Commons «Attribution» («Атрибуция») 4.0 Всемирная.