Исследование противовоспалительной, антиоксидантной, противомикробной и минерализующей активности металлокомплекса цинка производного N-изопропенилимидазола при экспериментальном эндодонто-пародонтальном поражении у крыс

Авторы

DOI:

https://doi.org/10.18413/rrpharmacology.10.515

Аннотация

Введение. Известно, что при комплексном лечении пациентов с заболеваниями зубочелюстной системы, включая эндодонто-пародонтальное поражение (ЭПП), находят широкое применение противовоспалительные, в том числе нестероидные противовоспалительные средства, и антибактериальные, в частности антибиотики и антисептики, лекарственные препараты, из которых первые нередко влекут за собой развитие гастро- и нейропатий, поражение почек и печени, а также сердечно-сосудистой системы, вторые, помимо серьезных побочных эффектов, – выработку устойчивой резистентности патогенных микроорганизмов и дисбактериоз. Это диктует необходимость поиска и разработки новых молекул, обладающих широким спектром терапевтического действия, направленным на блокирование инфекционно-воспалительного процесса и максимально возможного (в зависимости от тяжести поражения) восстановления функциональной способности зубов при ЭПП. Цель работы – изучить противовоспалительную, антиоксидантную, противомикробную и минерализующую активность металлокомплекса цинка производного N-изопропенилимидазола в условиях экспериментального эндодонто-пародонтального поражения у крыс.

Материалы и методы. Моделирование ЭПП в экспериментах на наркотизированных крысах осуществлялось следующим образом: первоначально проводилось вскрытие пульпарной полости нижних резцов, оставляя ее открытой для инфицирования, затем вызывалось воспаление пародонта лигатурным методом. Спустя 30 дней у животных развивалось ЭПП. Металлокомплекс цинка производного N-изопропенилимидазола (лабораторный шифр Пилим-1; приготовлен в виде геля), референс-препарат Метрогил Дента® (М-Д; гель стоматологический), а также сочетание Пилим-1 + М-Д наносили ежедневно в течение 14 дней на нижние резцы и соответствующие десна, а также закладывали в десневые карманы и пульпарные камеры, с предварительно частично извлеченной пульпой. После эвтаназии животных на 15 день экспериментов в гомогенатах десны исследовали активность эластазы, уреазы, каталазы, уровень малонового диальдегида и рассчитывали антиоксидантно-прооксидантный индекс, а в гомогенатах пульпы определяли активность эластазы, уреазы, щелочной и кислой фосфатаз, рассчитывали минерализующий индекс.

Результаты и их обсуждение. В десне при ЭПП Пилим-1 и, особенно, сочетание Пилим-1 + М-Д более значимо, чем М-Д, обладают выраженным противовоспалительным, антиоксидантным и противомикробным (снижают микробную обсемененность) действием. В пульпе при ЭПП Пилим-1 и, в большей мере, сочетание Пилим-1 + М-Д более выраженно, чем М-Д, оказывают противовоспалительное, противомикробное (снижают микробную обсемененность) и минерализующее действие. В механизмах терапевтического действия Пилима-1 и, особенно, сочетания Пилим-1 + М-Д в условиях ЭПП, по-видимому, важную роль играет способность их, помимо выявленного действия на исследованные метаболические процессы, оказывать также антигипоксический эффект, ингибирующее влияние на циклооксигеназу и 5-липооксигеназу. Кроме того, определенное значение может иметь наличие в структуре Пилима-1 цинка и имидазола, обладающих широким спектром биологической активности.

Заключение. Представленные результаты изучения Пилима-1 и его сочетания с М-Д свидетельствуют об их высокой лечебной эффективности, особенно при применении последнего, в условиях экспериментального ЭПП у крыс, что дает основание отнести     Пилим-1 и Пилим-1 + М-Д к потенциальным терапевтическим средствам, предназначенным для лечения ЭПП.

Графическая аннотация

Ключевые слова:

антиоксидантная активность, металлокомплекс цинка производного N-изопропенилимидазола, микробная обсемененность, минерализующая активность, противовоспалительная активность, эндодонто-пародонтальное поражение

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Вклад авторов

Павел А. Галенко-Ярошевский, Кубанский государственный медицинский университет

Pavel A. Galenko-Yaroshevsky, Corresponding member of the Russian Academy of Sciences, Doctor Habil. of Medical Sciences, Professor, Head of the Department of Pharmacology, Kuban State Medical University, Krasnodar, Russia; e-mail: Galenko.Yaroсhevsky@gmail.com, ORCID ID: https://orcid.org/0000-0003-3190-1437. The author developed a concept, formed the idea and direction of research, developed and designed the methodology, and formulated the key goals and objectives.

Иван И. Павлюченко, Кубанский государственный медицинский университет

Ivan I. Pavlyuchenko, Doctor Habil. of Medical Sciences, Professor, Head of the Department of Biology with the Course of Medical Genetics, Kuban State Medical University, Krasnodar, Russia; е-mail: inter-dekanat@mail.ru, ORCID ID: https://orcid.org/0000-0001-8019-9598. The author developed the key goals and objectives, conducted a critical review of the manuscript, analyzed it and provided valuable feedback.

Ольга В. Шелемех, Ростовский государственный медицинский университет

Olga V. Shelemekh, graduate student of the Department of Dentistry No. 4, Rostov State Medical University, Rostov-on-Don, Russia; e-mail: lioli777@yandex.ru, ORCID ID: https://orcid.org/0000-0003-3488-9971. The author took part in conducting research, collection of primary data, their analysis, statistical processing and structuring the article.

Борис А. Трофимов, Иркутский институт химии им. А.Е. Фаворского СО РАН

Boris A. Trofimov, Doctor Habil. of Chemical Sciences, Professor, member of the Russian Academy of Sciences, Head of the Laboratory of Unsaturated Heteroatom Compounds, A.E. Favorsky Irkutsk Institute of Chemistry, Irkutsk, Russia; e-mail: boris_trofimov@irioch.irk.ru,ORCID ID: https://orcid.org/0000-0002-0430-3215. The author developed the key goals and objectives, conducted a critical review of the manuscript, analyzed it and provided valuable feedback.

Лидия Н. Паршина, Иркутский институт химии им. А.Е. Фаворского СО РАН

Lidiya N. Parshina, Doctor Habil. of Chemical Sciences, senior specialist of the Laboratory of Unsaturated Heteroatom Compounds, A.E. Favorsky Irkutsk Institute of Chemistry, Irkutsk, Irkutsk, Russia; e-mail: parshina@irioch.irk.ru, ORCID ID: https://orcid.org/0000-0002-5516-6214. The author developed the key goals and objectives, conducted a critical review of the manuscript, analyzed it and provided valuable feedback.

Виктор Л. Попков, Кубанский государственный медицинский университет

Viktor L. Popkov, Doctor Habil. of Medical Sciences, Professor of the Department of Orthopedic Dentistry, Kuban State Medical University, Krasnodar, Russia; e-mail: vict.popkoff2015@yandex.ru, ORCID IDhttps://orcid.org/0000-0001-7362-0073. The author developed the key goals and objectives, conducted a critical review of the manuscript, analyzed it and provided valuable feedback.

Светлана А. Демьяненко, Ордена Трудового Красного Знамени Медицинский институт имени С.И. Георгиевского Крымского федерального университета имени В.И. Вернадского

Svetlana A. Demyanenko, Doctor Habil. of Medical Sciences, Professor, Head of the Department of Dentistry and Orthodontics, Medical Institute named after S.I. Georgievsky (winner of the Red Banner of Labor Award), V.I. Vernadsky Crimean Federal University, Simferopol, Russia; e-mail: dc.kvalitet@gmail.com, ORCID ID: https://orcid.org/0000-0002-2743-498X. The author developed the key goals and objectives, conducted a critical review of the manuscript, analyzed it and provided valuable feedback.

Олег В. Цымбалов, Кубанский государственный медицинский университет

Oleg V. Tsymbalov, Doctor Habil. of Medical Sciences, Professor, Professor of the Department of Surgical Dentistry and Maxillofacial Surgery, Kuban State Medical University, Krasnodar, Russia; e-mail: tsimbal_ov@mail.ru, ORCID ID: https://orcid.org/0000-0002-7970-323x. The author developed the key goals and objectives, conducted a critical review of the manuscript, analyzed it and provided valuable feedback.

Андрей В. Задорожный, Ростовский государственный медицинский университет

Andrey V. Zadorozhniy, Candidate of Medical Sciences, Associate Professor, Head of the Department of Dentistry No. 4, Rostov State Medical University, Rostov-on-Don, Russia; e-mail: stomvr1@gmail.com, ORCID IDhttps://orcid.org/0000-0001-9552-8542. The author edited and prepared the text of the manuscript, was engaged in developing research design, providing the resources for the research: consumables, animals, tools, computer equipment for analysis – and correction of the final draft of the manuscript

Анаит В. Зеленская, Кубанский государственный медицинский университет

Anait V. Zelenskaya, Candidate of Medical Sciences, Associate Professor of the Pharmacology Department, Kuban State Medical University, Krasnodar, Russia; e-mail: anait_06@mail.ru, ORCID ID: https://orcid.org/0000-0001-9512-2526. The author participated in research design, analyzed and interpreted the research results; prepared and edited the text of the manuscript.

Ирина Б. Нектаревская, Ростовский государственный медицинский университет

Irina B. Nektarevskaya, Candidate of Medical Sciences, Associate Professor of the Department of Dentistry No. 4, Rostov State Medical University, Rostov-on-Don, Russia; e-mail: nektir4546@mail.ru, ORCID ID: https://orcid.org/0009-0009-6733-9977. The author was engaged in conducting information retrieval research, animal handling and analysis of the obtained results.

Алина В. Сергеева, Кубанский государственный медицинский университет

Alina V. Sergeeva, teaching assistant, Department of Pharmacology, Kuban State Medical University, Krasnodar, Russia; e-mail: alina_sergeeva_v@mail.ru, ORCID ID: https://orcid.org/0000-0003-4335-2156. The author was engaged in developing research design, conducting research; analysis and interpretation of the obtained data.

Николай Е. Коровайкин, Кубанский государственный медицинский университет

Nikolay E. Korovaykin, 3rd-year student, Department of General Medicine, Kuban State Medical University, Krasnodar, Russia; e-mail: nikkoro@bk.ru, ORCID ID: https://orcid.org/0009-0004-9543-7906. The author was engaged in developing research design, conducting research; analysis and interpretation of the obtained data.

Светлана А. Лебедева, Первый Московский государственный медицинский университет имени И.М. Сеченова; Российский университет дружбы народов

Svetlana A. Lebedeva, Doctor Habil. of Biological Sciences, Associate Professor, Professor of the Department of Pharmacology, A.P. Nelyubin Institute of Pharmacy, Sechenov First Moscow State Medical University, Moscow, Russia; Department of Medical Elementology, RUDN University, Moscow, Russia; e-mail: Lebedeva502@yandex.ru, ORCID ID: https://orcid.org/0000-0001-8769-1040. The author developed the key goals and objectives, conducted a critical review of the manuscript and provided valuable feedback.

Опубликован

11.11.2024

Как цитировать

Galenko-Yaroshevsky PA, Pavlyuchenko II, Shelemekh OV, Trofimov BA, Parshina LN, Popkov VL, Demyanenko SA, Tsymbalov OV, Zadorozhniy AV, Zelenskaya AV, Nektarevskaya IB, Sergeeva AV, Korovaykin NE, Lebedeva SA (2024) Study of anti-inflammatory, antioxidant, antimicrobial and mineralizing effects of an N-isopropenylimidazole zinc metal complex derivative in experimental endodontic-periodontal lesions in rats. Research Results in Pharmacology 10(4): 1–13. https://doi.org/10.18413/rrpharmacology.10.515

Выпуск

Раздел

Экспериментальная фармакология

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