pmedpharmФармация и фармакологияPharmacy & Pharmacology2307-92662413-2241Pyatigorsk Medical and Pharmaceutical Institute - branch of Volgograd State Medical Univer10.19163/2307-9266-2022-10-6-549-561pmedpharm-1220Research ArticleФАРМАКОЛОГИЯ И КЛИНИЧЕСКАЯ ФАРМАКОЛОГИЯPHARMACOLOGY AND CLINICAL PHARMACOLOGYСОЕДИНЕНИЕ ДФ-5 ЗАМЕДЛЯЕТ РАЗВИТИЕ ДИАБЕТИЧЕСКОЙ НЕФРОПАТИИ У КРЫСDF-5 COMPOUND DELAYS DEVELOPMENT OF DIABETIC NEPHROPATHY IN RATShttps://orcid.org/0000-0002-7185-4826СпасовА. А.SpasovA. A.

доктор медицинских наук, академик РАН, заведующий кафедрой фармакологии и биоинформатики, ФГБОУ ВО ВолгГМУ Минздрава России; заведующий лабораторией экспериментальной фармакологии ГБУ ВМНЦ

400131, Россия, г. Волгоград, пл. Павших Борцов, д. 1

Doctor of Sciences (Medicine), Academician of RAS, Head of the Pharmacology and Bioinformatics Department, Volgograd State Medical University; Head of the Laboratory of Experimental Pharmacology, Volgograd Medical Research Center

1, Pavshikh Bortsov Sq., Volgograd, Russia, 400131

aspasov@mail.ruhttps://orcid.org/0000-0003-2485-2139ЖуковскаяО. Н.ZhukovskayaO. N.

кандидат химических наук, старший научный сотрудник лаборатории органического синтеза НИИ ФОХ ФГАОУ ВПО ЮФУ

344090, Россия, г. Ростов-на-Дону, пр-т Стачки, д. 194/2

Candidate of Sciences (Chemistry), Senior researcher of the Organic Synthesis Laboratory, Institute of Physical and Organic Chemistry, Southern Federal University

Bldg 2, 194, Stachki Ave., Rostov-on-Don, Russia, 344090

zhukowskaia.ol@yandex.ruhttps://orcid.org/0000-0002-0162-0653РащенкоА. И.RashchenkoA. I.

кандидат фармацевтических наук, старший научный сотрудник лаборатории метаботропных лекарственных средств НЦИЛС, ФГБОУ ВО ВолгГМУ Минздрава России

400131, Россия, г. Волгоград, пл. Павших Борцов, д. 1

Candidate of Sciences (Pharmacy), Senior researcher of the Metabotropic Drugs Laboratory, Volgograd State Medical University; Volgograd Medical Research Center

1, Pavshikh Bortsov Sq., Volgograd, Russia, 400131

a.rashencko@yandex.ruhttps://orcid.org/0000-0003-0957-7087БригадироваА. А.BrigadirovaA. A.

кандидат медицинских наук, доцент кафедры фармакологии и биоинформатики ФГБОУ ВО ВолгГМУ Минздрава России; младший научный сотрудник лаборатории экспериментальной фармакологии ГБУ ВМНЦ

400131, Россия, г. Волгоград, пл. Павших Борцов, д. 1

Candidate of Sciences (Medicine), Associate Professor, Pharmacology and Bioinformatics Department, Volgograd State Medical University; Volgograd Medical Research Center

1, Pavshikh Bortsov Sq., Volgograd, Russia, 400131

a.brigadirova@gmail.comhttps://orcid.org/0000-0002-0162-0653ЛитвиновР. А.LitvinovR. A.

кандидат медицинских наук, старший научный сотрудник лаборатории метаботропных лекарственных средств НЦИЛС, ФГБОУ ВО ВолгГМУ Минздрава России; научный сотрудник лаборатории экспериментальной фармакологии ГБУ ВМНЦ

400131, Россия, г. Волгоград, пл. Павших Борцов, д. 1

Candidate of Sciences (Medicine), Senior researcher of the Metabotropic drugs Laboratory, Volgograd State Medical University; Researcher of the Laboratory of Experimental Pharmacology, Volgograd Medical Research Center

1, Pavshikh Bortsov Sq., Volgograd, Russia, 400131

litvinov.volggmu@mail.ruhttps://orcid.org/0000-0002-0670-1444ГуроваН. А.GurovaN. A.

доктор медицинских наук, профессор кафедры фармакологии и биоинформатики ФГБОУ ВО ВолгГМУ Минздрава России

400131, Россия, г. Волгоград, пл. Павших Борцов, д. 1

Doctor of Sciences (Medicine), Professor of the Pharmacology and Bioinformatics Department, Volgograd State Medical University

1, Pavshikh Bortsov Sq., Volgograd, Russia, 400131

gurova.vlgmed@mail.ruhttps://orcid.org/0000-0001-5351-6105СмирновА. В.SmirnovA. V.

доктор медицинских наук, заведующий кафедрой патологической анатомии ФГБОУ ВО ВолгГМУ Минздрава России

400131, Россия, г. Волгоград, пл. Павших Борцов, д. 1

Doctor of Sciences (Medicine), Head of the Pathological Anatomy Department, Volgograd State Medical University

1, Pavshikh Bortsov Sq., Volgograd, Russia, 400131

alexey-smirnov@rambler.ruhttps://orcid.org/0000-0002-4035-4108ПаньшинН. Г.Pan’shinN. G.

кандидат медицинских наук, доцент кафедры патологической анатомии ФГБОУ ВО ВолгГМУ Минздрава России

400131, Россия, г. Волгоград, пл. Павших Борцов, д. 1

Candidate of Sciences (Medicine), Associate Professor, Pathological Anatomy Department, Volgograd State Medical University

1, Pavshikh Bortsov Sq., Volgograd, Russia, 400131

panshin.nickolay@gmail.comАббасХ. С.А.AbbasH. S.A.

магистрант лаборатории органического синтеза НИИ ФОХ ФГАОУ ВПО ЮФУ

344090, Россия, г. Ростов-на-Дону, пр-т Стачки, д. 194/2

Master’s student of the Organic Synthesis Laboratory, Institute of Physical and Organic Chemistry, Southern Federal University

Bldg 2, 194, Stachki Ave., Rostov-on-Don, Russia, 344090

vip.haider89@gmail.ruhttps://orcid.org/0000-0002-9182-6101МорковникА. С.MorkovnikA. S.

доктор химических наук, главный научный сотрудник лаборатории органического синтеза НИИ ФОХ ФГАОУ ВПО ЮФУ

344090, Россия, г. Ростов-на-Дону, пр-т Стачки, д. 194/2

Doctor of Sciences (Chemistry), Chief Researcher, Organic Synthesis Laboratory, Institute of Physical and Organic Chemistry, Southern Federal University

Bldg 2, 194, Stachki Ave., Rostov-on-Don, Russia, 344090

asmork@mail.ruФедеральное государственное бюджетное образовательное учреждение высшего образования «Волгоградский государственный медицинский университет» Министерства здравоохранения Российской Федерации; Государственное бюджетное учреждение «Волгоградский медицинский научный центр»РоссияVolgograd State Medical University; Volgograd Medical Research CenterRussian FederationНаучно-исследовательский институт физической и органической химии федеральное государственное автономное образовательное учреждение высшего профессионального образования «Южный федеральный университет»РоссияInstitute of Physical and Organic Chemistry, Southern Federal UniversityRussian FederationФедеральное государственное бюджетное образовательное учреждение высшего образования «Волгоградский государственный медицинский университет» Министерства здравоохранения Российской ФедерацииРоссияVolgograd State Medical UniversityRussian Federation202213022023106549561Copyright © Спасов А.А., Жуковская О.Н., Ращенко А.И., Бригадирова А.А., Литвинов Р.А., Гурова Н.А., Смирнов А.В., Паньшин Н.Г., Аббас Х.С., Морковник А.С., 20232023Спасов А.А., Жуковская О.Н., Ращенко А.И., Бригадирова А.А., Литвинов Р.А., Гурова Н.А., Смирнов А.В., Паньшин Н.Г., Аббас Х.С., Морковник А.С.Spasov A.A., Zhukovskaya O.N., Rashchenko A.I., Brigadirova A.A., Litvinov R.A., Gurova N.A., Smirnov A.V., Pan’shin N.G., Abbas H.S., Morkovnik A.S.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/1220

Конечные продукты гликирования играют важную роль в развитии осложнений сахарного диабета. По этой причине замедление образования поперечных сшивок гликированных белков, как предполагается, является потенциальным терапевтическим подходом к лечению и профилактике осложнений заболевания, связанных с поражением сосудов.

Цель

Цель. Оценка способности нового антисшивающего соединения ДФ-5 влиять на количество конечных продуктов гликирования и коллагена в почках, на массу тела, уровни глюкозы и гликированного гемоглобина, а также на развитие ранних проявлений поражения почек у крыс со стрептозотоциновым сахарным диабетом.

Материалы и методы

Материалы и методы. Работа проведена на 40 самцах крыс Sprague-Dawley. Через 2 месяца после индукции диабета исследуемое вещество вводили внутрижелудочно (12,5 мг/кг) 1 р/сут в течение 28 дней с помощью зонда. Определяли уровень глюкозы и гликированного гемоглобина в крови, оценивали функцию почек, а также проводили гистологическое и иммуногистохимическое исследования тканей почек.

Результаты

Результаты. Регулярное внутрижелудочное введение ДФ-5 в течение 30 сут статистически значимо снижало уровень HbA1c в крови, но не влияло на уровень глюкозы в крови натощак. Соединение ДФ-5 существенно уменьшало протеинурию и предотвращало повреждение почек у экспериментальных животных за счет ограничения повреждений клубочков и канальцев. Было установлено, что соединение ДФ-5 замедляет повреждение почек на ранней стадии диабетической нефропатии, что сопровождается снижением количества конечных продуктов гликирования в ткани почек, улучшением их морфологической картины и функции.

Заключение

Заключение. Полученные результаты открывают возможность для разработки дополнительного терапевтического подхода к лечению диабетической нефропатии и, возможно, других осложнений сахарного диабета.

Advanced glycation end-products play an important role in the development of diabetic complications, so slowing down of glycated proteins’ cross-links formation have been suggested as a potential therapeutic option for the treatment of vascular diabetic complications and preventing their progression.

The aim of the work was to assess the influence of novel anticrosslinking agent DF-5 on the renal advanced glycation end-products and collagen contents, body weight, blood glucose and glycated hemoglobin levels and the development of early renal disease in streptozotocin-induced diabetic rats.

Materials and methods

Materials and methods. 40 male Sprague-Dawley rats were used in the study. Two months after inducing diabetes, the study substance was administered intragastrically once a day for 28 days (12.5 mg/kg). Measurements included the assessment of blood glucose and HbA1c levels, the evaluation of the renal function, and the results of histology and immunohistochemical staining of kidneys.

Results

Results. A repeated intragastric administration of DF-5 for 30 days significantly reduced the level of HbA1c in the blood, but did not affect the level of fasting blood glucose. DF-5 compound significantly reduced proteinuria and prevented kidney damage in experimental animals by limiting damage of the glomeruli and tubules. It was found that DF-5 inhibits the progression of an early renal dysfunction in rats with streptozotocin-induced diabetic nephropathy. This was associated with a decreased accumulation of advanced glycation end-products in the kidney, accompanied by the improvement of both renal morphology and function.

Conclusion

Conclusion. The results obtained provide investigators with additional therapeutic options for the treatment of diabetic nephropathy and possibly other complications of diabetes.

конечные продукты гликированияпоперечные сшивкиALT-711 (алагебриум)сахарный диабетдиабетическая болезнь почек (нефропатия)стрептозотоцин-индуцированный диабетadvanced glycation endproductscross-linksALT-711 (alagebrium)diabetes mellitusdiabetic kidney disease (nephropathy)streptozotocin-induced diabetesХимическая часть исследования выполнена в Институте органической и физической химии ФГАОУ ВПО «Южный федеральный университет» при финансовой поддержке Министерства науки и высшего образования Российской Федерации в рамках государственного задания, грант ФЕНВ-2020-0031 (0852-2020-0031). Биологическая часть исследования проведена при финансовой поддержке Российского научного фонда (проект 14-25-00139).The chemical part of this work was carried out in the Institute of Organic and Physical Chemistry, Southern Federal University with a financial support by the Ministry of Science and Higher Education of the Russian Federation in the framework of the state task, grant FENW-2020-0031 (0852-2020-0031). The biological part of this work was financially supported by the Russian Science Foundation (Project 14-25-00139).ReferencesSilva J.A.D., Souza E.C.F., Echazú Böschemeier A.G., Costa C.C.M.D., Bezerra H.S., Feitosa E.E.L.C. Diagnosis of diabetes mellitus and living with a chronic condition: participatory study // BMC Public Health. – 2018. – Vol. 18, No. 1. – Art. ID: 699. DOI:10.1186/s12889-018-5637-9Silva JAD, Souza ECF, Echazú Böschemeier AG, Costa CCMD, Bezerra HS, Feitosa EELC. Diagnosis of diabetes mellitus and living with a chronic condition: participatory study. 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The authors declare that there are no conflicts of interest present.