vedomostiregmedРегуляторные исследования и экспертиза лекарственных средствRegulatory Research and Medicine Evaluation3034-30623034-3453Federal State Budgetary Institution ‘Scientific Centre for Expert Evaluation of Medicinal Products’ of the Ministry of Health of the Russian Federation (FSBI ‘SCEEMP’)10.30895/1991-2919-2021-11-160-166vedomostiregmed-372Research ArticleОБЗОРЫREVIEWSЭкспериментальные модели клеточных линий для скрининга нефротоксичностиExperimental Cell Line Models for Nephrotoxicity Screeninghttps://orcid.org/0000-0002-3733-6822МазеркинаИ. А.MazerkinaI. A.

Мазеркина Ирина Анатольевна, кандидат медицинских наук,

Петровский б-р, д. 8, стр. 2, Москва, 127051

Irina A. Mazerkina, Cand. Sci. (Med.),

8/2 Petrovsky Blvd, Moscow 127051

mazerkina@expmed.ruhttps://orcid.org/0000-0002-6150-5796ЕвтеевВ. А.EvteevV. A.

Евтеев Владимир Александрович,

Петровский б-р, д. 8, стр. 2, Москва, 127051

Vladimir A. Evteev,

8/2 Petrovsky Blvd, Moscow 127051

evteev@expmed.ruhttps://orcid.org/0000-0001-7024-5546ПрокофьевА. Б.ProkofievA. B.

Прокофьев Алексей Борисович, доктор медицинских наук,

Петровский б-р, д. 8, стр. 2, Москва, 127051

Aleksey B. Prokofiev, Dr. Sci. (Med.),

8/2 Petrovsky Blvd, Moscow 127051

prokofiev@expmed.ruhttps://orcid.org/0000-0003-1009-9609МуслимоваО. В.MuslimovaO. V.

Муслимова Ольга Валерьевна, кандидат медицинских наук,

Петровский б-р, д. 8, стр. 2, Москва, 127051

Olga V. Muslimova, Cand. Sci. (Med.),

8/2 Petrovsky Blvd, Moscow 127051

 

muslimova@expmed.ruhttps://orcid.org/0000-0003-1972-4386ДемченковаЕ. Ю.DemchenkovaE. Yu.

Демченкова Елена Юрьевна, кандидат фармацевтических наук,

Петровский б-р, д. 8, стр. 2, Москва, 127051

Elena Yu. Demchenkova, Cand. Sci. (Pharm.),

8/2 Petrovsky Blvd, Moscow 127051

demchenkova@expmed.ruФедеральное государственное бюджетное учреждение «Научный центр экспертизы средств медицинского применения» Министерства здравоохранения Российской ФедерацииРоссияScientific Centre for Expert Evaluation of Medicinal ProductsRussian Federation202116082021113160166Copyright © Мазеркина И.А., Евтеев В.А., Прокофьев А.Б., Муслимова О.В., Демченкова Е.Ю., 20212021Мазеркина И.А., Евтеев В.А., Прокофьев А.Б., Муслимова О.В., Демченкова Е.Ю.Mazerkina I.A., Evteev V.A., Prokofiev A.B., Muslimova O.V., Demchenkova E.Y.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.vedomostincesmp.ru/jour/article/view/372

Цель работы – обзор клеточных моделей для экспериментальной оценки нефротоксичности ЛС in vitro, по данным литературных источников. Нефротоксичность является причиной отказа от дальнейшей разработки нового лекарственного средства в 2% случаев по результатам доклинических исследований in vivo на лабораторных животных и в 19% – после исследований 3 фазы. Прогнозирование токсичности на клеточных моделях позволит сэкономить средства при разработке лекарственного средства, а также сократить/избежать исследований на лабораторных животных. В настоящее время не существует официальных международных рекомендаций по исследованию нефротоксичности in vitro, тема находится в интенсивной разработке. Основной мишенью токсического поражения почек являются эпителиальные клетки проксимальных канальцев, поэтому основные исследования направлены на создание клеточных линий, характеризующихся стабильными функциональными качествами этих клеток. При моделировании нефротоксичности также важным является выбор релевантных методов и конечных точек тестов, которые могли бы учитывать возможные механизмы токсического действия. В обзоре рассматриваются существующие линии эпителиальных клеток проксимального почечного канальца человека и современные методики оценки цитотоксичности. Дальнейшая перспектива разработки клеточных моделей для скрининга нефротоксичности – оптимизация и стандартизация систем in vitro, которые позволили бы на доклиническом этапе прогнозировать нефротоксичность лекарственного средства in vivo.

The aim of the study was to review literature data on cell models for experimental assessment of drug nephrotoxicity in vitro. Because of nephrotoxicity, 2% of new investigational medicinal products are discarded at the stage of preclinical in vivo studies in laboratory animals, and 19%—after phase 3 clinical trials. Prediction of toxicity in cell models could make drug development more cost-effective and help to reduce/avoid animal testing. At present, there are no official international guidelines for assessment of nephrotoxicity in vitro, but there is a lot of research underway. The main toxicity target in kidneys is renal proximal tubule epithelial cells, therefore the main research is focused on the development of renal proximal tubule epithelial cell lines with stable functional characteristics. Another important aspect in nephrotoxicity modeling is the choice of relevant test methods and end points which would reflect potential toxicity mechanisms. The paper reviews existing human renal proximal tubule epithelial cell lines and current test methods for assessing cytotoxicity. Promising areas for future development of cell models for nephrotoxicity assessment— are optimisation and standardisation of in vitro systems that would help to make preclinical predictions of drug nephrotoxicity in vivo.  

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