safetyriskБезопасность и риск фармакотерапииSafety and Risk of Pharmacotherapy2312-78212619-1164Federal State Budgetary Institution ‘Scientific Centre for Expert Evaluation of Medicinal Products’ of the Ministry of Health of the Russian Federation (FSBI ‘SCEEMP’)10.30895/2312-7821-2020-8-4-198-204safetyrisk-192Research ArticleОБЗОРЫREVIEWSВлияние транспортеров органических анионов на развитие нефротоксичности при применении нестероидных противовоспалительных средствEffect of Organic Anion Transporters on the Development of Nephrotoxicity in the Context of NSAIDs Usehttps://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/0000-0002-6150-5796ЕвтеевВ. 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/0000-0002-3733-6822МазеркинаИ. 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.ruНаучный центр экспертизы средств медицинского применения Министерства здравоохранения Российской ФедерацииРоссияScientific Centre for Expert Evaluation of Medicinal ProductsRussian Federation20200611202084198204Copyright © Муслимова О.В., Евтеев В.А., Мазеркина И.А., 20202020Муслимова О.В., Евтеев В.А., Мазеркина И.А.Muslimova O.V., Evteev V.A., Mazerkina I.A.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.risksafety.ru/jour/article/view/192

Нестероидные противовоспалительные средства (НПВС) широко применяются во всем мире в качестве болеутоляющих, жаропонижающих и противовоспалительных средств. Использование препаратов этой группы без соблюдения рекомендаций инструкции по их медицинскому применению повышает риск развития серьезных нежелательных реакций со стороны различных органов и систем. У 5–18% пациентов, получающих НПВС, развиваются нежелательные реакции, связанные с нарушениями функции почек. Важную роль в реализации негативного воздействия НПВС на почки играют белки-транспортеры органических анионов, посредством которых эти препараты экскретируются в мочу. Цель работы: анализ и систематизация данных научной литературы о роли транспортеров органических анионов в механизмах развития нефротоксичности при применении НПВС. Выявлено, что нежелательные реакции со стороны почек при приеме НПВС обусловлены несколькими механизмами, в том числе нарушением синтеза простагландинов из-за блокады циклооксигеназы 1 и/или 2 типов и прямым токсическим действием на эпителий почечных канальцев с развитием тубулярного некроза вследствие взаимодействия этих препаратов с транспортерами органических анионов. Кроме того, подавляя работу транспортеров органических анионов 1 и 3 типов, НПВС могут не только усиливать, но и уменьшать нефротоксические эффекты других лекарственных средств (при совместном применении), а также эндогенных и экзогенных токсинов. Поскольку применение НПВС имеет большое значение в терапии многих заболеваний (в том числе у пациентов пожилого возраста и с сопутствующей почечной патологией), исследование патогенеза нежелательных реакций со стороны почек, развивающихся с участием транспортеров лекарственных средств, будет продолжено.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used worldwide as pain relievers, antipyretics, and anti-inflammatory drugs. Failure to comply with the instructions for medical use of this group of drugs increases the risk of serious adverse reactions on the part of different organs and systems. From 5 to 18% of patients taking NSAIDs develop adverse reactions associated with impaired renal function. Organic anion transporter (OAT) proteins, which mediate the drug excretion with urine, have an important role to play in the NSAIDs adverse effect on kidneys. The aim of the study was to analyse and systematize scientific literature on the role of OATs in nephrotoxicity development in the context of NSAIDs use. It was revealed that adverse kidney reactions associated with NSAIDs are determined by several mechanisms, including inhibition of prostaglandin synthesis due to cyclooxeganse-1 and/or cyclooxeganse-2 blockade, and direct toxic effect on renal tubule epithelium followed by tubular necrosis due to NSAIDs interaction with OATs. Moreover, by suppressing OAT1 and OAT3, NSAIDs can not only enhance, but also reduce nephrotoxic effects of other medicines (when used together) and endogenous/exogenous toxins. Considering that NSAIDs are widely used in the treatment of various diseases (including in elderly patients and patients with concomitant renal diseases), it is still relevant to study mechanisms of adverse kidney reactions associated with drug transporters.

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