scbmtБИОМЕДИЦИНАJournal Biomed2074-59822713-0428Scientific center of biomedical technologies of Federal Medical and Biological Agency10.33647/2074-5982-22-1-38-47scbmt-1829Research ArticleГЕНЕТИКА И ЭПИГЕНЕТИКА ЖИВОТНЫХ-БИОМОДЕЛЕЙGENETICS AND EPIGENETICS OF ANIMALS-BIOMODELSФармакологический анализ механизмов действия и коррекции токсических эффектов изониазида на гуманизированных трансгенных мышах NAT2Pharmacological Analysis of the Mechanisms of Action and Correction of Isoniazid-induced Toxicity in NAT2-humanized Transgenic MiceПетроваН. В.PetrovaN. V.

Петрова Наталья Владимировна

143442, Российская Федерация, Московская обл., Красногорский р-н, п. Светлые горы, 1

 

143442, Russian Federation, Moscow Region, Krasnogorsk District, Svetlye Gory Village, 1

m-sklad@yandex.ruКаркищенкоН. Н.KarkischenkoN. N.

Каркищенко Николай Николаевич, д.м.н.,проф., акад. РАРАН, чл.-корр. РАН

143442, Российская Федерация, Московская обл., Красногорский р-н, п. Светлые горы, 1

 

143442, Russian Federation, Moscow Region, Krasnogorsk District, Svetlye Gory Village, 1

niknik2808@yandex.ruПомыткинИ. А.PomytkinI. A.

Помыткин Игорь Анатольевич, д.б.н

143442, Российская Федерация, Московская обл., Красногорский р-н, п. Светлые горы, 1

 

143442, Russian Federation, Moscow Region, Krasnogorsk District, Svetlye Gory Village, 1

ipomytkin@mail.ruСлободенюкВ. В.SlobodenyukV. V.

Слободенюк Владимир Владимирович, к.б.н.,

143442, Российская Федерация, Московская обл., Красногорский р-н, п. Светлые горы, 1

 

143442, Russian Federation, Moscow Region, Krasnogorsk District, Svetlye Gory Village, 1

prof-v-iprim@mail.ruКурашевС. Б.KurashevS. B.

Курашев Сергей Борисович

143442, Российская Федерация, Московская обл., Красногорский р-н, п. Светлые горы, 1

 

143442, Russian Federation, Moscow Region, Krasnogorsk District, Svetlye Gory Village, 1

barrat220@gmail.comСавинаМ. А.SavinaM. A.

Савина Мария Анатольевна

143442, Российская Федерация, Московская обл., Красногорский р-н, п. Светлые горы, 1

 

143442, Russian Federation, Moscow Region, Krasnogorsk District, Svetlye Gory Village, 1

graff22@mail.ruФГБУН «Научный центр биомедицинских технологий ФМБА России»РоссияScientific Center of Biomedical Technologies of the Federal Medical and Biological Agency of RussiaRussian Federation2026140620262213847Copyright © Петрова Н.В., Каркищенко Н.Н., Помыткин И.А., Слободенюк В.В., Курашев С.Б., Савина М.А., 20262026Петрова Н.В., Каркищенко Н.Н., Помыткин И.А., Слободенюк В.В., Курашев С.Б., Савина М.А.Petrova N.V., Karkischenko N.N., Pomytkin I.A., Slobodenyuk V.V., Kurashev S.B., Savina M.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.scbmt.ru/jour/article/view/1829

Настоящая работа показывает, что исследования и скрининг новых, перспективных средств, применяемых в фармации и промышленности, целесообразно проводить на трансгенных мышах гуманизированной линии NAT2. Показано, что изониазид индуцирует транскрипцию гена NAT2hom, кодирующего N-ацетилтрансферазу 2, инактивирующую изониазид. Изониазид индуцирует транскрипцию гена NAT2mus, кодирующего N-ацетилтрансферазу, сходную с NAT1 человека, инактивирующую экзогенные биоактивные амины, подавляет транскрипцию гена SIRT1, кодирующего ядерную деацетилазу III класса, в мозге и почках, причем Лейтрагин, активатор транскрипции гена SIRT1, только частично снижает эффект изониазида. Изониазид влияет на транскрипцию гена TNF-α в зависимости от типа ткани.

This study demonstrates that NAT2-humanized mice are an effective biomodel for the research and screening of promising new drugs in pharmacy and industry. We show that isoniazid induces the transcription of the human NAT2 gene, which encodes N-acetyltransferase 2 (the enzyme responsible for isoniazid inactivation). Isoniazid also induces transcription of the mouse NAT2 gene, which encodes an N-acetyltransferase similar to human NAT1 that inactivates exogenous bioactive amines. Furthermore, isoniazid inhibits the transcription of the SIRT1 gene (encoding a class III nuclear deacetylase) in the brain and kidneys. Notably, Leytragin (SIRT1 transcription activator) only partially mitigates the effect of isoniazid. Finally, isoniazid affects TNF-α gene transcription depending on the type of tissue.

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