Pharmacological Analysis of the Mechanisms of Action and Correction of Isoniazid-induced Toxicity in NAT2-humanized Transgenic Mice
https://doi.org/10.33647/2074-5982-22-1-38-47
Abstract
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.
About the Authors
N. V. Petrova
Scientific Center of Biomedical Technologies of the Federal Medical and Biological Agency of Russia
Russian Federation
Russian Federation
143442, Russian Federation, Moscow Region, Krasnogorsk District, Svetlye Gory Village, 1
N. N. Karkischenko
Scientific Center of Biomedical Technologies of the Federal Medical and Biological Agency of Russia
Russian Federation
Russian Federation
143442, Russian Federation, Moscow Region, Krasnogorsk District, Svetlye Gory Village, 1
I. A. Pomytkin
Scientific Center of Biomedical Technologies of the Federal Medical and Biological Agency of Russia
Russian Federation
Russian Federation
143442, Russian Federation, Moscow Region, Krasnogorsk District, Svetlye Gory Village, 1
V. V. Slobodenyuk
Scientific Center of Biomedical Technologies of the Federal Medical and Biological Agency of Russia
Russian Federation
Russian Federation
143442, Russian Federation, Moscow Region, Krasnogorsk District, Svetlye Gory Village, 1
S. B. Kurashev
Scientific Center of Biomedical Technologies of the Federal Medical and Biological Agency of Russia
Russian Federation
Russian Federation
143442, Russian Federation, Moscow Region, Krasnogorsk District, Svetlye Gory Village, 1
M. A. Savina
Scientific Center of Biomedical Technologies of the Federal Medical and Biological Agency of Russia
Russian Federation
Russian Federation
143442, Russian Federation, Moscow Region, Krasnogorsk District, Svetlye Gory Village, 1
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Review
For citations:
Petrova N.V., Karkischenko N.N., Pomytkin I.A., Slobodenyuk V.V., Kurashev S.B., Savina M.A. Pharmacological Analysis of the Mechanisms of Action and Correction of Isoniazid-induced Toxicity in NAT2-humanized Transgenic Mice. Journal Biomed. 2026;22(1):38-47. (In Russ.) https://doi.org/10.33647/2074-5982-22-1-38-47
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