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Abstract <p>Previously, we created a modular nanotransporter (MNT) containing a monobody to Keap1, an intracellular protein inhibitor of the Nrf2 transcription factor that controls cellular protection from oxidative stress and is capable of interacting with Keap1 in hepatocytes and protect these cells from the effects of hydrogen peroxide. Oxidative liver damage by acetaminophen was used as a model to study the antitoxic effect of this MNT. Intraperitoneal injection of acetaminophen to mice resulted in an increase in the level of alanine aminotransferase and aspartate aminotransferase in the blood, as well as in liver edema. A significant decrease in the level of these enzymes in the blood, along with a decrease in liver edema, was observed after preliminary intravenous administration of MNT 2 h before the acetaminophen injection. The results obtained can be used as a basis for developing drugs to treat diseases associated with oxidative stress.</p>

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Modular Nanotransporters Containing Keap1 Monobodies Are Capable of Reducing the Toxic Effect of Acetaminophen on the Liver of Mice

  • 期刊论文

  • 发表日期：

    2025年4月11日

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  • Yu. V. Khramtsov,
  • A. A. Rosenkranz,
  • A. V. Ulasov,
  • T. A. Slastnikova,
  • T. N. Lupanova,
  • R. T. Alieva,
  • G. P. Georgiev,
  • A. S. Sobolev

摘要

Abstract

Previously, we created a modular nanotransporter (MNT) containing a monobody to Keap1, an intracellular protein inhibitor of the Nrf2 transcription factor that controls cellular protection from oxidative stress and is capable of interacting with Keap1 in hepatocytes and protect these cells from the effects of hydrogen peroxide. Oxidative liver damage by acetaminophen was used as a model to study the antitoxic effect of this MNT. Intraperitoneal injection of acetaminophen to mice resulted in an increase in the level of alanine aminotransferase and aspartate aminotransferase in the blood, as well as in liver edema. A significant decrease in the level of these enzymes in the blood, along with a decrease in liver edema, was observed after preliminary intravenous administration of MNT 2 h before the acetaminophen injection. The results obtained can be used as a basis for developing drugs to treat diseases associated with oxidative stress.