Modular nanotransporters containing Keap1 monobodies are capable of reducing the toxic effect of acetaminophen on the liver of mice

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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 this 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 hours before the acetaminophen injection. The results obtained can serve as a basis for creating drugs aimed at treating diseases associated with oxidative stress.

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About the authors

Y. V. Khramtsov

Institute of Gene Biology, RAS

Author for correspondence.
Email: alsobolev@yandex.ru
Russian Federation, Moscow

A. A. Rosenkranz

Institute of Gene Biology, RAS; Lomonosov Moscow State University Moscow

Email: alsobolev@yandex.ru
Russian Federation, Moscow; Moscow

A. V. Ulasov

Institute of Gene Biology, RAS

Email: alsobolev@yandex.ru
Russian Federation, Moscow

T. А. Slastnikova

Institute of Gene Biology, RAS

Email: alsobolev@yandex.ru
Russian Federation, Moscow

T. N. Lupanova

Institute of Gene Biology, RAS

Email: alsobolev@yandex.ru
Russian Federation, Moscow

R. T. Alieva

Institute of Gene Biology, RAS

Email: alsobolev@yandex.ru
Russian Federation, Moscow

G. P. Georgiev

Institute of Gene Biology, RAS

Email: alsobolev@yandex.ru

Academician of the RAS

Russian Federation, Moscow

A. S. Sobolev

Institute of Gene Biology, RAS; Lomonosov Moscow State University Moscow

Email: alsobolev@yandex.ru
Russian Federation, Moscow; Moscow

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2. Fig. 1. SPECT/CT image of a C57Black/6J mouse one hour after intravenous administration of 125I-labeled MNT. (a) CT image; (b) SPECT image.

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3. Fig. 2. Dependence of 125I activity for 125I-labeled MNT in the mouse organism on time after its intravenous administration. The activity is taken without taking into account the thyroid gland, urinary bladder and stomach. The activity immediately after the administration of 125I-MNT is taken as 100%. The approximation of the data by an exponential dependence is shown.

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