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Hepatoprotective Effect of a New FFAR1 Agonist—N-Alkylated Isobornylamine

Free fatty acid receptor-1 (FFAR1) is one of the possible therapeutic targets in the search for new hepatoprotective drugs. FFAR1 agonists were found to have hypolipidemic, antifibrotic, anti-inflammatory, antiproliferative and antioxidant effects in addition to hypoglycemic action. In this work, we...

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Autores principales: Pon`kina, Darya, Kuranov, Sergey, Khvostov, Mikhail, Zhukova, Nataliya, Meshkova, Yulia, Marenina, Mariya, Luzina, Olga, Tolstikova, Tatyana, Salakhutdinov, Nariman
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9823450/
https://www.ncbi.nlm.nih.gov/pubmed/36615590
http://dx.doi.org/10.3390/molecules28010396
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author Pon`kina, Darya
Kuranov, Sergey
Khvostov, Mikhail
Zhukova, Nataliya
Meshkova, Yulia
Marenina, Mariya
Luzina, Olga
Tolstikova, Tatyana
Salakhutdinov, Nariman
author_facet Pon`kina, Darya
Kuranov, Sergey
Khvostov, Mikhail
Zhukova, Nataliya
Meshkova, Yulia
Marenina, Mariya
Luzina, Olga
Tolstikova, Tatyana
Salakhutdinov, Nariman
author_sort Pon`kina, Darya
collection PubMed
description Free fatty acid receptor-1 (FFAR1) is one of the possible therapeutic targets in the search for new hepatoprotective drugs. FFAR1 agonists were found to have hypolipidemic, antifibrotic, anti-inflammatory, antiproliferative and antioxidant effects in addition to hypoglycemic action. In this work, we conducted a study of the hepatoprotective effect of the compound QS-528 (previously discovered as an agonist of FFAR1) at doses of 60, 90, 120 and 150 mg/kg on carbon tetrachloride (CCl(4))-induced liver injury. At the end of the experiment, a biochemical blood assay demonstrated that the introduction of QS-528 dose-dependently reduces the levels of liver enzymes (AST, ALT and ALKP). Histological and morphometric studies of animals’ livers treated with QS-528 at doses of 120 and 150 mg/kg showed a decrease in degenerative/necrotic changes in hepatocytes and an increase in the regenerative activity of the liver. In addition, no toxicity at a single oral dose of 1000 mg/kg and an increase in HepG2 cell viability in vitro were found. Thus, the compound QS-528 was found to exhibit a hepatoprotective effect against CCl(4)-induced toxic liver damage.
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spelling pubmed-98234502023-01-08 Hepatoprotective Effect of a New FFAR1 Agonist—N-Alkylated Isobornylamine Pon`kina, Darya Kuranov, Sergey Khvostov, Mikhail Zhukova, Nataliya Meshkova, Yulia Marenina, Mariya Luzina, Olga Tolstikova, Tatyana Salakhutdinov, Nariman Molecules Article Free fatty acid receptor-1 (FFAR1) is one of the possible therapeutic targets in the search for new hepatoprotective drugs. FFAR1 agonists were found to have hypolipidemic, antifibrotic, anti-inflammatory, antiproliferative and antioxidant effects in addition to hypoglycemic action. In this work, we conducted a study of the hepatoprotective effect of the compound QS-528 (previously discovered as an agonist of FFAR1) at doses of 60, 90, 120 and 150 mg/kg on carbon tetrachloride (CCl(4))-induced liver injury. At the end of the experiment, a biochemical blood assay demonstrated that the introduction of QS-528 dose-dependently reduces the levels of liver enzymes (AST, ALT and ALKP). Histological and morphometric studies of animals’ livers treated with QS-528 at doses of 120 and 150 mg/kg showed a decrease in degenerative/necrotic changes in hepatocytes and an increase in the regenerative activity of the liver. In addition, no toxicity at a single oral dose of 1000 mg/kg and an increase in HepG2 cell viability in vitro were found. Thus, the compound QS-528 was found to exhibit a hepatoprotective effect against CCl(4)-induced toxic liver damage. MDPI 2023-01-03 /pmc/articles/PMC9823450/ /pubmed/36615590 http://dx.doi.org/10.3390/molecules28010396 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Pon`kina, Darya
Kuranov, Sergey
Khvostov, Mikhail
Zhukova, Nataliya
Meshkova, Yulia
Marenina, Mariya
Luzina, Olga
Tolstikova, Tatyana
Salakhutdinov, Nariman
Hepatoprotective Effect of a New FFAR1 Agonist—N-Alkylated Isobornylamine
title Hepatoprotective Effect of a New FFAR1 Agonist—N-Alkylated Isobornylamine
title_full Hepatoprotective Effect of a New FFAR1 Agonist—N-Alkylated Isobornylamine
title_fullStr Hepatoprotective Effect of a New FFAR1 Agonist—N-Alkylated Isobornylamine
title_full_unstemmed Hepatoprotective Effect of a New FFAR1 Agonist—N-Alkylated Isobornylamine
title_short Hepatoprotective Effect of a New FFAR1 Agonist—N-Alkylated Isobornylamine
title_sort hepatoprotective effect of a new ffar1 agonist—n-alkylated isobornylamine
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9823450/
https://www.ncbi.nlm.nih.gov/pubmed/36615590
http://dx.doi.org/10.3390/molecules28010396
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