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

Darya Pon Kina,Sergey Kuranov,Mikhail Khvostov, Nataliya Zhukova,Yulia Meshkova,Mariya Marenina,Olga Luzina, Tatyana Tolstikova, Nariman Salakhutdinov

Molecules (Basel, Switzerland)(2023)

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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)-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-induced toxic liver damage.
FFAR1 agonist,bornyl derivatives,carbon tetrachloride,hepatoprotective effect,liver injury
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