1. Hepatoprotective Effect of a New FFAR1 Agonist-N-Alkylated Isobornylamine.
- Author
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Pon Kina D, Kuranov S, Khvostov M, Zhukova N, Meshkova Y, Marenina M, Luzina O, Tolstikova T, and Salakhutdinov N
- Subjects
- Animals, Liver, Antioxidants pharmacology, Hepatocytes, Carbon Tetrachloride toxicity, Plant Extracts pharmacology, Chemical and Drug Induced Liver Injury drug therapy, Chemical and Drug Induced Liver Injury prevention & control, Chemical and Drug Induced Liver Injury pathology, Liver Diseases drug therapy
- Abstract
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 CCl4 -induced toxic liver damage.- Published
- 2023
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