Hepatoprotective effect of the N-alkylated isobornylamine against CCl₄-induced chronic liver damage in mice

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease caused by impaired lipid and carbohydrate metabolism and characterized by fatty degeneration, necrosis, inflammation and fibrosis of hepatocytes. There are currently no approved drugs for the treatment of NAFLD, so their search remains an urgent task for present pharmacology. Previously, N-alkylated isobornylamine (compound 1), a GPR40 agonist, at a dose of 30 mg/kg was shown to resolve of fatty liver degeneration of C57Bl/6^Ay mice improving glucose tolerance. Based on this, we continued to study the hepatoprotective effect of compound 1 on CCl₄ - induced chronic hepatotoxicity model in CD-1 mice. The compound 1 was administered per os at doses of 60, 90, 120, 150 mg/kg daily for 3 weeks as well as the reference drug Silymarin at a dose of 100 mg/kg. At the end of the experiment, a biochemical blood assay was carried out, which showed that compound 1 dose-dependently reduces ALT, AST and ALKP. According to the results of a histological and morphometry liver examination, the compound 1 was found to reduce the severity of degenerative-necrotic changes in hepatocytes. More pronounced improvements in doses of 120 and 150 mg/kg were noted. Thus, isobornylamine derivative exhibit a hepatoprotective effect not only in metabolic liver injury, but also in CCl₄ - induced chronic liver damage.