Approbation of a Model of Fat Liver Disease Induced by Orotic Acid

Abstract

Introduction. For the treatment of non-alcoholic fatty liver disease (NAFLD), hepatoprotective drugs are actively used. The existing models of non-alcoholic fatty liver disease used to study the effectiveness of medicinal products are characterized by a long duration of recovery and high mortality of test systems, in connection with which, the actual task is to test the screening model of this pathology. A number of studies have shown the hepatotoxic activity of orotic acid (OK), species-specific for rats, leading to the development of NAFLD.Aim. Approbation of the NAFLD model induced by orotic acid on 2 rodent species (mice and rats), research of the reversibility of pathology under the action of a reference drug (ursodeoxycholic acid – UDCA).Materials and methods. The reseacrh was conducted on outbred male rats weighing 260–265 g (n = 21) and inbred male mice of the C57BL/6 line weighing 16–18 g (n = 30). By randomization, the rats were divided into 3 groups (7 rats each): group 1 – intact animals; group 2 – NAFLD model; group 3 – NAFLD + UDCA model, mice were divided into 2 groups (10 and 20 mice, respectively): group 1 – intact animals; group 2 – NAFLD model. NAFLD was modeled by a high-carbohydrate diet with orotic acid (75 % standard feed, 24 % fructose and 1 % potassium orotate). UDCA was administered after the first control point 1 time a day through a probe in terms of 150 mg/kg. Biochemical and histological examination was carried out.Results and discussion. It was revealed that a high-carbohydrate diet with the addition of 1 % potassium orotate for 4 weeks causes moderate balloon dystrophy, mild hepatitis and an increase in the content of alanine aminotransferase and aspartate aminotransferase in the blood of rats and less significant changes in mice. Low animal mortality was also noted. The use of UDCA on the claimed model causes a decrease in the severity of liver dystrophy and a decrease in the level of liver enzymes in the blood.Conclusion. Based on the conducted experiments, rats turned out to be the optimal test system on the reproduced model, and a high-fat diet with the addition of orotic acid allows screening studies of drugs with hepatotropic activity.