Aim. To evaluate the antifibrotic effect of bicyclol with promising clinical effects on diffuse parenchymal liver diseases.Materials and methods: We have included 40 adult male Wistar rats (weight, 180 to 200g) with experimentally inducted toxic F3 stage liver fibrosis. Control group consisted of 16 rats that received standart chow, experimental group of 24 rats also received 30-day bicyclol supply. To evaluate the results we used histological, biochemical, molecular genetic and statistical methods.Results. In experimental group interlobular fibrosis was maintained in 4,16% (p<0,001) of cases after the end of the therapy, stromal fibrosis of portal tracts was observed in 62,5% (p<0,001) of cases. Periportal fibrosis detection rate in experimental group was 66,7% (p<0,001). Rats from experimental group showed regression of liver fibrosis to F1- F2 stage in 16,6% (METAVIR) whereas control group had F3 stage liver fibrosis in 62,5% (p <0,05). Statistically significant increase in ALT activity and decreased total protein levels in control group were observed. No changes in gut microbiome profile in experimental animals were found.Conclusion. Use of bicyclol led to pronounced suppression of liver fibrotic changes in laboratory animals and temporary decreased serum ALT level. Our study showed no link between therapeutic effects of the drug and gut microbiome status.

BACKGROUND: The main pathogenetic aspects of the correction of cognitive impairment of the brain and antifibrotic therapy against the background of experimentally induced severe fibrosis and cirrhosis of the liver in rats are considered. Viral hepatitis of various etiologies is one of the main problems of modern health care. The incidence of viral hepatitis is 30 million cases per year. Mortality from complications of acute viral hepatitis, such as cirrhosis of the liver and hepatocellular carcinoma, reaches 1.4 million cases per year. At the same time, in some cases, etiotropic therapy does not provide stabilization or regression of fibrotic changes in the liver tissue in comorbid patients, as well as in patients receiving antiviral therapy at the stages of severe fibrosis and compensated liver cirrhosis, which requires the search for new therapeutic approaches related to, first of all, with the possibility of influencing non-specific processes of fibrogenesis. Hepatic encephalopathy in such patients leads to the appearance of behavioral, cognitive and motor disorders of varying severity, thereby having a negative impact on the operators function in such professions as pilots, dispatchers, in a number of military specialties, etc. Thus, therapy aimed at the key links of pathogenesis often plays a decisive role in the treatment of liver diseases, especially in the later stages. AIM: To identify the presence and severity of cognitive impairment in rats with induced severe liver fibrosis and liver cirrhosis before and after therapy with Bicyclol and to assess the degree of its antifibrotic effect. MATERIALS AND METHODS: The study included 70 male Wistar rats weighing 180200 g, in which toxic fibrosis and cirrhosis of the liver were induced at stages F3 and F4. The control group consisted of 10 individuals who received a normal diet, the experimental group 24, who, in addition to the standard diet, were prescribed the drug Bicyclol. The assessment of cognitive impairment of the brain was carried out using a test with a hidden platform in the Morris water maze and statistical analysis. The evaluation of the results of the use of the drug was carried out using histological examination, methods of biochemical, molecular biological and statistical analysis. RESULTS: The use of the drug Bicyclol leads to a marked decrease in fibrotic changes in the liver tissue of experimental animals and was accompanied by a temporary decrease in the activity of alanine aminotransferase in blood serum. Against the background of the development of induced toxic fibrosis and cirrhosis of the liver in rats, cognitive dysfunctions of the brain were observed, which significantly decreased against the background of the use of the drug Bicyclol. CONCLUSION: Results The use of bicyclol for 4 weeks in laboratory animals with induced severe liver fibrosis led to a long-lasting decrease in the severity of fibrotic changes in liver tissue, as well as to the regression of cirrhosis in rats with liver cirrhosis. These changes were accompanied by a decrease in cognitive impairment in rats of these subgroups, as evidenced by an improvement in the estimated indicators when performing a control complex in a Morris water maze with a hidden platform.

The effectiveness and quality of liver biopsy in rats are applicable to the aspiration and automatic liver biopsy system. Histological examination of 240 biopsy specimens in 100% of cases identified portal tracts. The number of portal tracts to determine the stage of liver fibrosis in rats of the 1st group who underwent liver biopsy was performed using an 18 G aspirating needle from the puncture liver set (Menghini type), which is 4-5, you have the 2nd group, which one-time guillotine soft tissue biopsy with a semi-automatic action of 16G×20 cm, Italy) - 7-8 portal tracts. The average size of the biopsy in the 1st group is 0,5 cm, in the 2nd group - 1 cm. Thus, the automatic biopsy system allows you to get liver tissue in 100% of cases. At the same time, the automatic system eliminates the additional traumatization of experimental animals, as well as minimizes efforts to separate the biopsy material from the organ. In addition, the automated system for liver biopsy allows to evaluate 7-8 portal tracts with a biopsy size of 1 cm, this provides a reliable histological assessment of pathological changes in liver tissue to assess the stage of fibrosis and the activity of the inflammatory process over time.