Possibilities of antifibrotic therapy and correction of cognitive disorders in experimentally induced severe liver fibrosis and cirrhosis in rats

Abstract

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 operator’s 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 180–200 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.

Keywords

bicyclol / chronic liver diseases / cirrhosis / encephalopathy / experimental model / fibrosis / liver biopsy / Morris labyrinth / rats / toxic hepatitis

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