The influence of age on the effectiveness of complex therapy for experimental liver cirrhosis

Liver cirrhosis, a widespread disease worldwide, can be the result of various causes, such as hepatitis, obesity, and excessive alcohol consumption. The effectiveness of liver cirrhosis therapy is low, as the prescribed medications do not promote the regression of fibrosis or the regeneration of hepatocytes. Therefore, the research and development of new treatment methods for liver cirrhosis remains a pressing task. It is also important to consider age-related features in the course of the disease and responses to therapy. Purpose of the study was to investigate the therapeutic effectiveness of multicomponent therapy for liver cirrhosis in male Wistar rats of different ages. Material and methods. Experiments were performed on 12- and 36-week-old male Wistar rats. Liver cirrhosis was induced by 40% oil solution of CCl₄ to animals that received 5% ethanol solution and glucose which were freely available throughout the experiment. Polytherapy was carried out according to the following scheme: ketanserin from 85 to 95 days after the first administration of CCl₄ , reserpine on days 96 and 100, endothelial growth factor from 96 to 102 days, hepatocyte growth factor on day 100. The content of total and direct bilirubin, alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and cholesterol was measured in the blood serum. On histological preparations of the liver, inflammation, fibrosis and the degree of liver damage were assessed, the number of capillaries and the area of connective tissue were calculated. Results. With a course of administration of CCl₄ and alcohol in rats of both age groups, the development of multilobular cirrhosis, a decrease in the number of sinusoidal capillaries, an increase in the area of connective tissue were noted in the liver tissue and the levels of serum alkaline phosphatase, AST and ALT. Polytherapy of animals with the liver cirrhosis led to a decrease in the intensity of inflammatory infiltration of the liver parenchyma, a decrease in the area of connective tissue in the liver (by 22 % in 12-week-old rats, by 57 % in 36-week-old rats), an increase in the number of sinusoidal capillaries in the liver, a significant decrease in the levels of serum alkaline phosphatase, AST and ALT. In 36-week-old rats, normalization of total and direct bilirubin was observed. Conclusions. The promise of an integrated approach for the treatment of toxic liver cirrhosis in rats of different age groups has been demonstrated: polytherapy prevents the development of the inflammatory reaction, reduces the area of connective tissue and damage in the liver, helps normalize biochemical parameters of blood serum, while in 36-week old rats the effects of the drugs were more pronounced in comparison with 12-week-old animals.

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