Abstract

On the model of Cu-induced liver fibrosis, the relationship between the activity of prooxidant-antioxidant system, immune system parameters, liver morphology and several physiological parameters (body temperature and performance ability of the animals, taking into account their ages) was investigated. Classical biochemical, immunological, histological and physiological methods of investigation were used. The subjects of the study were male Wistar rats of 3-month (young) and 20-month (old) age. For the induction of liver fibrosis, experimental animals were successively injected with copper sulfate (three times at intervals of 24 hours at a dose corresponding to 33% of the lethal one). It was shown that after five days of sulfate copper administration inflammatory reactions in the liver, damage of the vessel epithelium, an increase in collagen content, and other morphological changes were detected. At this time, the content of lipid hydroperoxides in the liver and blood serum was increased, the activity of a number of antioxidant enzymes was reduced, and the activity of aconitase was two times less compared to values in the control group. These changes correlated with a decrease in the amount and activity of phagocytic cells in the blood of experimental animals. Inhibition of the general metabolism was accompanied by a decrease in body temperature, loss of body weight and performance ability. The relationship between a specific metabolic pattern in animals with Cu-induced fibrosis was age-dependent. The formed specific adaptive metabolic pattern is unstable, and in the future it can be realized in one of three possible adaptive strategies, the choice of which is influenced by age.

Highlights

  • According to the World Health Organization for the past 20 years, there has been a steady increase in chronic liver diseases of various etiologies, and mortality from liver diseases has reached the 4th place in the world [1] [2].the study of the mechanisms of induction of liver pathologies development is an urgent objective

  • For the induction of liver fibrosis, experimental animals were successively injected with copper sulfate

  • We have shown earlier that repeated successive administration of copper sulfate to the experimental animal was accompanied by the accumulation of copper ions by the liver, these ions were bound to copper-binding proteins of the liver cell cytosol, to mitochondria and the microsomal fraction [7]

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Summary

Introduction

According to the World Health Organization for the past 20 years, there has been a steady increase in chronic liver diseases of various etiologies, and mortality from liver diseases has reached the 4th place in the world [1] [2].the study of the mechanisms of induction of liver pathologies development is an urgent objective. As the liver is the central organ of homeostasis regulation and provides the functions of detoxification of various xenobiotics, a disturbance of the structure of the liver cells will induce systemic changes in the body. The essence of the problem of liver pathologies can be reduced to an understanding of the mechanisms for the formation of a metabolic strategy for the development of induced fibrosis. The solution of this problem is of great practical importance, since this knowledge can be the basis for developing new ways of liver pathologies treatment and understanding the fundamental mechanisms of reprogramming the activity of liver cells

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