The Effect of Retinol Acetate on Liver Fibrosis Depends on the Temporal Features of the Development of Pathology

Abstract

The effect of vitamin A on the manifestations of liver fibrosis is controversial and establishing the causes of its multidirectional influence is an urgent problem. In the work, the functional characteristics of the liver with Cu-induced fibrosis were determined after the restoration of vitamin A to the control level at the F0/F1 stage. In animals with liver fibrosis, classical indicators of physiology, functional activity of the liver, histological, and hematological characteristics were determined; the content of calcium and ROS was determined in bone marrow cells. It was shown that in the liver with Cu-induced fibrosis, the restoration of vitamin A content to control values after per os injections of a retinol acetate solution at a dose of 0.10mg (300 IU)/100g of body weight in the early stages of this pathology development (Fо/F1) was accompanied by: a decrease in the number of immunocompetent cells in the bloodstream to control values; normalization of the amount of calcium ions and ROS in bone marrow cells; restoration to the control level of activity of alkaline phosphatase; an increase in the number of binuclear hepatocytes; and restoration of the dynamics of body weight growth in experimental animals, even against the background of the ongoing action of the hepatotoxic factor. We came to the conclusion that the multidirectional action of vitamin A, which occurs in liver fibrosis, depends not only on the concentration of vitamin A in the liverbut also on temporal characteristics of cellular and metabolic links involved in the adaptive response formation. It was suggested that knowledge of the initial temporal metabolic characteristics and the amount of vitamin A in the liver, taking into account the stages of fibrosis development, can be an effective way to restore the altered homeostatic parameters of the body.