Ontogenetic Approach to the Study of Mechanisms of Copper-Induced Liver Fibrosis

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.

Vitamin A intake forms resistance to hypervitaminosis A and affects the functional activity of the liver

“…3). Previously, it was shown during histological and biochemical studies that copper-induced fibrosis at such exposures is at the initial stages of development (F0, F1) [8,27]. It is known that at the initial stages of the liver fibrosis development, a decrease in activity ALT with its subsequent increase can be observed, and this characterizes the stages of pathology development [28].…”

The “Mix-Factor” is involved in the regulation of the organism's redox systems in the late stages of ontogenesis and affects the lifespan of animals

“…The mixing factor took part in the regulation of the functions of the redox system [14,15], the immune system [16], and several physiological functions in experimental animals [12]. Moreover, the effect of the mixing factor was age-dependent [17].…”