Bilyshko D. Morphofunctional changes of the liver under the influence of cadmium salts in rat embryogenesis (anatomical and experimental study)

The dissertation is devoted to the study of morphological bases of disorders of the general course of embryogenesis and establishment of morphological changes of rat embryo liver structures in prenatal and early postnatal period of ontogenesis under the influence of cadmium chloride and citrate at isolated introduction and under conditions of selenium citrate and germanium citrate correction. The experimental study was performed on laboratory rats, the introduction of the studied factors was performed on females intragastrically daily (chronic exposure) from the first day to the end of pregnancy. The morphological material of the study were embryos and liver of embryos on the 13th and 20th day of gestation and 10-day-old rats. The use of embryological, statistical, histological and immunohistochemical methods allowed to study the indicators of all types of embryonic mortality and the main changes in the morphogenesis of embryonic liver under the action of solutions of cadmium chloride / cadmium citrate at a dose of 1.0 mg / kg with isolated administration of (0.1 mg / kg), or selenium citrate (0.1 mg / kg). The use of the method of polyelement analysis with atomic emission allowed to determine and compare the level of cadmium and zinc accumulation in the liver of embryos at the end of embryogenesis of all experimental groups. Morphometric parameters of the liver parenchyma of rats of the 10th day of life after exposure to cadmium citrate showed an unexpected direction of change compared to the control and the group of exposure to cadmium chloride. The average length of the portal lobe wall had no significant difference with the control and was equal to 308.21 ± 16.12 μm, but the diameter of the central vein of the hepatic lobe increased almost twice (by 98.3%) and was 83.49 ± 3.56 μm. Thus, the effect of cadmium citrate had a pronounced response from the vessels of the liver. The structure of the hepatic lobe itself was disturbed, namely: most of the liver beams merged and changed the radial course in the lobe structure. The liver parenchyma itself was compacted, with a large number of stromal components with local stratification. In the groups of simultaneous administration of cadmium with selenium citrate / germanium citrate, the liver lobes did not have significant differences in the studied parameters, approaching the control. The use of immunohistochemical markers revealed the influence of cadmium salts on the course of such basic histogenetic processes as proliferation and vasculogenesis of the liver parenchyma. As shown by the result of comparing the marker of proliferation Ki67, the highest degree of accumulation of this marker was determined when exposed to cadmium chloride, which explains the obtained morphometric data. When exposed to cadmium citrate, the accumulation of the proliferative marker exceeded the control, however, the compactness of the liver beams and the increase in their thickness differed from the liver parenchyma when exposed to cadmium chloride New anatomical and experimental data on the degree of embryotoxicity of cadmium chloride and cadmium citrate, the level of their accumulation in the liver of embryos under the influence of the same doses in chronic intoxication of female rats. Selenium citrate and germanium citrate have been shown for the first time to reduce the level of embryotoxicity of cadmium when combined in all respects (average embryo population, total embryonic mortality, preimplantation and postimplantation embryo mortality). It was first shown that the combined administration of selenium and germanium citrates with cadmium reduces the level of cadmium accumulation by the liver of the rat fetus on the 20th day of embryonic development. The degree of novelty of the obtained results is confirmed by the patent obtained by the results of calculations of experimental research (patent № 140771 UA) as a way to reduce embryotoxicity of cadmium chloride using the detoxifying substance germanium citrate, which determined the degree of compensatory action. intoxication. The bioantagonistic properties of selenium and germanium citrates with respect to embryotoxic and hepatotoxic properties of cadmium have been experimentally revealed. The obtained data are the basis for further study of the effect of germanium and selenium citrates as substances with bioantagonistic properties against cadmium salts and the possible development of pharmacological treatments and prophylactics that may reduce the negative toxic effect of cadmium salts on embryogenesis and liver development in humans. man-made polluted regions or work in an environmentally unfavorable environment. The results of the influence of cadmium salts on the development of the liver allow us to explain the mechanism and timing or predict the occurrence of disorders of hepatogenesis when a pregnant woman lives in the area of cadmium intoxication, which are developed industrial regions.