This paper focuses on fundamental morphological developmental disorders of general embryogenesis and toxic metal-induced changes in rat kidneys in prenatal and early postnatal period (10 days after birth). The presented results were expected after the daily isolated alkaline of cadmium salts (chloride / citrate) infusion in combined oral administration, under the terms of microelements correction with citrates. The experimental research was carried out on the female lab rats of Wistar linne. The morphological materials of the study were embryos and embryonic kidneys on the 13th and 20th days of gestation, also the rat kidneys on the 10th day of postnatal development.
The steps proceed in such ways as determination of the cadmium and zinc accumulation levels in the kidneys of embryos and morphological analysis of structural kidneys changes (massometric analysis and microscopic examination, immunohistochemical studies).
In order to estimate embryotoxicity and search for new possible bioanthogonists, the mortality rates were calculated. There was used the method of polyelement analysis in rat embryos for all groups.
As shown by the analysis of the obtained data of cadmium accumulation in the kidneys of embryos using the polyelement method, the highest level of cadmium accumulation was determined by isolated exposure to cadmium chloride (0.0084 ± 0.000044 μg / g), which was 12 times higher than the control values (0.0007 ± 0 , 000051μg / g). Isolated administration of cadmium citrate (0.0059 ± 0.000032 μg /g) led to the increase in renal cadmium levels by 8.4 times compared to control values, but this figure was 1.4 times lower than the isolated effect of cadmium chloride. When exposed to cadmium salts, the level of zinc accumulation increases in both experimental groups. In the groups of combined administration, the level of cadmium accumulation was significantly lower (p≤0.05) for the following indicator of isolated exposure to cadmium: 1.8 times in combination with cerium citrate and 4 times with iron citrate, indicating the bioantagonistic properties of cerium citrates and of iron relative to the accumulation of cadmium chloride in the kidneys of experimental animals when combined in an experiment on rats.
On the 13th day of embryogenesis, morphometric indices of mesonephros thickness in the control were on average 186.50 ± 13.74 μm, and when exposed to cadmium chloride, a thickening of the nephrogenic tissue was observed to 248.68 ±26.31 μm and the decrease in the number of metanephridia with dilatation. The effect of isolated administration of cadmium citrate led to a decrease in the thickness of the mesonephros to 139.94 ± 14.12 μm. Similar tendencies were also observed in the morphometric characteristics of the mesonephric duct. Thus, the effect of cadmium salts on the development of embryos’ kidneys indirectly receiving cadmium was diverse: the effect of cadmium chloride led to the increase in the mesonephros and mesonephric duct, and the effect of cadmium citrate reduced the studied indicators. In the groups of combined administration, the thickness of the mesonephros approached the control.
The use of the immunohistochemical marker Ki67 revealed the diversity of proliferative processes in the renal parenchyma of both experimental groups. Isolated administration of cadmium chloride leads to the decrease in the activity of proliferative processes in the kidneys of rat fetuses on the 20th day of embryogenesis. In the group of isolated administration of cadmium citrate, the accumulation of the marker Ki67 had a pronounced gradient: the intensive accumulation in the cortical substance of the kidneys, and in the cerebral part of its accumulation was reduced by control values. The accumulation of the actin marker α-sma in all three groups showed the decrease in the level of expression of this marker, which we regarded as a negative effect of cadmium salts on renal angiogenesis, but the shifts in the accumulation of the marker were multidirectional. When exposed to cadmium chloride, the decrease in the level of α-sma accumulation in the brain substance was determined, which indicates the decrease in the processes of angiogenesis in the kidneys compared to the control. And when exposed to cadmium citrate, on the contrary, the layer of brain substance had the same level of accumulation as in the control, but the formation of cortical vessels differed in the direction of reduction.
The combined administration of citrates of the studied microelements led to the restoration of histological and morphometric structures of the kidneys, which indicated their modifying effect on the nephrotoxicity and embryotoxicity of cadmium salts. The obtained results revealed new cadmium bioantogonists. According to the obtained results, the Patent of Ukraine for reducing the embryotoxicity of cadmium chloride in animals was obtained
