In the thesis, in vivo and in vitro experiments conducted a study of the long-term effects of low concentrations of cadmium on 3-month-old Wistar rats at the levels of the organism, a number of its organs, the cells and molecular.
Cd2+ was found to be at concentrations of 0.1 and 1 μg/kg/day, which are 5.5 and 8.3 times less than MRL and PTWI, respectively, with daily intake of rats for 5 weeks during the first 2 weeks stop the growth of animals, which resumes after 3 weeks of the experiment. Unlike the total weight of the body, the masses of all investigated organs - the heart, liver, kidneys, testes grow throughout the experiment with both doses of cadmium. Naturally, as a result, the massive coefficients of organs under the action of cadmium also increase. But cadmium still affects the growth of organs. The increase in both their mass by its action and, accordingly, the mass coefficients, is significantly slower than in the control. The revealed effect of suppressing the overall growth of animals and the growth retardation of parenchymal organs is obviously an integral consequence of cadmium in metabolic processes in different organ systems. To determine the metabolic disturbances that arise from this intervention, in the blood of rats, features of biochemical parameters characterizing the various components of the general metabolism were studied.
Under the influence of cadmium, the dynamics of the total protein content in the serum coincides qualitatively with the dynamics of their mass, and the dynamics in the serum of creatinine, urea, total cholesterol and triglycerides are completely opposite to the dynamics of the mass of animals and the content of total protein in their serum. In experimental animals, there is also a hypothyroid condition. In general, all this indicates that an important cause of weight loss in experimental animals is the degradation of skeletal muscle protein and the reduction of adipose tissue triggered by cadmium. From 3 weeks, despite its continuation, the compensatory systems restore the growth of animals.
Measurement of oxidative stress indicators showed that only a dose of 1 μg of Cd2+/kg of weight increased the content of 8-isoprostane in serum for 15 days and a half times, and at 36-th – almost tripled. The increase in the degree of carbonylation of proteins in serum at 36 days at a dose of 0.1 μg/kg of weight is 42 %, and at a dose of 1 μg/kg of weight – 58 %. Measurement of the activity of superoxidedismutase (SOD) under
conditions showed that SOD activity at the action of 0.1 μg Сd2+/ kg of body weight of animals did not increase by 15 days, and by action of 1 μg Сd2+/ kg slightly increased. On the 36th day after the action of these doses, the activity of this farm increased only by 10 % and 20 %. catalase (CAT) activity at a dose of 0.1 μg Сd2+ / kg of weight increases by 15 days by 60%, and by the 36th day the activity increase drops twice. 1 μg Сd2 +/ kg of the mass does not change CAT activity for the 15th day, and at the 36th it reduces it by 16 % compared to the control. This suggests that an important cause of the increasing development of oxidative stress in animals with a constant effect of cadmium ions is the lack of activity of SOD and CAT, especially in the dose of 1 μg Cd2+ / kg body weight.
The influence of cadmium on the cellular level was investigated on fibroblasts of various organs and bone marrow cells in terms of their functional properties. The level of fibroblasts adhesion of all organs studied, as well as the migration ability of fibroblasts decrease, and the level of apoptosis of both cell types increases with increasing concentration and duration of Cd2+. The cells apoptosis also increases with increasing dose and time of exposure to the body of animals. In this case, the degree of apoptosis under constant conditions has distinct organ specificity. The most apoptotic responsive to both doses of cadmium were kidney fibroblasts, and the least sensitive were fibroblasts of the skin.
Bone marrow cells were investigated in vitro, cultivating them for 30 days in the presence of Cd2+ at concentrations of 0.1 and 1.0 μM/l. The influence of Сd2+ on these cells was qualitatively similar to its effect on fibroblasts. The level of adhesion decreased, and apoptosis – increased with increasing both concentration and time of cultivation of bone marrow cells. Indicators of DNA destruction in cells by the action of cadmium – the number of micronuclei, the degree of DNA fragmentation and its single-stranded DNA part – increase with increasing concentration and time of action of Cd2+.
