The State of Energy Metabolism in Rats with Copper Hyperelementosis

The number of kidney disease resulting from prolonged intake of toxic compounds has increased significantly in recent years in our country (ecodetermined nephropathy). The problem of water pollution with ecotoxints, which are essential elements, is not fully considered. The long-term toxicity of metals, are not considered properly. One such metal is copper, which is available in high amounts in surface waters in many regions of Ukraine. The experimental studies have shown that copper can be deposited in the matrix of lysosomes forming complexes with anionic groups and competing with the calcium and magnesium ions for binding to the active sites of proton pump. Copper ions, entering the cell in an excess amounts, lead to various structural and functional impairments. The high toxicity of copper ions on the one hand, and their role in several metabolic processes on the other hand provide significal theoretical and practical importance study the mechanisms of their action on the biological systems. In this regard, the aim of our study was to investigate the distribution of copper and its effect on energetic processes in the cells of the kidneys of rats in case of high copper intake. Experiments were carried out on 40 male Wistar rats. Animals were divided into the following groups: 1) Intact animals who daily received intragastrically 1 ml of distilled water (control group, 20 rats); 2) animals that daily received intragastrically an aqueous solution of copper chloride (II) (a copper content as 1.75 mg / L; 1 ml per 100 g of body weight, 20 rats). After 1 month of the experiment the animals were decapitated. Kidneys were isolated, washed from blood and stored in a freezer (-80° C). The 10% renal tissue homogenate in Tris-HCl was used. The concentration of copper in serum and tissue homogenates was determined by atomic absorption spectrophotometer "Saturn-3M". Subcellular fractions were isolated by differential centrifugation. The activity of pyruvate dehydrogenase, isocitrate dehydrogenase, succinate dehydrogenase in mitochondria, and ATP content in tissue homogenates were determined by the methods described by Eshchenko ND (7.8). The results obtained were statistically processed using the software package «Statistica v. 6.1.478 »and« Origin 6.0 », using Student's t test, Fisher and Mann-Whitney tests. Results were considered accurate at p <0.05. The content of copper in kidney homogenates and in subcellular fractions of kidney cells of rats from the second group was slightly higher than the physiological need. It was shown that the copper is accumulated in the kidney. There is a significant accumulation of copper in mitochondria and cytosol of renal cells, which can lead to energy deficiency. It was found that the elevated copper content in mitochondria lead to reduced activity of mitochondrial enzymes such as pyruvate dehydrogenase, isocitrate dehydrogenase, and succinate dehydrogenase. During the experiment, shown it was that ATP production, was reduced the excretion of uric acid in experimental rats decreased could, which cause the development of dismetabolic nephropathy. The results allow concluding that the copper intake has nephrotoxic effects.