Relationship of lithogenesis and oxidative damage in experimental nephrolithiasis

Abstract

Introduction: Modern literature indicates that tissue damage in the kidneys is an important factor in the formation of urinary stones. It is recognized that the deposits of calcium salts are capable of inducing tissue reactions in the epithelium of the distal tubules and collecting tubules, particularly activating the process of free radical oxidation. Material and Methods: The morphological study of 60 rat kidneys with experimental oxalate nephrolithiasis was conducted. To identify the calcium deposited, silver impregnation by von Kossas method was used. Using immunohistochemistry, the expression of the severity indices of oxidative damage (malondialdehyde - MDA) and antioxidant defenses (mitochondrial superoxide dismutase - SOD-2) were determined. Results: After 3 weeks of the nephrolithiasis modeling in the epithelium of the collecting tubules, in the interstitium of the medulla substance, in the lumen of collecting tubules numerous calcium deposits were found (mean 21.4±3.40 in the field of view). The average size of the deposits was observed to be 16.510.60 mm. In 10% relatively large microlites (up to 30-35 pm) were found with obturation of the lumen of the collecting tubules. Noted decreased expression (1+) of SOD-2 in epitheliocytes. The weakening expression of the antioxidant enzyme was accompanied by a statistically significant elevation of lipid peroxidation products (2+).With using of a-tocopherol in the experiment, a much smaller intensity of histopathological kidney restructuring was determined. The moderate amount (up to 17.612.39 in the field of view) of calcium compounds were small, averaging 5.4010.28 mm in size. Large compounds of calcium, obturation clearance tubules and collecting tubules, or inlays their epithelium were not detected. Immunohistochemical study of the rat kidney during treatment with a-tocopherol showed moderate (2 i) expression of the SOD-2 in epitheliocytes of the collecting tubules, comparable to the intact group and significantly (12.5%) higher than in animals with an experimental model oxalate nephrolithiasis. The intensity of the expression of MDA was similar to that in the intact group and significantly lower in animals with the experimental oxalate nephrolithiasis. Conclusion: During the simulation of the experimental oxalate nephrolithiasis in the rat kidney, marked morphological signs of oxidative damage activation in the tissues and cells and a weakening of the enzymatic antioxidant defense system, accompanied by an acceleration lithogenesis were noted. The usage of antioxidants has beneficial effects on the renal morphologic reorganization, as it reduces the degree of oxidative damage to the cells and tissues, while it helps to reduce the number and size of the calcium deposits formed