Features of the development of experimental nephropathy in rats during the use of doxorubicin

Abstract

BACKGROUND. One of the most frequently reproduced models of NS is doxorubicin (adriamycin) nephropathy in rats. However, the mechanisms of its development remain insufficiently studied, and it is not entirely clear to which form of NS the nephrotoxicity induced by doxorubicin should be attributed.THE AIM. Reproduction of doxorubicin nephropathy in rats in an attempt to morphologically identify the resulting pathology and determine the role of free radical oxidation (FRO) in the development of this model of nephrotoxicity.MATERIALS AND METHODS. Nephropathy was reproduced by a single intravenous administration of doxorubicin to male Wistar rats. In the urine, the content of creatinine, daily proteinuria, and albumin release were determined. Histological examination of the kidneys was performed using a Libra 120 electron microscope (Carl Zeiss, Germany). The total prooxidant activity, total antioxidant activity, the concentration of thiobarbiturate-reactive products, and the activity of antioxidant enzymes were assessed in the blood and kidney.RESULTS. Against the background of a gradual decrease in the glomerular filtration rate, a significant consistent increase in protein excretion was recorded, largely due to an increase in albumin excretion. Electron microscopic examination revealed a decrease in the number of small (foot) processes of podocytes, their fusion, sclerotic lesions of the elements of the capillary glomerulus, thinning of the GBM, sclerosis of the interstitium. There was a sharp activation of blood OPA and an increase in the content of TBRP. At the same time, such fast-responding antioxidant enzymes as CAT and SOD were activated. The blood TAA decreased in parallel with the decrease in GPO activity.CONCLUSION. Intravenous administration of doxorubicin to rats induced the development of toxic kidney damage with signs of NS. A characteristic indicator was the development of PU against the background of a decrease in GFR from day 5 and increased many times by the end of the observation period. The greatest contribution to the development of PU was made by an in-crease in albumin excretion. Morphological examination of the kidneys using electron microscopy made it possible to conclude with a high degree of probability that the developed pathology and FSGS are similar. At the same time, FRO activation was recorded, which was expressed in a sig-nificant pro-oxidant effect and a significant decrease in the antioxidant activity of the blood.