Morphological characteristics of nephrotoxicity of doxorubicin and doxorubicin PLGA-nanoparticles

Abstract

Introduction. Doxorubicin is an anticancer chemotherapy drug that has cardiotoxic, hepatotoxic, and nephrotoxic effects. To reduce the toxic effects of doxorubicin, its nanosomal form, PLGA-doxorubicin [Poly(Lactic-co-Glycolic Acid)], has been developed. PLGA is a biodegradable polymer used as a drug delivery system. The nephrotoxic effects of PLGA-doxorubicin have not been studied yet. The aim was to compare the nephrotoxic effects of therapeutic doses of doxorubicin in standard form (Dox) and PLGA-doxorubicin (PLGA-Dox). Materials and methods. Mature male Wistar rats were injected intravenously three times with Dox or PLGA-Dox solution, at a therapeutic dose of 1.75 mg/kg. The animals were sacrificed on days 8 and 21. We carried out morphological, histochemical, and ultrastructural studies of the kidneys. Results. Under the influence of Dox or PLGA-Dox in the kidneys on days 8 and 21 of the experiment, histological and ultrastructural examination revealed dystrophic changes in the proximal tubules with the destruction of the brush border; in the distal tubules and collecting ducts, protein cylinders were located. Dystrophic changes were more pronounced on day 21 than on day 8. During both periods of the experiment, PLGA-Dox caused less pronounced dystrophic changes in the epithelium than Dox that is confirmed by a morphometric assessment of the number of proximal tubules with a destroyed brush border. Conclusion. The nanosomal PLGA-doxorubicin form has a less pronounced nephrotoxic effect than the classical form of doxorubicin. Keywords: nephrotoxic effect, doxorubicin, nanoparticles, PLGA, morphology