Open AccessMorphological characteristics of nephrotoxicity of doxorubicin and doxorubicin PLGA-nanoparticles
Author(s) -
И. С. Цветков,
Natalia Zolotova,
А. М. Косырева,
Д. Ш. Джалилова,
V. V. Kudelkina,
Valery P. Chernikov,
В А Мхитаров,
Л. П. Михайлова,
Н. И. Соболева,
V.A. Razzhivina,
M.T. Dobrynina,
Svetlana Gelperina,
Olga Makarova
Publication year - 2021
Publication title -
kliničeskaâ i èksperimentalʹnaâ morfologiâ
Language(s) - English
Resource type - Journals
eISSN - 2686-6749
pISSN - 2226-5988
DOI - 10.31088/cem2021.10.s4.77-86
Subject(s) - doxorubicin , nephrotoxicity , plga , pharmacology , chemistry , medicine , chemotherapy , pathology , toxicity , biochemistry , in vitro
. 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