Open AccessComparative morphological and biochemical characteristics of the toxic effects of doxorubicin and nanosomal PLGA-doxorubicin form in the experimental glioblastoma treatment
Author(s) -
V. V. Kudelkina,
A. S. Khalansky,
Olga Makarova,
И. С. Цветков,
А. М. Косырева,
А. И. Алексеева,
Artem Shelkov,
Olga Maksimenko,
V.A. Razzhivina,
Svetlana Gelperina
Publication year - 2021
Publication title -
kliničeskaâ i èksperimentalʹnaâ morfologiâ
Language(s) - English
Resource type - Journals
eISSN - 2686-6749
pISSN - 2226-5988
DOI - 10.31088/cem2021.10.1.58-65
Subject(s) - doxorubicin , pharmacology , plga , glioblastoma , toxicity , medicine , chemistry , chemotherapy , cancer research , biochemistry , in vitro
. Doxorubicin (Dox) in the composition of poly(lactic-co-glycolicacid, 50:50) (PLGA) – nanoparticles has high antitumor efficacy in rats withglioblastoma 101.8. However, the toxic effect of Dox-PLGA is not well understood. Theaim of the study was morphological and biochemical evaluation of the hepatotoxic andcardiotoxic effects of doxorubicin and Dox-PLGA in the glioblastoma 101.8 treat-ment inWistar rats. Materials and methods. The study was performed on 24 male Wistar rats withglioblastoma: no treatment (n=7), treated with doxorubicin (n=9) or Dox-PLGA (n=8)intravenously at a dose of 1.5 mg/kg on days 2, 5 and 8 after tumor implantation. On the14th day of the experiment, morphological changes in the myocardium and liver wereexamined. Hematological and biochemical blood tests were performed. Results.Whentreating rats with experimental glioblastoma 101.8, Dox-PLGA in comparison withdoxorubicin has less pronounced cardiotoxic and hepatotoxic effects according to themorphological, hematological and biochemical tests. Inflammatory changes in themyocardium of the animals treated with Dox-PLGA were less pronounced and widespread thanthe ones treated with doxorubicin. The activities of total and cardiac creatinephosphokinase (CPK) isoforms and AST were statistically significantly lower in Dox-PLGAgroup than in animals with glioblastoma without treatment and receiving doxorubicin. Thehepatotoxic effects of Dox-PLGA were minimal. Unlike animals treated with doxorubicin,they had mild hepatocyte dystrophy. ALT activity in all groups did not differ from thereference values. Conclusion. Compared with doxorubicin, the nanosomal form of Dox-PLGAin the experimental glioblas-toma 101.8 treatment has less pronounced cardio- andhepatotoxic effects. Keywords: rat glioblastoma 101.8, doxorubicin, PLGA-nanoparticles,toxic effect, liver, myocardium, morphology, biochemistry