Comparative morphological and biochemical characteristics of the toxic effects of doxorubicin and nanosomal PLGA-doxorubicin form in the experimental glioblastoma treatment

Abstract

Introduction. Doxorubicin (Dox) in the composition of poly(lactic-co-glycolic acid, 50:50) (PLGA) – nanoparticles has high antitumor efficacy in rats with glioblastoma 101.8. However, the toxic effect of Dox-PLGA is not well understood. The aim of the study was morphological and biochemical evaluation of the hepatotoxic and cardiotoxic effects of doxorubicin and Dox-PLGA in the glioblastoma 101.8 treat-ment in Wistar rats. Materials and methods. The study was performed on 24 male Wistar rats with glioblastoma: 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 the 14th day of the experiment, morphological changes in the myocardium and liver were examined. Hematological and biochemical blood tests were performed. Results.When treating rats with experimental glioblastoma 101.8, Dox-PLGA in comparison with doxorubicin has less pronounced cardiotoxic and hepatotoxic effects according to the morphological, hematological and biochemical tests. Inflammatory changes in the myocardium of the animals treated with Dox-PLGA were less pronounced and widespread than the ones treated with doxorubicin. The activities of total and cardiac creatine phosphokinase (CPK) isoforms and AST were statistically significantly lower in Dox-PLGA group than in animals with glioblastoma without treatment and receiving doxorubicin. The hepatotoxic 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 the reference values. Conclusion. Compared with doxorubicin, the nanosomal form of Dox-PLGA in the experimental glioblas-toma 101.8 treatment has less pronounced cardio- and hepatotoxic effects. Keywords: rat glioblastoma 101.8, doxorubicin, PLGA-nanoparticles, toxic effect, liver, myocardium, morphology, biochemistry