Tag Archives: doxorubicin

Biochemical indicators of hepatotoxicity in blood serum of rats under the effect of novel 4-thiazolidinone derivatives and doxorubicin and their complexes with polyethyleneglycol-containing nanoscale polymeric carrier

L. I. Kоbylinska1, D. Ya. Havrylyuk1, А. О. Ryabtseva2, N. E. Mitina2,
О. S. Zаichenko2, R. B. Lesyk1, B. S. Zіmenkovsky1, R. S. Stoika3

1Danylo Halytsky Lviv National Medical University, Ukraine;
e-mail: lesya8@gmail.com;
2Lviv Polytechnic National University, Ukraine;
3Іnstitute of Cell Biology, National Academy of Sciences of Ukraine, Lviv

The aim of this study was to compare the effect of new synthetic 4-tiazolidinone derivatives (compounds 3882, 3288 and 3833) and doxorubicin (positive control) in free form and in their complexes with synthetic polyethyleneglycol-containing nanoscale polymeric carrier on the biochemical indicators of hepatotoxicity in blood serum of rats. The activity of enzymes considered as the markers of hepatotoxicity, as well as the concentration of total protein, urea and creatinine were measured in blood serum of rats. It was found that after injection of investigated compounds the activities of alanine aminotransferase, alkaline phosphatase and α-amylase increased in comparison to control. Doxorubicin injection was accompanied by 4-fold increase in the activity of γ-glutamyltransferase, and injection of compound 3833 led to 2.5-fold elevation of the activity of this enzyme. Complexation of these аntineoplastic derivatives with a synthetic nanocarrier lowered the activity of the investigated enzymes substantially if compared to the effect of these compounds in free form. The most evident decrease was measured for α-amylase, γ-glutamyltransferase and lactate dehydrogenase activities. The normalization of concentrations of total protein, urea and creatinine in blood serum of rats treated with complexes of the studied compounds with a polymeric carrier comparing with their introduction in free form was also detected. Thus, the immobilization by novel polymeric carrier of anticancer drugs possessing high general toxicity in the treated organism mitigates their toxic effect, which is evident as normalization of specific biochemical indicators of the hepatodestructive effects of the anticancer drugs.

Metalloproteins during development of Walker-256 carcinosarcoma resistant phenotype

V. F. Chekhun, Yu. V. Lozovska, A. P. Burlaka, I. I. Ganusevich,
Yu. V. Shvets, N. Yu. Lukianova, I. M. Todor, D. V. Demash,
A. A. Pavlova, L. A. Naleskina

R. E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology,
National Academy of Sciences of Ukraine, Kyiv;
e-mial: Lozovskaya.2012@mail.ru

The study was focused on the detection of changes in serum and tumor metal-containing proteins in animals during development of doxorubicin-resistant phenotype in malignant cells after 12 courses of chemotherapy. We found that on every stage of resistance development there was a significant increase in content of ferritin and transferrin proteins (which take part in iron traffick and storage) in Walker-256 carcinosarcoma tissue. We observed decreased serum ferritin levels at the beginning stage of the resistance development and significant elevation of this protein levels in the cases with fully developed resistance phenotype. Transferrin content showed changes opposite to that of ferritin. During the development of resistance phenotype the tumor tissue also exhibited increased ‘free iron’ concentration that putatively correlate with elevation of ROS generation and levels of MMP-2 and MMP-9 active forms. The tumor non-protein  thiol content increases gradually as well. The serum of animals with early stages of resistance phenotype development showed high ceruloplasmin activity and its significant reduction after loss of tumor sensitivity to doxorubicin. Therefore, the development of resistance phenotype in Walker-256 carcinosarcoma is accompanied by both the deregulation of metal-containing proteins in serum and tumor tissue and by the changes in activity of antioxidant defense system. Thus, the results of this study allow us to determine the spectrum of metal-containing proteins that are involved in the development of resistant tumor phenotype and that may be targeted for methods for doxorubicin sensitivity correction therapy.

C60 fullerene prevents genotoxic effects of doxorubicin in human lymphocytes in vitro

K. S. Afanasieva1, S. V. Prylutska1, A. V. Lozovik1, K. I. Bogutska1, A. V. Sivolob1,
Yu. I. Prylutskyy1, U. Ritter2, P. Scharff2

1Taras Shevchenko National University of Kyiv, Ukraine;
е-mail: prylut@ukr.net;
2Technical University of Ilmenau, Institute of Chemistry
and Biotechnology, Ilmenau, Germany 

The self-ordering of C60  fullerene, doxorubicin and their mixture precipitated from aqueous solutions was investigated using atomic-force microscopy. The results suggest the complexation between the two compounds. The genotoxicity of doxorubicin in complex with C60  fullerene (С60+Dox) was evaluated in vitro with comet assay using human lymphocytes. The obtained results show that the C60  fullerene prevents the toxic effect of Dox in normal cells and, thus, С60+Dox complex might be proposed for biomedical application.