O. I. Hrabovska¹, K. L. Shamelashvili², O. V. Shtemenko⁴, N. I. Shtemenko^3,4

¹Institute of Gastroenterology of the National Academy of Medical Sciences of Ukraine, Dnipro;
²SI “Dnipropetrovsk Medical Academy of the Ministry of Health of Ukraine”, Dnipro;
³Dnipro University of Technology, Ukraine;
⁴Ukrainian State University of Chemical Technology, Dnipro;
e-mail: n.shtemenko@i.ua

Received: 18 January 2019; Accepted: 18 October 2019

Contemporary investigations of mechanisms of resistance to platinides showed the key role of copper metabolism in cancer patients and proposed possible methods to attenuate the resistance by modulation of copper transporting mechanisms. In this vein, investigation of ceruloplasmin (Cp) levels – the main copper-containing protein in blood, in experiments with tumor-containing animals upon cytostatics administration is topical and has great importance. The concentration of Cp was measured in the serum of tumor-bearing rats with ordinary (T8) and resistant to cisplatin (T8*) Guerin’s carcinoma upon administration of cisplatin and quadruple bonding dirhenium(III) compound dichlorotetra-μ-isobutyratodirhenium(ІІІ) (I) in different medicamental forms. It was shown that development of tumor in T8 group led to increasing of concentration of Cp in 3.7 times and in T8* group – more than in 8 times in comparison to control, confirming the essential role of Cp in the formation of resistance phenomenon. Administration of cisplatin together with I led to effective inhibition of tumor in groups with T8 and T8*, indicating decreased resistance in the group T8*. Greater reduction of Cp levels was observed in the groups with T8* upon administration of the rhenium-plati­num antitumor system, than in groups with T8, that underlines the importance of further investigations of the dirhenium(III) compounds in the resistance to cytostatics cancer models. Some mechanisms concerning the regulation of copper homeostasis and properties of nano-composites are discussed.