WEB-ресурс научно-практических конференций

Kirichok Y.O., PhD Skorik O.D .

Oles Honchar Dnipropetrovsk National University, Ukraine

INFLUENCE OF CIS- AND TRANS-CONFIGURATION OF ALKYL LIGANDS OF CLUSTER RHENIUM COMPOUNDSIN TO ANTIOXIDANT SYSTEM IN THE MODEL OF TUMOR GROWTH

It is shown that the activity of free radical processes and state of antioxidant protection (AOP) in the body significantly change during the formation of tumours. So one of the most important direction is the study of antioxidant defence in carcinogenesis and search for new antitumor compounds with antioxidant properties. Rhenium compounds aren’t used in medical practice, but in recent years, studies have shown that the injections of rhenium compounds in liposomal form were observed stabilization of antioxidant balance, and reduce the intensity of peroxide stress. So, finding the most effective rhenium compounds and optimal route of administration, which would transport connections provided to tumour cells and their maximum biological activity continues.

Aim of the study was to clarify changes in antioxidant organism capacity under antitumor rhenium compounds and cis -platinum influence in a rat model of specific Guerink (T-8) carcinoma.

Materials and methods: Introduction of rhenium compounds adamantancarboxylate ligands and rhenium-platinum system according to a scheme of antioxidant therapy was tested in a rat model of specific Guerink (T-8) carcinoma.

Activities of superoxide dismutase (SOD), the content of ceruloplasmin were measuring.

Results. Influence of the antitumor rhenium-platinum system in the model of tumour growth (Guerin carcinoma) was studied.

The study SOD activity in plasma of rats with Guerin carcinoma with the introduction of compounds of rhenium and rhenium-platinum system are presented in Figure 1.

The process of tumour growth accompanied by redox balance changing with reactive oxygen species (ROS) participation, which neutralizes superoxide dismutase. The blood plasma group of rats with Guerin carcinoma (T8), SOD activity decreased in 44% compared with the control group. This may be due to the fact that the carcinogenesis products of tumour cells enter the blood and thereby inhibit SOD plasma.

Figure 1. SOD activity in rats’ plasma with Guerin carcinoma under influence of rhenium compounds adamantancarboxylate ligand and cis -platinum, SOD units/mg protein. * – Significant differences compared with the group T8, p <0 ,05 , n = 8 .

Introduction of rhenium compounds contributed to increased enzyme activity in groups [Re- cis -Adam] nl – in 43%, [ cPt + Re- cis -Adam 1:4] nl – in 25%, [ cPt + Re-trans-Adam (1:4)] nl – in 60%, compared with a group of T8. The rhenium-platinum system, which compound was studied in the trans- configuration, proved most effective. However, the introduction of individual compounds showed more appropriate use of cis - configuration compounds to stabilize this indicator.

The study of ceruloplasmin content presented in Figure 2.

Figure 2. The ceruloplasmin content in rats’ plasma with Guerin carcinoma under influence of rhenium compounds adamantancarboxylate ligand and cis -platinum, mg / l. * – Significant differences compared with the group T8, p <0 ,05 , n = 8.

Entering the rhenium compounds and rhenium-platinum system caused decrease of ceruloplasmin in 85-45% compared with a group of T8.

The best results shown for the system rhenium-platinum, where the ratio of rhenium compounds and cis -platinum was 1:4.

  Conclusion: Antioxidant properties of rhenium-platinum system in the model of tumour growth, which was to increase SOD activity at 25-60%, normalization of ceruloplasmin , reflecting the mobilization potential of antioxidant system were shown. The most effective for stabilization of all parameters rhenium compound with adamantancarboxylate ligand in trans-configuration was found. However, the mechanism of action requires more detailed study.