CHARACTERISTIC OF OXIDATIVE STRESS OF ERYTHROCYTUS OF TUMOR-BEARING RATS FOR THE INTRODUCTION OF CLINICAL COMPOSITION OF RENIUM(III) WITH BIOLOGICALLY ACTIVE LIGANDS

Shamelashvili K. L., Shatorna V. F., Grabovska O. І., Shtemenco N. I.

CLINICAL AND EXPERIMENTAL MEDICINE

Scentific article

It is known that the development of the tumor is accompanied by a change in the oxidative-reducing equilibrium with the participation of active forms of oxygen, by the so-called “radical burst”, that leads to the activation of lipid peroxidation (LPO) and to the destruction of the membrane structures of the body. In our previous studies, it has been shown that the cluster Rhenium(III) compounds contain an unique quadruple bond, have anti-carcinogenic activity and reduce the intensity of oxidative stress during carcinogenesis. Recently, our colleagues chemists have synthesized new compounds – a number of cis-dicarbocylates with adamanthyl, ferulate and indolyl ligands, which are the constitutents of many natural and synthetic biologically active substances that we called “biologically active ligands”. Among the compounds studied, the compounds with adamanthyl acid derivatives occupied a separate position, since their administration to tumor rats led to virtually complete inhibition of tumors and support for protein-synthesizing liver function. Actual studies of antioxidant properties of cluster Rhenium(III) compounds with biologically active ligands in erythrocytes are in time, as such studies are being carried out for the first time. The aim of this research was to investigate the effects of Rhenium cluster compounds with adamanthyl ligands in nano-liposomal forms, separately and in combination with cisplatin (Rhenium-Platinum system), on the intensity of lipid peroxidation, erythrocyte integrity and activity of antioxidant enzymes in red blood cells following administration to rats with tumor carcinoma of Guerink. Objects and methods of research. Experiments were performed on the Wistar line rats. 14 animal groups were used. In this work, Rhenium(III) compounds were studied with adamanthyl ligands and cisplatin. The introduction of drugs by 3 methods in nanoliposomal forms to Guerink carcinoma-bearing rats was performed. The activity of superoxide dismutase and catalase, concentration of TBA-active products in erythrocytes and erythrocytic integrity were determined. Research results and discussion. A decrease in the content of TBC-active products was found for the administration of all experimental compounds to rat tumors, regardless of the method of administration to the 6-fold level in comparison to the groups of tumor-bearing rats. The introduction of Re AcAd, regardless of the method, was found to be the most effective in suppressing the intensity of the LPO (5 times compared with the group of rat-tumor carriers) than other experimental compounds. Also, for this group, an increase in the activity of SOD (up to 3 times) and the activity of KAT (on 20%) of erythrocytes for introductions in different ways in comparison with the control was found. The introduction of Rhenium(III) cluster compounds with adamantyl ligands, along with inhibition of tumor growth and activation of SOD, leads to an increase in KAT activity by 13-25% compared with control. Conclusions. Consequently, Rhеnium(III) compounds with adamanthyl ligands did not differ from Rhеnium(III) compounds with alkyl ligands in terms of the ability to decrease the activity of LPO, maintain the integrity of red blood cells, and increase the activity of SOD, but, unlike alkyl dicarboxylates, these substances promoted the activation of CAT in tumor growth erythrocites. Rhenium(III) carboxylates with trans-configuration has been less effective than cis-dicarboxylates. These data may be partially explained by the different direct interaction between cis- and trans- dicarboxylates and proteins that was confirmed by our recently obtained data. Prospects for further research. The further study of the properties of cluster Rhenium(III) compounds and the Rhenium-Platinum systems is promising for the development of new antitumor compounds that would not only suppress tumor growth but also possess antioxidant properties to overcome oxidative stress.

Guerink carcinoma, lipid peroxidation, catalase, superoxide dismutase, cluster Rhenium(III) compounds, erythrocytes integrity

1. Voronkova YS, Babiy SO, Ivans’ka LV, Shtemenko OV, Shtemenko NI. Antyoksydantni vlastyvosti klasternykh spoluk reniyu ta yikh vplyv na erytropoez shchuriv iz kartsynomoyu Herena. Ukr. Biochem. 2015;87(1):45-54. [in Ukrainian].
2. Shamelashvili KL, Shtemenko NI, Leus ІV, Babiy SO, Shtemenko OV. Changes in oxidative stress intensity in blood of tumor-bearing rats following different modes of administration of rhenium-platinum system. Ukrainian Biochemical Journal. 2016;88(4):29-39.
3. Shtemenko OV, Shtemenko NI. Rhenium–Platinum antitumor systems. Ukr. Biochem. J. 2017;89(2):5-30.
4. Bashri G, Prasad SM. Exogenous IAA differentially affects growth, oxidative stress and antioxidants system in Cd stressed Trigonella foenumgraecum L. seedlings: Toxicity alleviation by up-regulation of ascorbate-glutathione cycle. Ecotoxicol Environ Saf. 2016;132:329-38.
5. Ivchuk VV, Polishko TM, Sorochan OO, Shtemenko NI. Stan pechinky shchuriv pry rozvytku kartsyonnykh hereniv ta halʹmuvannya yiyi rostu spolukamy reniyu. Medichna khimiya. 2009;11(3):60-4. [in Ukrainian].
6. Klenina IA, Horila MV, Polishko TM, Shtemenko NI. Vplyv klasternykh spoluk reniyu ta protypukhlynnoyi systemy reniyu-platyny na bilky plazmy krovi. Medychna khimiya. 2011;13(1):63-8. [in Ukrainian].
7. Velychko OV, Golichenko OA, Neikovskyi SI, Shtemenko OV. Syntez tsys-tetrakhlorody-μ-karboksylata dyreni³u (III) z 3-atsetilamino-1adamantankarbonovoiu kyslotoiu. Visnyk Odeskogo Natsionalnogo Universytetu. Khimiya. 2012;17(3):5-12. [in Ukrainian].
8. Grabovska OІ, Kyrychenko SV, Shtemenko NI. Intensyvnistʹ okyslyuvalʹnoho stresu krovi shchuriv za rozvytok kartsynomy Herena ta vvedennya tsysplatynu. Medychna khimiya. 2014;2:42-6. [in Ukrainian].
9. Leus I, Shamelashvili K, Skorik O, Tretiyak C, Golichenko O, Shtemenko O, ta in. Antioksidantnaya i protivoopukholevaya aktivnost’ dikarboksilatov direniya u zhivotnykh s kartsinomoy gerena. Ukr. Biochem. J. 2012;84(3):72-81. [in Russian].
10. Shtemenko N, Pirozhkova-Patalakh I, Shtemenko A, Golichenko A. Izucheniye vliyaniya kompleksov reniya s organicheskimi ligandami na kislotnuyu rezistentnost’ eritrotsitov cheloveka. Ukr Biochem J. 2000;72(3):77-81. [in Russian].
11. Pirozhkova-Patalah I, Shtemenko N. Influence of cis-[Re2GABA2Cl4]Cl2 on the antioxidant defence system parameters of normal human blood. Biochemistry (Mosc). 2001;66(7):721-4.
12. Velychko OV, Shtemenko NI, Shamelashvili KL, Shtemenko OV. Katalazna aktyvnistʹ deyakykh klasternykh spoluchenʹ dorinnya (III). Voprosy khimiyi ta khimichnykh tekhnolohiy. 2017;3(112):4-9. [in Ukrainian].
13. Shtemenko NI, Babiy SA, Chifotides HT. Synthesis, X-ray structure, interactions with DNA, remarkable in vivo tumor growth suppression and nephroprotective activity of cis-tetrachloro-dipivalato dirhenium(III). J Inorg Biochem. 2013;129:127-34.
14. Leus I, Klenina I, Zablotska K, Golichenko O, Shtemenko O, Shtemenko N. Vzayemodiya syrovatkovoho alʹbuminu z klasternymy spolukamy reniyu tsys- i trans-konfihuratsiyi. Biopolymers&Cells. 2011;27(6):465-71. [in Ukrainian]. 

«Bulletin of problems biology and medicine» Issue 4 Part 2 (147), 2018 year, 197-200 pages, index UDK 46.719:54.024:577.151:616-006.69

10.29254/2077-4214-2018-4-2-147-197-200