Tag Archives: Guerin’s carcinoma

Free radical oxidation in liver mitochondria of tumor-bearing rats and its correction by essential lipophilic nutrients

O. V. Ketsa, M. M. Marchenko

Fedkovich Chernivtsy National University, Ukraine;
e-mail: o.ketsa@chnu.edu.ua

Received: 21 May 2019; Accepted: 29 November 2019

The role of free radical oxidation in the increase of mitochondrial membranes permeability in organs which are not involved in oncogenesis and the development of the methods for preventing mitochondria dysfunction remain topical problems. In this work, the interconnection of lipid peroxidation (LPO) in liver mitochondrial fraction with the processes of mitochondrial swelling and cytochrome с release to the cytosol under separate and combined administration of ω-3 polyunsaturated fatty acids (PUFAs) and retinol acetate (vitamin A acetate) to rats with transplanted Guerin’s carcinoma was studied.  During the intensive tumor growth (14 days) the increase of superoxide radical generation and the content of primary (triene conjugates, TC), secondary (ketodienes and coupled trienes, CD+CT) and terminal (Schiff bases) lipid peroxidation products­ in the mitochondrial fraction of tumor-bearing rats was detected, which contributed to the mitochondrial swelling and cytochrome с release to the cytosol. Separate administration of ω-3 PUFAs to tumor-bearing rats decreased both free radical processes in mitochondrial fraction and mitochondrial swelling. Separate administration of retinol acetate in a high dose (3000 IU/kg of body weight) intensified free radical processes in the mitochondrial fraction of tumor-bearing rats, while administration of retinol acetate in a physiological dose (30 IU/kg of body weight) did not lead to changes compared to tumor-bearing rats that did not receive the drug. The prooxidant effects of retinoid were partially eliminated in the case of combined administration with ω-3 PUFA.

The concentration of ceruloplasmin in blood of tumor-bearing rats after administration of a dirhenium(III) compound and cisplatin

O. I. Hrabovska1, K. L. Shamelashvili2, O. V. Shtemenko4, N. I. Shtemenko3,4

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.

Biochemical features of cancer cachexia under conditions of different provision with vitamin A

I. O. Shmarakov, N. V. Gnep, M. M. Marchenko

Yuriy Fedkovych Chernivtsi National University, Ukraine;
e-mail: igor.shmarakov@gmail.com

On the model of tumor growth of Guerin’s carcinoma and experimental modeling of vitamin A provision the biochemical characteristics of tumor cachexia in animals with malignant tumors and different vitamin A provision status were studied. It is determined that tumor growth in the body, deprived of vitamin A, is characterized by negative nitrogen balance, decrease of glucose, free fatty acids and ketone bodies level in the blood serum, which indicates the increase of cancer cachexia.

Monooxygenase system in Guerin’s carcinoma of rats under conditions of ω-3 polyunsaturated fatty acids administration

M. M. Marchenko, O. V. Ketsa, I. O. Shmarakov, K. H. Abutnaritsa

Fedkovich Chernovtsy National University, Ukraine;
e-mail: ketsa80@mail.ru

The aim of the study was to determine the variations of function in components of monooxygenase system (MOS) of rat Guerin’s carcinoma  under ω-3 polyunsaturated fatty acids (PUFAs) administration. The activity of Guerin’s carcinoma microsomal NADH-cytochrome b5 reductase, the content and the rate of cytochrome b5 oxidation-reduction, the content and the rate of cytochrome Р450 oxidation-reduction have been investigated in rats with tumor under conditions of ω-3 PUFAs administration. ω-3 PUFAs supplementation before and after transplantation of Guerin’s carcinoma resulted in the increase of NADH-cytochrome b5 reductase activity and decrease of cytochrome b5 level in the Guerin’s carcinoma microsomal fraction in the logarithmic phases of carcinogenesis as compared to the tumor-bearing rats. Increased activity of NADH-cytochrome b5 reductase facilitates higher electron flow in redox-chain of MOS. Under decreased cytochrome b5 levels the electrons are transferred to oxygen, which leads to heightened generation of superoxide (O2•-) in comparison to control. It was shown, that the decrease of cytochrome P450 level in the Guerin’s carcinoma microsomal fraction in the logarithmic phases of oncogenesis under ω-3 PUFAs administration may be associated with its transition into an inactive form – cytochrome P420. This decrease in cytochrome P450 coincides with increased generation of superoxide by MOS oxygenase chain.

Changes in oxidative stress intensity in blood of tumor-bearing rats following different modes of administration of rhenium-platinum system

K. L. Shamelashvili1, N. I. Shtemenko2, І. V. Leus3, S. O. Babiy4, O. V. Shtemenko5

 1SE “Dnipropetrovsk Medical Academy” of Health Ministry of Ukraine;
2Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
3University of Oklahoma, Oklahoma-city, USA;
4Institute of Gastroenterology, National Academy of Medical Sciences
of Ukraine, Dnipropetrovsk;
5Ukrainian State University of Chemical Technology, Dnipropetrovsk;
e-mail: shamelashvili@rambler.ru

Effects of the different modes of administration of dichlorotetra-μ-isobutyratodirhenium(ІІІ) – І – (in water solution, liposomes, nanoliposomes and together with cisplatin – in the rhenium-platinum system) on the intensity of lipid peroxidation (LP) in blood plasma and the activity of the erythrocyte antioxidant enzymes were investigated on the model of tumor growth. A decrease in the concentration of TBA-active substances caused by dirhenium compounds was shown to be independent of the administration mode and the extent of the tumor growth inhibition. I was four-times more effective in inhibition of the LP burst than any known antioxidant. I induced the increasing activity of erythrocyte superoxide dismutase and decreasing activity of catalase. In vitro experiments with native superoxide dismutase, the interaction of І with following activation of the active center of the enzyme was confirmed and the superoxide dismutase activity of І was shown, that may contribute to the enhancement of the enzyme activity in vivo. The cluster rhenium compounds may be promising nontoxic potent antioxidants capable of deactivating superoxide radicals.

Generation of superoxide anion-radical in the liver monooxygenase system of preliminary radiation-exposed tumor-bearing rats

М. М. Marchenko, O. V. Ketsa

Yuriy Fedkovych Chernivtsi National University, Ukraine;
e-mail: ketsa80@mail.ru

Generation of superoxide anion-radical (O2•-) in reductase and oxygenase electron-transport chains in the liver monooxygenase system was investigated in tumor-bearing rats exposed to preliminary irradiation. Preliminary irradiation of rats (before transplantation of Guerin’s carcinoma) resulted in the increased generation of superoxide anion-radical by components of the liver monooxygenase system in the logarithmic phase of oncogenesis­.
It is shown that the increased NADPH-cytochrome P-450 reductase activity is accompanied with the intensification of superoxide anion-radical generation in liver microsomal fraction of preliminary radiation-exposed rats. At the same time the cytochrome P-450 hydroxylase activity in the microsomal fraction of tumor-bearing rats subjected to preliminary irradiation was decreased.