[Lipid peroxidation in cardiac mitochondrial fraction of rats exposed to different supplementation with polyunsaturated fatty acids].

The effect of diet supplementation with polyunsaturated fatty acids (PUFAs) used at different ratios of w-6/w-3 was studied on the content of primary (diene conjugates, DC; triene conjugates, TC), secondary (ketodienes, CD; coupled trienes, CT; TBA-active products) and terminal (Schiff bases) lipid peroxidation products (LPO) and generation of superoxide anion-radical in rat heart mitochondrial fraction. It was shown that diet supplementation with high doses of w-6 or w-3 PUFAs increased the content of primary, secondary and terminal LPO in rat heart mitochondrial fraction. Llipid peroxidation was accompanied by the intensification of superoxide anion-radical generation in rat heart mitochondrial fraction. During diet consumption with the PUFAs leading factor affecting the intensity of lipoperoxidation in rat heart mitochondria is fatty acid composition, rather than the level of their saturation.

Hepatotoxicity of bisphenol A under conditions of differential supplementation with retinoids.

Classical xenoestrogenic in vivo effects of bisphenol A (2,2-bis(4-hydroxyphenyl)propane, BPA) are well-described in the literature, however the molecular mechanisms of BPA-induced hepatotoxicity are not fully characterized. The work is aimed to assess biochemical markers of BPA induced hepatotoxicity under conditions of differential supplementation with retinoids. We demonstrate that the absence of hepatic retinyl esters as the main form of vitamin A storage provides for a resistance to BPA induced liver damage. Retinoid supplementation increases the hepatotoxic effects of bisphenol A, evidenced in higher indexes of oxidative damage of lipids, proteins and non-protein thiol groups as well as increase of serum alanine aminotransferase activity and myeloperoxidase activity in liver parenchyma. The absence of hepatotoxicity signs when hepatic retinoid stores are depleted and their presence during normal or excessive retinoid supplementation suggest that hepatic retinoid availability is one of the factors determining the hepatotoxicity of bisphenol A.

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

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.

HEPATOPROTECTIVE ACTIVITY OF EXOGENOUS RNA.

Hepatoprotective activity of Nuclex, a pharmaceutical composed of low-molecular yeast RNA, was investigated during acute and chronic thioacetamide-induced hepatotoxicity. It is demonstrated, that Nuclex administration at a dose of 200 mg/kg during acute and chronic liver injury produces hepatoprotective effect, which is associated with decrease in liver parenchyma lesions and in its inflammatory infiltration. Nuclex application attenuates thioacetamide-induced free radical damage of hepatic biopolymers, expressed in the reduction of TBA-reactive products, carbonyl derivatives, and recovery of protein thiol groups and reduced glutathione levels.

[Activity of enzymatic detoxification systems in the mice liver under conditions of different retinoid provision].

The activity of cellular components of liver detoxification system was studied under the conditions of the absence of vitamin A stores. It is shown that a decrease of p-hydroxylase and N-demethylase activity of cytochrome P-450 simultaneously with a decrease of glutathione-S-transferase activity takes place in the liver microsomal fraction of vitamin A-deficient animals. At the same time the absence of retinoid stores in knock-out animals influences the decrease of only p-hydroxylase activity of cytochrome P-450 system. The increase in glutathione-S-transferase activity is observed in the liver postmicrosomal fraction in mice, kept on vitamin A-deficient diet, while its parametres in knock-out group animals were not statistically different compared to the control.

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

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.

[Peculiarities of fractional composition of serum glycoproteins in Guerin's carcinoma development under condition of different vitamin A provision].

The most substantial change in the ratio between glycoprotein fractions distributing in the blood serum of rat under conditions of different vitamin A provision (0.50-0.70 micromol/L) are observed; they are characteristic of gamma-globulin, haptoglobin and alpha 1-acid glycoprotein; the intensity of colouring of their bars decreases on serum electrophoregrammes. At the same time, the decline of intensity of bar coloration of ceruloplasmin fraction takes place under the conditions of middle vitamin A deficiency (0.35-0.50 micromol/L) while that of transferrin takes place at marginal A-deficient state (< 0.35 micromol/L). In latent and logarithmic periods of Guerin's carcinoma growth, regardless of conditions of different vitamin A provision, the intensity of bars colouring, on electrophoregrammes, which correspond to immunoglobulin, haptoglobin, ceruloplasmin alpha2-Macroglobulin, alpha 1-acid glycoprotein and alpha1-antytrypsyn, increases. In a stationary period of tumour growth a decrease of coloration intensity of gamma- and alpha2-globulin fractions is observed.

[Xanthine oxidase activity in the rat liver tissue in the process of oncogenesis].

The work is dedicated to the investigation of xanthine oxidase activity in liver homogenate of rats with tumour at different stages of Guerin carcinoma oncogenesis on the preliminary low-dose irradiation background. Special attention is paid to studying enzyme oxidase form activity, the level of its reactive oxygen species generation and content of thiol groups in protein fraction, which possesses xanthine oxidase activity. The period of Guerin carcinoma active growth is characterized by the increase of total xanthine oxidase activity in the liver. It was found that oxidase activity and the level of O2* generation increase in the preliminary irradiated organism in the period of Guerin carcinoma active growth, as a result of enzyme SH-groups oxidation. At the terminal stages of oncogenesis the decrease of xanthine oxidase activity is accompanied by degradation of the molecule protein part.

A possible mechanism of antitumor activity of 5(5',6'benzocoumaroyl-3')-methylaminouracil in vivo.

AIM: To analyze possible mechanisms of anticancer activity of hydrobromide 5-(5',6'-benzocoumaroyl-3')-methylaminouracil (BCU) in vivo. METHODS: BCU was administered at the dose of 6 mg/kg for seven days to rats bearing Guerin carcinoma (Gc). Interaction of BCU with DNA isolated from Gc cells was analyzed by electrophoresis and spectrophotometry. RESULTS: It has been shown that BCU administration resulted in chromatin condensation, nuclei picnosis, increase of the DNase activity and the appearance of high-molecular DNA fragments in Gc cells. CONCLUSION: BCU is shown to be able to interact directly with DNA molecules with the formation of stable complexes.

[Effect of liposomal antitumor preparation 5-(5',6'-benzocoumarin-3')-methylaminouracil hydrobromide on cytochrome P-450 in the microsomal liver fraction of tumor bearing rats].

Cytochrome P-450 thermal inactivation rate, and content of protein sulfhydryl groups and cytochrome P-450 in the microsomal liver fraction of rats at different stages of Huerin's carcinoma growth were investigated. Liposomal form of BCU administration on the background of preliminary (for 2 hours) administration of phosphatidylcholine liposomes suspension was performed. The low level of cytochrome P-450, protein SH-groups in microsomal liver fraction and increase of the rate of transition of microsomal cytochrome P-450 in P-420 was shown in the dynamics of Huerin's carcinoma growth in an organism. Low microsomal cytochrome P-450 distraction was shown in the rat liver under conditions of antitumor liposomal preparation BCU injection on the 21st day after the transplantation of Huerin's carcinoma. At the same time nonliposomal BCU caused the opposite effect. The preliminary administration of phosphatidylcholine liposomes favours the approach of the investigated parameters to the control values on the terminal stages of tumour growth.

[Extracellular DNA fragments and DNAse activity in blood serum of rats with transplantated Guerin's carcinoma after multiple exposures to low doses of X-irradiation]. / Pozaklitynni frahmenty DNA ta DNA-ase aktyvnist' syrovatky krovi shchuriv iz transplantovanoiu kartsynomoiu Herena na foni bahatorazovoho renthenivs'koho oprominennia nyz'kymy dozamy.

The fraction composition of extracellular free DNA (cfDNA) and activity of serum DNAses in blood of rats with the tumor transplantated against a background of the low-dose X-irradiation were investigated. Heterogeneous fragments of cfDNA and high level of DNAse activity were revealed in the serum of irradiated rats. The definite sizes of high-molecular homogenous fraction of cfDNA, which is observed in the serum of irradiated and unirradiated rats with tumor, and its presence from the first stages of tumor growth independent of serum DNAses activity show, that the emergence of this fraction is not accidental. Previous fractionated irradiation makes influence on the investigation data only on the primary stages of tumor growth.