Showing papers in "Ukraïns'kyĭ biokhimichnyĭ zhurnal in 1999"

Oxidative stress in patients with multiple sclerosis.

Abstract: It is well known that brain and nervous system cells are prone to oxidative damage because of their relatively low content of antioxidants, especially enzymatic ones, and of the high levels of both membrane polyunsaturated fatty acids (PUFA) and iron easily released from injured cells. We have investigated the oxidative stress in the blood (plasma, erythrocytes and lymphocytes) of 28 patients affected with multiple sclerosis (MS) and of 30 healthy age matched controls, by performing a multiparameter analysis of non-enzymatic and enzymatic antioxidants--Vitamin E (Vit. E), ubiquinone (UBI), reduced and oxidized glutathione (GSH, GS-SG), superoxide dismutase (SOD), glutathione peroxidase (GPX), catalase (CAT) and fatty acid patterns of phospholipids (PL-FA). PL-FA and Vit. E were assayed by GC-MS; UBI and GSH/GS-SG by HPLC; SOD, GPX and CAT by spectrophotometry. In comparison to controls, patients with MS showed significantly reduced levels of plasma UBI (0.21 +/- 0.10 vs. 0.78 +/- 0.08 mg/ml, p < 0.001), plasma Vit. E (7.4 +/- 2.1 vs. 11.4 +/- 1.8 mg/ml, p < 0.01), lymphocyte UBI (8.1 +/- 4.0 vs. 30.3 +/- 7.2 ng/ml blood, p < 0.001) and erythrocyte GPX (22.6 +/- 5.7 vs. 36.3 +/- 6.4 U/g Hb, p < 0.001). This blood antioxidant deficiency was associated with plasma levels of PL-PUFA--especially C20:3 n-6 and C20:4 n-6--significantly higher than controls. In conclusion, the blood of patients with MS shows the signs of a significant oxidative stress. The possibility of counteracting it by antioxidant administration plus an appropriate diet, might represent a promising way of inhibiting the progression of the disease. Antioxidant supplements should include not only GSH repleting agents, but also Vit. E, ubiquinol, and selenium.

Units of enzyme activity

Abstract: Units of enzymes activity, recommended by the Nomenclature Committee on enzymes of the International Union of Biochemistry are described the unit E (U), introduced in 1961 and its derivatives: specific activity, molecular (molar) activity, enzyme catalytic centre activity, enzyme solution concentration; the unit catal, introduced in 1972 and its derivatives Information presented is essential to ensure correct expression of enzyme activity

Parameters of peroxidation and proteolysis in the organism of the liquidators of Chernobyl accident consequences.

Abstract: The specificity of lung irradiation caused by ionizing radiation is influence on mucous membranes of respiratory ways, alveolar epithelium and capillaries of a small circle of the blood circulation. Under diseases of bronchus-lung system the lipid peroxidation (LPO) processes activation is observed. The radiating influence strengthening effect. In results in imbalance aggravation in system "LPO-antioxidants", and long expressing of LPO intensification is the important mechanism of the inflammation chronization. The sharp increase of proteolytic activity and inhibitor activity decrease is found out in the patients-liquidators. Noticed imbalance results in the further change of permeability of membranes and correlates with an index of endoscopy inflammation changes and index of irreversible changes in lung tissue. Thus, the direct connection between LPO intensity and imbalance degree of proteinase-inhibitor system of blood at the patients with chronic bronchitic taking part in Chernobyl accident liquidation is revealed.

Development of the myoglobin sensor based on the surface plasmon resonance.

Abstract: Bioaffinic sensor based on the surface plasmon resonance (SPR) with golden layer as a transducer was developed. This sensor was applied for control of antigen-antibodies (Ag-Ab) interactions. For modification of transducer surface the spontaneously organized molecular assemblies of two types of mercaptan were formed. It was shown that the created bioaffinic sensor allowed to detect minimal concentration of antibodies, about 1 ng/ml, to the human heart myoglobin, which preliminary was immobilized on the sensitive surface. The particularities of the dynamics of protein interaction were observed. Duration of incubation with the biospecific component was no more than 5 minutes. After rupturing of specific binding it was possible to obtain initial signal again during 7-9 cycles.

[Antioxidant effect of 20-hydroxyecdysone in a model system].

Abstract: Changes in the level of lipid free-radical oxidation in mitochondrial fraction at the presence of 20-hydroxyecdysone in 1, 2, 4, 6, 8 microM concentration with the help of a chemiluminescence (ChL) method were investigated in vitro. Statistically authentic reduction of ChL kinetic parameters--I(s) and tg alpha, at 20-hydroxyecdysone presence in concentration of 2 microM was found. 20-hydroxyecdysone administration in concentration 4 microM and more leads to the statistically authentic change of all four ChL parameters. The antioxidizing effect of 20-hydroxyecdysone was compared with action of such antioxidant as a hydroquinone. The higher activity of 20-hydroxyecdysone as an antioxidant in comparison with the hydroquinone was shown. For changes of all four measured kinetic parameters of ChL, concentration of the hydroquinone as much 2-fold than for 20-hydroxyecdysone is necessary. On the basis of our researches in the model system a conclusion was made that 20-hydroxyecdysone has an antioxidizing action on lipid free radical oxidation in mitochondrial fraction in dependents on concentration. 20-Hydroxyecdysone has antioxidizing properties directly, in these conditions in vitro, when its metabolites formation does not occur yet.

[Distribution of N-([1-14C]-palmitoyl)ethanolamine in rat tissues].

Abstract: N-([1-14C]-palmitoyl)-ethanolamine distribution was studied in the rat tissues. The following sequence of the label inclusion into tissues by the way of decreasing the radio activity: adrenal >> diaphragm > spleen > kidney > testis > lung > liver > heart > brain > plasma > erythrocytes was obtained.

Mechanisms for increasing the activity of polyreactive immunoglobulins in vivo

Abstract: The mechanisms of increasing of polyreactive immunoglobulin (PRIG) activity in vivo are suggested. It was shown that at some conditions, which can be observed in organism in sites of inflammation, activity of serum PRIG could be enhance considerably. This enhancing might be induced either by reactive oxygen species, mainly by hydroxyl radicals, or by lipases. The increasing of PRIG activity could be not only a result of preexisting PRIG unblocking, but also a result of transformation specific antibodies into PRIG, caused by peroxide degradation or lipolysis of lipids, tightly but noncovalently linked to antibodies, either by hydroxyl radicals or lipase. It was also suggested that most (if not all) specific antibodies consist of not only polypeptide chains, but also some lipids. Deprived of these lipids antibodies loose their specificity and transform into polyreactive immunoglobulins.

[Selenium correction of rat liver status in disturbed antioxidant system, caused by aluminum or cadmium chlorides].

Abstract: Most effective selenium correction of the rats liver antioxidative status disturbance were found after 7-days intoxication by aluminium chloride in the dose 1/5 LD50 than 7-days intoxication cadmium chloride in similar dose.

[Effect of gamma-aminobutyric acid on Mg2+-ATPase of brain microsomes of the fish Abramis brama L].

Abstract: The influence of the GABA on the Mg(2+)-ATPase from microsomal fraction of fish brain (Abramis brama L.) was investigation. Preincubation of the microsomes with different concentration of GABA (10(-8)-10(-4) M) stimulated Mg(2+)-ATPase activity. This effect of neuromediator is sensitive to picrotoxine (10(-4) M). It was established that Mg(2+)-ATPase activity stimulated by anions (Cl > Br > F), inhibited by SCN- and not effected by HCO3-. The influence of the anions on the Mg(2+)-ATPase is liable to be inhibited by picrotoxine. It was supposed that anion-sensitive Mg(2+)-ATPase is associated functionally with GABAa-receptor.

[New systems of coordinates in the study of ligand-receptor interaction].

Abstract: Two new coordinate systems that allow to determine the parameters of ligand-receptor interaction are suggested. These coordinate systems principally differ from the well-known coordinates of Klotz and Scatchard. It was shown that suggested coordinates were simpler and more convenient then coordinates of Klotz and Scatchard and in some cases was more informative. The case when a ligand interacts with two classes of non-identical independent receptors was also considered.

[Inhibitory effect of linoleyl-hydroxamic acid on the oxidation of linoleic acid by 12-lipoxygenase from porcine leukocytes].

Abstract: Linoleic acid oxidation by 12-lipoxygenase from porcine leukocytes has been studied as affected by linoleyl-hydroxamic acid. Linoleyl-hydroxamic acid has been found to be an effective inhibitor of porcine leucocyte 12-lipoxygenase. Aerobic preincubation of 12-lipoxygenase with 0.1-6 microM of linoleyl-hydroxamic acid led to a time- and dose-dependent inhibition of the enzyme. The inhibitor's concentration able to induce a 50% loss of the enzyme activity with and without 15-min preincubation were 3.5 and 0.65 microM, respectively. Experimental results obeyed a kinetic scheme, which supposed 2 extra substrate molecules bounding with the enzyme-substrate complex in the presence of linoleyl-hydroxamic acid.

[Kinetic mechanisms of linoleic acid oxidation by 5-lipoxygenase from Solanum tuberosum L].

Abstract: Linoleic acid oxidation by 5-lipoxygenase from Solanum tuberosum has been studied as affected by sodium dodecylsulfate (Ds-Na). The reaction system consisted of 5-lipoxygenase and mixed micelles of linoleic acid and Lubrol PX. It contained varying amounts of the enzyme effector--Ds-Na. The enzyme showed a pronounced cooperativity, and the reaction was governed by the Hill equation with h = 3.7. On the other side, increasing amounts of Ds-Na added to the system caused a tremendous increase of enzyme activity and simultaneous decline of h, with was proportional to Ds-Na concentration. Ds-Na had dual effect on 5-lipoxygenase--there was an optimal concentration of the compound (0.34 mM Lubrol PX; 0.2 mM LA; 0.13 mM Ds-Na; pH = 6.3) causing the 4-fold highest activation and h = 1.6. The further increase of Ds-Na led to the enzyme inhibition. If Ds-Na was 0.5 mM, h became 1. At this point, each molecule of 5-lipoxygenase bound 3 molecules of Ds-Na and 1 molecule of linoleic acid, thus the total number of occupied binding sites was 4. A kinetic scheme of 5-lipoxygenase reaction has been proposed. It was found that the enzyme's kinetic behaviour could be explaine if assumed an existence of a special noncatalytic binding centre capable of binding several (up to 3) molecules of either substrate, or effector. Such a centre can serve as an anchoring site facilitating the enzyme binding to the surface of lipid aggregates containing insolubilized substrate molecules. Replacing linoleic acid in the binding site, Ds-Na activates the enzyme, possibly due to the much more effective translocation of 5-lipoxygenase to the surface of lipid aggregates. This mechanism can be an universal alternative to the FLAP-type regulation of 5-lipoxygenase activities.

Effect of chronic emotional stress and low dose ethanol on the level of neuronal cell adhesion molecule and glial fibrillary acidic protein in rat brain

Abstract: The effect of chronic emotional stress and ethanol on NCAM and GFAP levels in cerebral cortex, hippocampus, striatum, cerebellum and medulla-ponts was investigated. We report about increase of NCAM and GFAP concentrations in the cerebral cortex and decline of the total protein contents in the investigated brain areas of middle-sleep rats under the stress conditions. Ethanol in the dose of 0.5 g/kg during 7 days evoked opposite changes of NCAM and GFAP concentration and elevation of the total protein level in medulla-pons. In the other brain areas level changes of only one (any) of the two investigated neurospecific proteins were observed. Ethanol injections to the stressed rats normalized the relative weights of adrenals and the level of total protein in the brain areas but didn't normalize the behavioral activity in an "open field" test. Besides, we observed a dramatic increase of GFAP level (over 10 times) in the medulla-pons which may be connected with glioses. These results suggest the specific changes of NCAM and GFAP contents under the chronic emotional stress which don't correlate with changes in the hypophysis-adrenals system.

Structural transitions in polyadenylic acid and hypothesis on biological role of its double-stranded forms.

Abstract: Under various conditions poly(A) exists in different forms such as single-stranded helix, two double-helical forms and others. The formation of double-stranded helices is induced by adenine protonation. Under physiological ionic strengths they are formed at acidic pH, but under the same conditions methylated poly(A) has double-stranded structure at alkaline pH. Since the shift of adenine protonation pKa to alkaline region may be caused not only by chemical modification of poly(A) but also its interaction with proteins, it is quite probable that double oligo(A)-helices are formed in the living cell as well. In this article the hypothesis on possible biological role of poly(A) double-stranded forms has been discussed in details. The models of involvement of double oligo(A)-sequences of RNA in such intracellular processes as termination of mRNA poly(A) tails synthesis and autoregulation of poly(A)-binding protein synthesis are suggested as an example.

[NMR-relaxation of protons in tissue water in evaluating the potential milk-producing ability of cattle].

Abstract: Researching tests on defining the production of the agricultural animals is an actual problem of agricultural biochemistry. In this report, for the first time it is proposed to use the method Nuclear Magnetic Resonance to study the bio-chemical mechanisms of the development of the productivity of the dairy cows. The age-dynamism of NMR-characteristics of the blood and the serum of animals of different genetic types has been examined. Further analysis has been executed on the hormonal regulation of the exchange processes in the organism of the animals. A stable correlation has been established between the time of relaxation of the water-tissue protons and the milk-productivity of the cows. The research has been realised to study the influence of the crossbreeding of ukrainian local races with the Holstein-race on the development of hybrid animals.

[Melanin: structure, biosynthesis, biological functions].

Abstract: Melanins are the group of natural black pigments. The structure of melanin macromolecules is irregular network arising from phenolic precursors in consequence of enzymatic and autooxidation. Melanin is stable polyradical, contain some semiquinone radicals and accumulate the exogene radicals and other active oxygen species, heavy metals, electrophyl toxic compounds. Some this properties determine the antioxidant, antitoxic, antiradiation and antitumour activity of melanins. On the base of natural melanins is possible creation of some effective prophylactic and curative preparations.

Biological role of chromium in humans and animals

Abstract: Chromium (III) is one of the trace elements, which are necessary for human and animal vital activity. It enters the organism from digestive tract and is transported to the tissues, where its accumulation takes place. The deficiency of chromium (III) causes the disturbances in metabolic processes. The primary reaction of organism on chromium (III) deficiency, is the lowered tolerance of glucose, which is the consequence of changes in insulin affinity to its receptors on cells. The considerable quantities of chromium (III) reveal in nucleic acids. It influences on their metabolism, replication and transcription. The ion decreases the content of corticosteroids in plasma and increases the functional activity of immune system of organism.

[Characteristics of antioxidant properties of 20-hydroxyecdysone in low density lipoproteins by kinetic parameters of chemiluminescence].

Abstract: 20-Hydroxyecdysone is capable to terminate the lipid free-radical oxidation in low density lipoprotein in vitro as displayed by the kinetic chemiluminescence parameters. In concentrations interval from 2 x 10(-6) mol/l up to 8 x 10(-6) mol/l it statistically reliably reduces maximum of the first flash intensity of the low density lipoprotein Fe(2+)-initiated chemiluminescence. It testifies about Fe(2+)-initiated lipid peroxide process decomposition in low density lipoprotein slowing down by 20-hydroxyecdysone. In concentration of 20-hydroxyecdysone 8 x 10(-6) mol/l the statistically reliable reduction of angle tangent of an ascending branch of the second flash of low density lipoprotein Fe(2+)-initiated chemiluminescence was found. This is a result of free-radical lipid oxidation rate reduction in the low density lipoprotein at the 20-hydroxyeodysone presence. The equations of the kinetic parameters linear dependences Fe(2+)-initiated chemiluminescence in low density lipoprotein on the concentration of 20-hydroxyeodysone and hydroquinone have been received. The correlation factors in the interval from 0.8980 up to 0.6789 have been calculated. Thus, the assumption has been forwarded that 20-hydroxyeodysone has antioxidizing properties. However, its antioxidizing activity in free radical lipid oxidation of is low density lipoprotein is as less as for hydroquinone.

Determination of antibody affinity using ELISA

Abstract: Some new approaches for the determination of antibody affinity were proposed. It was pointed out that the proposed methods are more simple, convenient, precise, and informative than that of Friguet et al. (1985). The approach that allows determination of two-valence antibodies affinity was also proposed. The example of two monovalent antibodies presented in the examined mixture was considered. It allows to estimate the affinity of both kinds of antibodies as well as to determine their concentration relations in the mixture.

Preparation of fibrin des-AA by thrombin.

Abstract: The active thrombin is formed in the blood stream when the blood coagulation system is activated. It attacks fibrinogen, splits off two fibrinopeptides A and fibrinogen is transformed into des-AA fibrin which is able to polymerize spontaneously forming protofibrils. At high thrombin concentration the enzyme splits off two fibrinopeptides B and des-AA fibrin units are transformed into des-AABB fibrin. These two forms of fibrin are widely used in the biological experiments. However des-AA fibrin is obtained usually from fibrinogen using the snake poisons (such as reptilase). Des-AA fibrin was obtained also by physiological enzyme thrombin, but that des-AA fibrin samples had the contamination of des-AABB fibrin. At the present paper we have described the method of the des-AA fibrin preparation by thrombin without any contamination of des-AABB fibrin.

The problem of determining the affinity of bivalent antibodies using ELISA and its mathematical solution

Abstract: A new approach for the determination of the affinity of monovalent receptors in direct coordinates could be obtained without using Klotz or Scatchard equations. The mathematical solution of the problem of the determination of the affinity of bivalent antibodies by ELISA gives the following relation between absorbance, measured in ELISA. and antigen concentration: omega + square root of omega 2 + omega = liK, where omega = (Ao-Ai)/Ai, Ai is the absorbance, if Ag concentration is equal li; Ao is the absorbance, if Ag concentration is equal zero, K is an equilibrium constant.

Effect of alcohol intoxication and aldehyde dehydrogenase inhibitors on lipid peroxidation in rat liver

Abstract: A single intraperitoneal administration of ethanol (3.5 g/kg) to rats induced a marked increase in lipid peroxidation and a decrease of antioxidative activity in the liver after 1 h when assessed by chemi-luminescence in liver homogenates. The pretreatment with aldehyde dehydrogenase inhibitor, disulfiram (200 mg/kg 24 hr before ethanol), caused a 10-fold elevation of the blood acetaldehyde levels, with no effect on the hepatic lipid peroxidation compared to control. Cyanamide (50 mg/kg, 2 h before the ethanol) increased approximately 100-fold the acetaldehyde levels, however, the changes in lipid peroxidation were not significantly different from that produced by ethanol alone. The present results suggest, that the metabolism of acetaldehyde and not acetaldehyde itself is responsible for the in vivo activation of lipid peroxidation during acute alcohol intoxication. Disulfiram prevents the ethanol-induced lipid peroxidation in the rat liver.

[Radiation-induced changes in the genome of pine seeds, forming under conditions of chronic irradiation in the Chernobyl exclusion zone].

Abstract: Comparative study of long-term existing genome damages in the chronically irradiated pine seeds from different parts of Chernobyl zone have been performed by a pulsed field gel electrophoresis and hydroxyapatite chromatography. Some differences were established for DNA degradation kinetic from protoplasts with various accumulated doses of irradiation. Results obtained could testify the existence of long-living changes in the experimental plants genome.

[Effect of vitamin D3 on free-radical oxidation of lipids in low density lipoproteins in vitamin D deficiency].

Abstract: The lipid free radical oxidation in low density lipoproteins was investigated on D-deficiency model in vivo. The processes of lipid free radical oxidative activation in low density lipoproteins at D-deficiency occurred. The chemiluminescence kinetic parameters: the maximum intensity of the first flash and inclination angle tangent of an ascending branch of the second flash grew at D-deficiency in comparison with control group (p < 0.02 and p < 0.05, respectively). At the same time, the vitamin D3 introduction to the experimental animals diet failed result statistically reliable inclination angle tangent of an ascending branch of the second flash was reduced (p < 0.02). Increase of the products reacting with thiobarbituric acid content in low density lipoproteins in D-deficiency conditions (p < 0.001) was found. Vitamin D3 introduction to the diet reduced quantity of products reacting with thiobarbituric acid in low density lipoproteins (p < 0.01). However, their level remained higher than for the control animals (p < 0.01) as established.

Membrane mechanisms of regulating Ca ion concentration in smooth muscle cells

Abstract: The aim of this review is to summarize some current concepts on the membrane mechanisms of energy-dependent Ca2+ transport in the smooth muscles. The emphasis is placed on the properties and mechanisms of regulation of plasma membrane and endoplasmic reticulum calcium pumps, sarcolemmal sodium/calcium exchanger and mitochondrial Ca2+ transport.

[Effect of alpha-tocopherol and phospholipids with omega-3 fatty acids on membrane properties].

Abstract: As a result of the investigations conducted it was displayed, that alpha-tocopherol and phospholipids including into their composition omega-3-acids, differed in their influencing the composition of heart microsomes membranes lipids. The insufficient quantity of vitamin E in the animals ration was defined as leading to the cardiac microsomes lisophospholipids (lisophosphatidylcholin, lisophospatidylethanolamin), diphosphatidylglycerol increase as well as to the tendency to sphingomyeline and phosphatidylethanolamin decrease. While administrating both alpha-tocopherol and the complex of phospholipids with omega-3-fatty acids, the correction of the phospholipids composition microsomes membranes is observed as tending towards their stabilization, however the marine phospholipids complex is more active than alpha-tocopherol. Administration of phospholipids with omega-3-fatty acids during the period of 30 days provided for the increase of relationship: polyunsaturated fatty acids to saturated fatty acids in the cardiac microsomal membranes, evidencing about increasing the unsaturated cellular membranes. While administrating the phospholipids, into the cardiac microsomes the eicozepentaenic acid was identified, failing to be in the norm, docozahexaenic acid content increased. The results obtained testify, that at the pathology there are changes in the quantitative relationship of membrane phospholipids and fatty acids, being a result of changing the biomembranes permeability as well as their functions disturbances. The adverse effect of E-deficiency to the membrane structure was revealed as capable to be regulated by the marine phospholipid complex, including omega-3-fatty acids.

Effect of low temperature on electron transport in plant mitochondria respiratory chain

Abstract: The etiolated 2.5-day winter wheat sprouts were chilled at 3 degrees C during 24 to 144 hours. After 24 h cooling, shoot intact mitochondria showed a high degree of activation of the alternative oxidase, which was measured as sodium azide and benzohydroxamate sensitivity of the organelles respiration with succinate as a substrate. The role of the alternative oxidase in limiting the level of reactive oxygen species produced in the stressed plant tissues is discussed.

Interaction of thiamine with rat brain synaptosomes

Abstract: Thiamine has been shown to be bound specifically by a synaptosomal plasmatic membrane and transported inside to the nervous ending. Apparent K[symbol: see text] and Km for processes of binding and transport have been determined as equal 2.34 +/- 0.55 MKM and 3.92 +/- 1.3 MKM, respectively. The thiamine uptake by the isolated nervous endings (synaptosomes) at its physiological concentration is reduced in presence of metabolic inhibitors and partially depends on Mg2+ and Ca2+ ions, that can testify about the interrelation between endogenic thiamine phosphorilation and its transport through the membrane. Thiamine binding with synaptosomes is inhibited by ouabain and neurotoxins such as, latrotoxin and most significantly--with veratridin; tetrodotoxin fail to be efficient practically. In the conditions of synaptic membranes depolarisation their ability to bind thiamine is reduced and output of already uptaken with synaptosomes thiamine is observed.

Protein kinases, regulated by calcium and calmodulin: their structure, regulation and cellular functions.

Abstract: In this review we summarize and generalize the recent data on structure, regulation and physiological role of calcium/calmodulin-dependent protein kinases, or CaM kinases. CaM kinases are the family of structurally homologous enzymes, involved into a variety of Ca(2+)-induced cellular reactions through phosphorylation of target proteins. In recent years the quantity of these enzymes has exceeded twenty, mainly due to identification of new isozymic forms of already known CaM kinases. Using crystal structure analysis data, some researchers constructed molecular models of regulation and functioning of CaM kinases. Many reports of recent years are devoted to investigation of functions of CaM kinase isozymes and their role in various cellular processes.

[Status of the rat antioxidant system and correction by medicinal plant preparations during the dynamics of growth of Heren's carcinoma].

Abstract: The work deals with the experimental researches of lipids peroxidation in the rats liver and reduced glutatione and some antioxidant enzymes activity in the same animals blood and liver in dependence on the Heren's carcinoma dynamics as well as in the tumor-carriers ones injected subcutaneously by "NIKA" herbal preparation. As the result of the experiments it was identified, that in the course of the tumor growing there was an increase of the rats liver level of malonic dialdehyde--the final product of the lipids peroxidation, as well as of some antioxidant enzymes activity growth in the blood and liver. In the 21-th day following the tumor implantation the animals-tumor-carriers antioxidant system is exhausted. The tested herbal medicine displays the normalizing and correcting action on the rats organism protective system and provides for the tumor growth slowering.