Showing papers in "Ukraïns'kyĭ biokhimichnyĭ zhurnal in 2000"

Transport and metabolism of vitamin A

Abstract: The present paper is a review of up-to-date findings on vitamin A transport from intestines to target-cell and metabolism of this fat-soluble vitamin. The hypotheses of possible enzymes participation in the process of etherification/hydrolysis and oxidation/reduction of vitamin A are discussed. Furthermore, possible roles of cellular retinoid-binding proteins in the process of vitamin A transport and metabolism are reviewed.

Oversynthesis of riboflavin by yeast Pichia guilliermondii in response to oxidative stress.

Abstract: The effect of oxidative stress on riboflavin (vitamin B2) biosynthesis and iron accumulation in flavinogenic yeast P. guilliermondii was investigated. Treatment of P. guilliermondii cells with superoxidgenerating agent methylviologen leads to elevated production of malondialdyhyd (MDA) which reflects the overall cellular oxidation state. Increased iron content in the cells and enhanced productivity of flavinogenesis under these conditions has been shown too. Significant increasing of MDA and riboflavin production by yeast cells under iron deficiency was observed. Riboflavin overproducing P. guilliermondii mutant strains rib80, rib81 and hit, possess high iron transport and synthesize increased quantity of MDA. The role of riboflavin overproduction and activation of iron assimilation in the P. guilliermondii antioxidant defence is discussed.

Effect of the mycotoxin zearalenone on the metabolism of membrane phospholipids of rat lymphocytes

Abstract: The data obtained have shown that a single intravenous administration of 1 ml of mycotoxin zearalenon alcohol solution (15 mg/ml) to rats leads to the formation of pronounced abnormalities in lymphocyte membranes phospholipid (PL) metabolism. These changes are conditioned by activation of phospholipase A2, which catalyses the deacylation of PL-glycerides predominantly phosphatidylcholines with the formation of high concentrations of lysophosphatidylcholines. On the other hand, intensification of deacylation processes of PL, which accompanied by the liberation of high quantities of unsaturated fatty acids leads to the active incorporation of its into the processes of lipids free radical peroxidation with the formation of significant quantities of lipid peroxides. Intraperitoneal administration of 1 ml 10% sol of sodium thiosulfate no later then 1-2 h after zearalenon toxic action leads to the normalization of disorders observed.

ELISA-based method for determining the affinity of bivalent antibodies of two specificities in a mixture.

Abstract: The problem of the evaluation of the affinity for two types of bivalent antibodies in a mixture is considered. It is shown that the binding curve in appropriate coordinates can be used to compose either a system of four equations with four unknowns or a system of two equations with two unknown variables. The numerical solution of these equation systems yields affinity constants for both antibodies and the relationship between concentrations of antibodies studied in the mixture.

[Activity of cytoplasmic proteinases from rat liver in Heren's carcinoma during tumor growth and treatment with medicinal herbs].

Abstract: The dynamics of the acid and neutral proteinases general enzymes activity change in the hepatocytes postnuclear fraction in the rats suffering from the Heren's carcinoma was investigated. It was determined that in the tumor development of the enzyme activity level of both the acid and neutral proteinases increased 2,6-fold. The natural preparation of the herbs (Calendula officinalis L., Echinacea purpurea L., Scorzonera humilis L., Aconitum moldavicum Hacq.) normalizes both the activity of the investigated enzymes and coefficients of the liver weights of the sick animals. The chemical medicinal preparation 5,6-benzcumarine-5-uracil normalizes the activity of the neutral cytoplasmatic proteinases and reduces the level of the proteolytic activity of the acid enzymes in comparison with the control group of the animals as well as increases of the liver weight coefficients.

Deprotonated carboxylic group of amino acids transforms adenine into its rare prototropic tautomers.

Abstract: By UV spectroscopic data for anhydrous DMSO solutions and ab initio HF/6-31G** calculations in vacuum it was shown for the first time that deprotonated amino acid carboxylic group is able to change tautomeric state of a nucleotide base, exactly to convert the N9H ground-state prototropic tautomer of adenine into the N7H and N1H rare ones.

Antioxidant and biological activity of melatonin

Abstract: Neurohormone melatonin controls the circadian rhytmicity of some biological processes, unites the functions of nervous, endocrine and immune systems. Melatonin is a powerful bioantioxidant, capable to be dissolved in water and lipids, runs through membranes and barriers, accumulates in cell nuclei and protects DNA from oxidative stress. Melatonin displays immunomodulating, radioprotective and antitumor activities.

Biologically active substances isolated from Hypericum attenuatum Choisy

Abstract: Four dianthrones, two oxymethylanthraquinones, two reductive forms of anthraquinones and five flavonoids have been isolated from the plant source Hypericum attenuatum Choisy (Guttiferae) firstly investigated for these substances contents. Dianthrones pseudohypericin, protohypericin, protopseudohypericin, oxymethylanthraquinones frangulaemodin, frangulin, reductive anthraquinones emodin anthrone, emodin anthranol, and flavonoids quercetin, quercitrin, isoquercitrin, rutin have been identified for the first time. High hyperoside contents in herb of Hypericum attenuatum is established.

Effect of chitosan on lipid peroxidation in toxic liver injury

Abstract: Lipid peroxidation was intensified by tetrachloromethane in liver. Concentration of lipid peroxidation products was decreased after chitosan injections. It was shown that application of chitosan had a positive effect on the liver of mice intoxicated by tetrachloromethane.

Proteolytic system in lungs upon inhalation exposure to low doses of lead salts

Abstract: Changes in proteinase--antiproteinase activities in lungs as a result of short-term (for 1 week) inhalation of rats with 0.01% (CH3COO)2 Pb have wholly compensative patterns, but it have been found increased cathepsine B activity as a negative prognostic factor. Chronic (for 2 month) toxicant inhalation caused considerable activation of both trypsine and cathepsine B under decreasing alpha 1-antitrypsine and alpha 2-macroglobuline activities. Cathepsine L activity was not affected. Disorders in the proteolysis system were evaluated as desadaptation situation in lung tissue under chronic toxic influence.

[Features of fibronectin-dependent activation of ribosomal protein S6 kinase (S6K1 and S6K2)].

Abstract: Integrin family of adhesion receptors play an important role in organizing the actin cytoskeleton and in signal transduction from the extracellular matrix. The previous studies have shown that exposure of fibroblast cells to extracellular matrix proteins activates ribosomal S6 kinase 1 (S6K1) pathway in a ligand dependent manner. Recently, a new, highly homologous ribosomal S6 kinase, termed S6K2, was identified. It has 70% amino acid identity in the overall sequence with S6K1, and the potential phosphorylation sites of S6K1 are conserved in S6K2. However, the N- and C-terminal domains of S6K2 are quite different from those of S6K1. In this study we have examined dynamics of fibronectin-induced activation of these two kinases, transiently expressed in human HEK 293 cells. Differences between profiles of activation of S6K1 and S6K2 were observed in the early period of fibronectin stimulation. Fibronectin-induced changes in S6K2 activity were closely correlated with phosphorylation at Ser423, which is homologues to Ser 434 of S6K1. Although we didn't observe considerable changes in phosphorylation of S6K1 at Ser434, suggesting potential differences in the regulation of these homologous kinases upon fibronectin stimulation.

[N-acylethanolamine--a new class of natural adrenotropic modulators].

Abstract: N-acyl-ethanolamines (NAE) belong to the new class of naturally occurring biologically active regulators. Anandamide--a well known representative of NAEs--is an agonist of central (CB1) and peripheral (CB2) cannabinoid receptors. Adrenal cortex contains the CB2 receptor. The aim of present work is to investigate the influence of saturated and polyunsaturated NAEs on the corticosteroid synthesis in adrenal gland in vitro. It was shown that the rat adrenal gland is the main target of N-([1-14C]palmitoyl)ethanolamine incorporation. Saturated NAE enhanced the incorporation of [3H]-cholesterol into the aldosterone by 25% (p < 0.06) and corticosterone by 17% (p < 0.05) of rat adrenal slices in vitro. Mixture of polyunsaturated NAEs containing mainly 18:1w9, 18:2w6, 18:3w3, 20:1w9, 22:1w9 increased the labeling of aldosterone by 70% (p < 0.05) and corticosterone by 20% (p < 0.05). Thus, the saturated NAEs as well as polyunsaturated analogs, act by the similar manner on the corticosteroid synthesis. The fact that saturated NAEs possess poor affinity to CB receptors provides us opportunity to suggest the non-receptor mechanism of NAEs adrenotrophic action. Further we used the purified bovine serum albumin to test the binding kinetic of N-([I14C]palmitoyl)ethanolamine with its hydrophobic domains. It was found that NAEs have high affinity to hydrophobic domains of protein with K = 2.5 x 10(8) M-1. This finding could support the idea of the existence of putative allosteric modulation of regulatory protein function. It was concluded that NAEs exert a stimulatory effect on the corticosteroid synthesis in rat adrenal gland in vitro and this action do not mediated trough cannabinoid receptor.

Characteristics of bacterial lipopolysaccharides depending on extraction method

Abstract: Carbohydrate-containing biopolymers have been isolated from Erwinia carotovora subsp. atroseptica 549 by two methods--the aqueous-phenol and with using physiological solution--with addition and without addition of ethylenediaminetetraacetate (EDTA). The biopolymers yield from the cells of bacteria are shown to depend on the extraction method. Lipopolysaccharide-protein complex have been isolated by the sparing method. The purest lipopolysaccharide have been isolated by the aqueousphenol method. The preliminary treatment of cells by EDTA increased the biopolymers output. Carbohydrate containing biopolymers isolated from the cells of bacteria by different methods possess the similar qualitative composition of monosaccharides but they differ in the quantitative content of monosaccharides, spectrum of fatty acids of lipid components as well as in the protein content.

Effect of carnosine on the erythrocyte membrane in normal states and in diabetes

Abstract: Administration of carnosine (beta-alanyl-L-hystidine) at 5 mg/100 g body weight per os was defined as normalising the acid erythrogram parameters in the experiments on rats with streptozotocin-induced diabetes.

Human anti-DNA secretory immunglobulins A possess endonuclease activity and they are able to cause the destruction of nuclear chromatin in vitro.

Abstract: sIgA possessing ability to hydrolyse plasmid DNA to linear forms was purified from human milk by sequential chromatography on protein A-sepharose, DEAE-Fractogel and DNA-cellulose. It was discovered that incubation of sIgA with nuclei of porcine embryo kidney cells permeabilized by Triton X-100 causes formation of electrophoretically mobile forms of nuclear nucleic acids and inhibition of phosphorylation of nuclear proteins. We suppose that sIgA possessing affinity to DNA and endonuclease activity can cause degradation of cell nuclear chromatin.

[Role of xanthine oxidase and xanthine dehydrogenase systems in thymocyte apoptosis, induced by papaverine].

Abstract: It has been established that papaverine as well as other xenobiotics (dexamethasone and nitrosodimethylamine) [figure: see text] provoked the thymocyte death like apoptosis. The increase of the quantity of double-strand, single-strand DNA breaks and low molecular weight fragments of DNA preceded cell death. In papaverine-induced process of thymocyte apoptosis the total activity of xanthine oxidase in thymocytes strongly elevated long before their death, the conversion of xanthine dehydrogenase (D-form) to xanthinoxidase (O-form) and accumulation of O-form in the cultural medium took place. Direct stimulating effect of papaverine on O-form of enzyme in thymocyte lysate was revealed. The used digitonin thymocytes were divided into cytoplasmic and structural component fractions. It was shown that about 80% of total xanthinoxidase activity was concentrated in cytoplasma while only 20% of its activity was found in structural components. More higher ratio of xanthinoxidase/xanthindehydrogenase (XO/XDH) was observed and papaverine-induced changes of these enzyme forms activities were expressed more brightly in the structural components, than in the thymocyte cytoplasma. During the process of developing thymocytes apoptosis caused by papaverine the reaction of lipid peroxidation was intensified. XO-hypoxanthin system displaying prooxidant influence on cells increased the cytotoxic effect of papaverine but the presence of allopurinol or catalase and superoxidedismutase decreased it. Besides, cytotoxic action on thymocytes of allopurinol itself as well as hypoxanthin itself was revealed.

[Immunosensors: sources of origin, achievements and perspectives].

Abstract: The analysis of the recent data in the literature and results of investigations in the field of the development and study of function efficiency of different types of immune sensors, that are performed at the Department of Biochemistry Sensory and Regulatory Systems of the A. V. Palladin Institute of Biochemistry of Ukrainian National Academy of Sciences are presented. Sources of origination and perspectives of the devlopment of biosensors are discussed as well. The paper also gives an overview of main research projects at the Department, mainly in the filed of biosensors. They include development of the scientific bases for the creation of a new generation of chemo- and biosensors for their application in medicine and ecology. Multi-immune, multi-enzyme and combined multi-parametrical sensors can provide express analyses in laboratory and field conditions with the purpose to perform immune chemical diagnostics of diabet, kidney diseases, immune defficiencies, autoimmune, allergic, pre-infarction and pre-tumor states as well as to control total toxicity of the environment and identification of main types of toxic elements in it. The investigations are based on the latest achivements in the field of physics, chemistry, information technology and electronics with the use of different types of planar electrodes, ion sensitive field effect transistors (ISFETs), semiconductor capacitive structures, termistors, optrodes, piezocrystalls and application of such methods and effects as laser correlation spectroscopy, chemiluminescence, fluorescence, surface plasmon resonance, photoluminescence of porous silicon, interferometry, evanescent wave technique, nonemmiting energy transfer and holography.

[AMP-deaminase: regulation and physiological role of the enzyme].

Abstract: AMP-deaminase (AMPD) catalyzes the irreversible hydrolysis of AMP to IMP and ammonia. Being the integral enzyme of purine nucleotide cycle, AMPD participates in deamination of amino acids and their involvement into carbohydrate metabolism. This enzyme competes with 5'-nuclease for AMP it is indirectly involved in regulation of adenosine level. The role of AMPD may be supported also by the correlation between its activity and several neuromuscular and immunologic pathologies. The information on the izoforms, gene expression both in the normal and pathological states is given. Activity of AMPD is regulated by the substrate availability, adenylate pool, GTP, product of catalysed reaction IMP, ++inorganical phosphate, etc. Currently the growing scope of data is displaying the possible role of reversible phosphorylation and binding to cellular elements in regulation of the properties of AMPD under change of physiological state of organism.

Physiologic functions of vitamin D3 and its metabolism in the body in normal states and in some pathologies

Abstract: In the review there are some results of investigations of the laboratory summarized on the mechanisms of vitamin D3 metabolism and its functioning in organism; investigation of infringement of mineral, lipid and protein metabolic processes with vitamin D3 deficiency and with different pathologies and the ways of their regulation as well as the data about some new high-effective forms of vitamin D3 for their implementation in medicine and agriculture.

[Influence of saturated long-chain N-acylethanolamines on lipid composition and heart contractility of isolated rat heart under ischemia-reperfusion].

Abstract: The heart contractility and changes of lipid composition of isolated rat heart (n = 26) under total ischemia and ischemia-reperfusion was studied. The effect of N-stearoyl-ethanolamine under these conditions was investigated. N-stearoyl-ethanolamine leads to remodelling of fatty acyl chain composition of myocardial phospholipids: to drastic fall of polyunsaturated fatty acyl chains (18:2w6, 20:3w6, 20:4w6, 22:5w3, 22:5w6, 22:6w3 and 22:6w6) and enhancement of 18:0. This can be caused by N-stearoyl-ethanolamine-induced suppression of polyunsaturated fatty acids synthesis. Naturally occurring minor lipids--N-acyl phosphatidylethanolamine and its derivative N-acylethanolamine were detected in isolated rat heart under ischemia-reperfusion. It is notable that approximately 12% of total N-acylethanolamines were composed by anandamide. Treatment of N-acyl phosphatidylethanolamine by phospholipase D with subsequent fatty acyl chain analysis demonstrates that fatty acid composition of both N-acyl chains of N-acyl phosphatidylethanolamine and free N-acylethanolamine are similar and their main fatty acyl chains are 16:0, 18:0 and 20:4w6. It was shown that exogenous N-stearoyl-ethanolamine did not alter the levels of endogenous N-acyl phosphatidylethanolamine and N-acylethanolamine, but caused the decrease of lyso-phosphatidylcholine and phosphatidylglycerol levels. The rate of heart contractility and heart relaxation was found to increase during the early period of reperfusion. N-stearoyl-ethanolamine prevents this alteration and exerts a negative inotropic effect. It is concluded that membrane protective properties of N-stearoyl-ethanolamine at least partly depend on its ability to inhibit decrease amount of arachidonic and docosahexaenoic acids, to modulate the fatty acyl chains of cardiac phospholipids and to decrease the level of lyso-phosphatidylcholine.

[Effect of chlorpromazine on the Ca2+-transport system of secretory cell membrane in Chironomus plumosus L. larval salivary glands].

Abstract: Effect of chlorpromasine (specific blocking agent of calmoduline) on Na(+)-Ca(2+)-exchanger functioning, Ca(2+)-pump and potential dependent Ca(2+)-channels in plasmatic membrane of isolated salivary glands in Chironomus plumosus L. larvae was investigated. Addition of chlorpromasine in different concentrations to the incubation medium with physiological Na+ and K+ concentration increased Ca2+ content in the gland tissue and secretion of general protein by gland cells. Chlorpromasine addition to the hyposodium and hyperpotassium mediums decreased Ca2+ content in the gland tissue and protein secretion. We made a conclusion that chlorpromasine, as an inhibitor of calmoduline, blocks Na(+)-Ca(2+)-exchanger and Ca(2+)-pump of plasmatic membrane of secretory cells. Potentialdependent Ca(2+)-channels are also effectively blocked by chlorpromasine but mechanism of this process is unknown. We suppose that Ca(2+)-calmoduline complex forming leads to increase of calcium oscillations amplitude in the cells of the investigated glands and stimulation of secretion.

Fermentative synthesis and hydrolysis of fructans

Abstract: The review of the experimental papers dealing with some aspects of fermentative biosynthesis of fructans with different degrees of polymerization from microorganisms and plants is presented. The role of sucrose 1F-fructosyltransferase and 1,2-beta-fructan 1F-fructosyltransferase in the biosynthesis and hydrolysis of fructans, the influence of different stresses (water, temperature, oxygen and others) on these process are discussed.

Concentration of transferrin iron and transferrin saturation in blood

Abstract: Transferrin iron, transferrin protein concentrations, and transferrin saturation have been determined for the first time in the whole blood. Microsamples were taken from healthy adults and patients with occupational secondary haemochromatosis using quantitative electron spin resonance technique. At elevated transferrin saturation, transferrin saturation values determined in the plasma and serum samples were shown to be less than respective values determined in the whole blood of the same patients. At increased transferrin iron concentration the difference between experimental and reference data sets determined in the blood and plasma was statistically significant in contrast to data sets determined in serum. Therefore, the analysis of the blood microsamples ensured an adequate estimation of transferrin iron concentration, especially at high transferrin saturation. A new index--transferrin iron concentration in the formed blood elements--was introduced. The values of the index were determined in the groups of healthy adults, patients with secondary occupational hemochromatosis and healthy newborns.

[Effect of calmodulin on myometrial cell membrane Ca2+,Mg2+-ATPase activity].

Abstract: The modulatory effects of calcium ions on highly active Na+, K(+)-ATPase from calf brain and pig kidney tissues have been studied. The inhibitory action of Ca2+free on this enzyme depends on the level of ATP (but not AcP). The reduction of pH from 7.4 to 6.0 noticeably increases, but the elevation of pH to 8.0, in its turn, decreases the inhibition of ATP-hydrolyzing activity by calcium. With the increase of K+ concentration (in contrast to Na+) the sensibilization of Na+, K(+)-ATPase to Ca ions is observed. In the presence of potassium ions Mg2+free effectively modifies the inhibitory action of Ca2+free on this enzyme. Ca2+free (0.16-0.4 mM) decreases the sensitivity of Na+, K(+)-ATPase to action of the specific inhibitor ouabain in the presence of ATP. In the presence of AcP (phosphatase reaction) such a change of enzyme sensitivity to ouabain isn't observed. The influence of membranous effects of Ca2+ on the interaction of Na+, K(+)-ATPase with the essential ligands and cardiosteroids is discussed.

Mechanism of metabolic adaptation

Abstract: The paper presents results of investigations on some mechanisms of metabolic adaptation in mammals. There are four sections in the tissue metabolic system of acid-base homeostasis: polyamines as factors of metabolic adaptation; significance of carbon dioxide for metabolic response formation in hypobiosis; polyamines metabolism in hypobiosis. Peculiarities of intermediate metabolism have been analyzed in animal tissues under the changes in H+, CO2 and HCO3- concentrations. Basing on a new interpretation of the experimental data and detected regularity in the metabolism, conclusion on the existence of a new acid-base homeostasis system in the tissues has been made. The results of polyamines metabolism investigations in the mammals under the stress have been described. The experimental data make us to believe that changes in polyamines synthesis and ODC activity in particular, is a part of stereotype nonspecific response to any stress impacts and one of the factors of cell metabolic adaptation. Some new data on mechanisms of formation and control of metabolic status of animals in the natural and artificial hibernation have been presented. The key idea is that in the state of hypobiosis the carbon dioxide (HCO3-) appears as a regulatory factor of metabolic adaptation, which is able to realize its action directly via affecting numerous biochemical events. The participation of polyamines in adaptive metabolic response to hybernation factors is suggested. Some peculiarities of ornithine decarboxilase and transglutaminase activity during the different stages of genuine and artificial hypobiosis have been demonstrated.

[Proteinase-proteinase inhibitor complex in rats under oxidative stress caused by administration of cobalt chloride].

Abstract: Mechanisms of proteinase-inhibitor proteinase system response was estimated following of cobalt chloride injection. The increase proteinase activity, which led to significant decrease of alpha-2-macroglobulin (alpha-2-MG) level was established that indicated to the removal of the proteinase in complex with alpha-2-MG from the organism. Increase of alpha-1-proteinase inhibitor (alpha-1-PI) trypsin-inhibitory activity in the kidneys testify about removal of oxidative alpha-1-PI.

[alpha-Latrotoxin as an instrument for studying neurosecretions].

Abstract: alpha-Latrotoxin, a presynaptic toxin from black widow spider venom Latrodectus mactans tredecimguttatus, triggers exocytosis in a variety of neurosecretory cells both in the presence and absence of calcium in the medium. The toxin interacts with two types of membrane the receptors which belong to different families of neuronal proteins and have different structures. Calcium-dependent receptor of alpha-latrotoxin is identified as neurexin I alpha and belongs to the family of neurexins. This family is selectively expressed in nerve tissue. The calcium-independent receptor of alpha-latrotoxin belongs to the family of G-protein-coupled receptors and proteins which homologous to it are found in heart, lung, kidney and spleen tissues. As a result of alpha-latrotoxin interaction with membrane receptor in the calcium medium the toxin forms the ionic channels in plasmalemma and enhances its calcium permeability. The effects of alpha-latrotoxin on exocytosis in the calcium and calcium-free media and question concerning coupling of channel-forming and secretogenic properties of alpha-latrotoxin are discussed.

Mechanism of fibrinolysis and thrombolytic therapy

Abstract: The thrombolytic treatment with plasminogen activators, such as physiological tissue-type plasminogen activator (t-PA), suffers from a number of significant limitations. There is a resistance to reperfusion and acute coronary reocclusion. The peculiarity of t-PA and one-chain urokinase treatment is their using in very high doses. Thus the process of thrombolytic therapy is proceeding with a deviation from the fibrinolytic mechanism, which is needs of a little quantity of tissue-type plasminogen activator and provides the physiologic thrombolysis without systemic complication. The estimation of this disaccordance suggests, the possible reasons of these complications.

Coagulation factors and fibrinolytic system in subretinal liquid in patients with rheumatogenous retinal detachment

Abstract: The work deals with estimation of some factors of blood coagulation and fibrinolytic systems, which include antithrombin III, factor X, prothrombin, plasminogen, protein C concentrations in the subretinal fluid of the patients with rhegmatogenous retinal detachment retina. The tendency to increase of the blood coagulation and fibrinolysis factor levels, except protein C, was revealed in the patients with complicated forms of the disease. The investigations mentioned above are capable of serving as a diagnostical and forecasting test characterizing the rhegmatogenous retinal detachment retina and surgical treatment proceeding.

Lipid peroxidation in the lungs upon inhalation exposure to low concentrations of lead salts

Abstract: Effects of inhalation with low concentration lead salts on lipid peroxidation intensity and antioxidative system state were investigated in respiratory pulmonary branch in rats after both short-term and chronic exposures to 001% Pb(CH3COO)2 It was shown that the short-term toxic action had considerably affected on the antioxidant system state in lungs as a result of tissue antioxidative activity exhausting Under the chronic lead inhalation penetrating disorders in adaptive mechanisms were found It was reflected in lipid peroxidation product accumulation and decreased parameters of antioxidant defense, and development of energy deficiency