[Effects of smoking and tumor process on the contents of key proteins of apoptosis and activity of antioxidant enzymes in blood].

The effects of smoking on the contents of the apoptosis markers Bcl-2 and p53 proteins in blood plasma; the activity of the antioxidant (AO) enzymes Cu, Zn-superoxide dismutase (SOD), glutathione peroxidase (GP), glutathione reductase (GR), glutathione S-transferase (GST), and catalase; and the content of malondialdehyde (MDA) in erythrocytes from healthy donors and cancer patients were studied. Two groups of donors were revealed among healthy smokers: one with high SOD and GP activities and high Bcl-2 protein levels and the other with lower Bcl-2 levels compared with those found in nonsmokers. In the group of cancer patients (both smokers and nonsmokers), significantly increased p53 protein levels and increased activity of GST were found. A negative correlation between MDA and GST in the group of smoking healthy donors and a positive correlation between MDA and p53 in cancer patients were found. The results suggest a relationship between the components of enzymatic defence and lipid peroxidation and the content of apoptosis regulator proteins in healthy smokers and cancer patients.

[Age-related peculiarities of effect of low dose ionizing radiation on blood antioxidant enzyme system status in Chernobyl's accident liquidation participant]. / Vozrastnye osobennosti vliiania malykh doz ionoziruiushchei radiatsii na sostoianie fermentnoi antioksidantnoi sistemy krovi uchastnikov likvidatsii Chernobylskoi avarii.

Age-dependency of activity of key blood antioxidant enzymes--superoxide dismutase (SOD), glutathione peroxidase and glutathione reductase has been estimated in 104 men and women aged 25-60 years participated in the liquidation of the Chernobyl's accident since 6 years after irradiation. Control group includes 35 age-matched men and women. The results of study on 18 children aged 7-15 years and 5 children aged 2-6 years born by irradiated parents are given as well. Nineteen children were in the control group. Low-dose irradiation was found modify the pattern of age-related dependency of all enzymes studied. Most susceptible chain was enzymes of glutathione cycle both in liquidators and children. Study of late effects has shown that young people (<30 years) as well as children are most susceptible to low-level irradiation whereas most resistant were middle-aged people. This observation should be taken into consideration at selection of high-risk groups in an industry linked with chronic low-dose irradiation.

[Late consequences of action of low doses of ionizing radiation on human enzymatic antioxidant system]. / Otdalennye posledstviia vliianiia malykh doz ioniziruiushchei radiatsii na sostoianie fermentnoi antioksidantnoi sistemy liudei.

Age-related changes in the activity of superoxide dismutase and glutathione peroxidase in the blood of participants of the Chernobyl accident liquidation were studied. According to our findings the people under 30 years old are the most sensitive to irratiation.

Rate of free-radical oxidation of C18 diene and triene fatty acids in aqueous micellar solutions and effectiveness of beta-carotene as an inhibitor of their oxidation.

The rate of accumulation of conjugated dienes of polyunsaturated fatty acids was measured during free-radical oxidation of linoleic acid (18:2n-6, LA), alpha-linolenic acid (18:3n-3, alpha-LNA), and gamma-linolenic acid (18:3n-6, gamma-LNA) initiated by 2,2;-azo-bis-(2-amidinopropane) hydrochloride in aqueous micellar solutions of sodium dodecyl sulfate and sodium cholate. It was shown that, unlike homogeneous solutions, the oxidative stability of PUFAs in aqueous dispersions increased with an increase in the extent of unsaturation. The rate of LA oxidation was more than tenfold greater than that of alpha- and gamma-LNA. The antioxidant activity of beta-carotene, in contrast to homogeneous solutions, in both micellar systems studied depended on the degree of PUFA unsaturation. We found that 5 micro M beta-carotene effectively inhibited the LA oxidation (almost by 90%), whereas the oxidation of alpha-LNA and gamma-LNA was not inhibited by beta-carotene even at much greater concentration (30 micro M). The paradoxical discrepancy between the extent of unsaturation and the PUFA oxidation rate, as well as a decrease in the efficiency of beta-carotene-dependent inhibition of oxidation of more polyunsaturated fatty acids in reactions conducted in aqueous dispersions is consistent with the model according to which the peroxyl radicals of LA and fatty acids with the double-bond number greater than two exhibit different polarity.

Imbalance in the enzymatic system of production and consumption of active oxygen species in liver of AKR mice with spontaneous leucosis.

Activities of protective antioxidant enzymes, the rate of superoxide formation (v) in microsomal membranes and submitochondrial particles (SMP), and the concentrations of reduced and oxidized glutathione in cytosol were studied in the liver of AKR mice during the development of spontaneous leucosis. It was found that in the latent period of leucosis (mice of 3-6 months of age) the glutathione reductase (GR) activity in cytosol and mitochondria decreased and v in SMP increased. The increase in v in SMP did not result in the induction of Mn-SOD. In this stage of leucosis, the activities of Cu,Zn-SOD, GSH-Px, and G-6-PDH in cytosol were unchanged; at the same time, the GR activity and the concentration of reduced glutathione smoothly decreased. In the stage of developed leucosis (mice of 7-9 months of age), non-synchronous changes in the antioxidant system resulting in the shift of metabolism towards the prooxidant state were found. Comparison of our findings and the literature data demonstrates that the observed decrease in the SOD/GSH-Px ratio, the decrease in GR activity, and the increase in the v/Mn-SOD activity ratio are typical for pre-neoplastic changes in cell metabolism.

[The systemic response of antioxidant enzymes to the oxidative stress induced by irradiation at low doses]. / Sistemnyi otvet antioksidantnykh fermentov na okislitel'nyi stress, vyzvannyi oblucheniem v malykh dozakh.

As a result of total chronic gamma irradiation of mice (137Cs, 0.6 cGy/day, 9 days) the functioning of superoxide generation and utilisation systems in liver were disturbed. The regulatory links between the activities of superoxide dismutase and glutathione peroxidase are found to be maintained. Postradiation effects were more expressed for a total dose of 1.2 cGy than for a dose of 5.4 cGy, providing support for the hypothesis of delayed reparation as a reason of harmful action of low-dose irradiation.

Changes in superoxide production rate and in superoxide dismutase and glutathione peroxidase activities in subcellular organelles in mouse liver under exposure to low doses of low-intensity radiation.

The functioning of the antioxidant system in mouse liver at increased stationary concentration of active oxygen species induced by whole-body chronic exposure of mice to gamma-irradiation (137Cs, 0.6 cGy/day, 9 days) was studied. Synchronous changes (growth with an extreme) in activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) are found that may be considered as evidence in favor of maintenance of regulatory links in the antioxidant system of liver. The superoxide production rate in microsomes and nuclei also changed with an extreme with the rise in accumulated radiation dose. In microsomes the superoxide production rate reached a maximum at lower doses than the activity of Cu,Zn-SOD did. In nuclei the increase in superoxide production rate was not compensated by the rise in Cu,Zn-SOD activity within the studied dose range. The findings indicate some imbalance between production and consumption of superoxide radicals in microsomes and nuclei; in mitochondria these processes are balanced, leading to more resistance to low-dose irradiation.

Effect of ascorbate and alpha-tocopherol on resistance of beta-carotene to oxidation.

The efficiency of ascorbate and alpha-tocopherol as stabilizers of beta-carotene, which is widely used in complex therapy and prevention of some diseases accompanied by oxidative stress, was studied. The latency of induced beta-carotene oxidation linearly depends on ascorbate concentration, while steady-state rate nonlinearly depends on the concentration of alpha-tocopherol, which attests to involvement of antioxidants in various stages of chain oxidation of beta-carotene.

[Effect of ionol on superoxide radical metabolism in murine liver]. / Vliianie ionola na metabolzm superoksidnykh radikalov v pecheni myshei.

The influence of ionol (100mg/kg) on the rate of superoxide generation (V) and activities of antioxidant enzymes: CuZn- and Mn-SOD, glutathione peroxidase (GSH-Px), glutathione S-transferase (GST) in different subcellular organelles of mice liver was studied. Ionol is shown to result in realiable a synchronous changes of all studied antioxidant enzyme activities in cytosol and whole blood. On the first day the level of these enzymes increased by 1.5 times and on the third day it returned to normal. The obtained data indicate retention of regulatory relation in antioxidant system in liver cytosol within the sector SOD-GSH-Px. In the mitochondria the Mn-SOD activity changes in antibate manner as compared CuZn-SOD activity, on the first day Mn-SOD activity decreases and remains on lowered level during the whole period investigated. In microsomes the value of V is found to be reduced. In the case of SMP on the first day after the administration of ionol V value didn't increase significantly. However, owing to Mn-SOD activity decrease the ratio V/A, showing the level of superoxide radicals in subcellular organelles grows 3-fold. In nuclei V value increases 4-6-fold during 1-3 hours after ionol injection. The data obtained show that administration of high dose of ionol to intact mice suppresses antioxidant enzyme system of mitochondria, induces abrupt production of superoxide radicals in nuclei and reduces of functioning of electron transport chaine in microsomes. The observed disturbances have short-lived character and are normalized during 3 days after administration of ionol. The toxic effects of ionol may be connected with the action of oxidative modification products formed in organism.

[The characteristics of the biological action of low doses of irradiation]. / Osobennosti biologicheskogo deistviia malykh doz oblucheniia.

Biochemical, biophysical and functional properties of the genetic and membrane apparatus of the cell were considered activity and regulatory properties of the membrane and cytosolic enzymes of organs and tissues of mice exposed to radiation in the wide range of doses of 6 to 1800 mGy with the radiation intensity of 4.1 x 10(-3) and 41 x 10(-3) mGy/min. It was shown that the dose-dependence of changes in the investigated properties is of non-linear polymodal (bimodal) nature. The value of the maximum and the dose at which the latter was observed depend on the object's nature, radiation intensity and time passed after irradiation. An essential factor is that sensitivity of molecules, cells, organs and animals exposed to low-dose radiation to other damaging effects changes. The explanation is given in terms of the changes in the relation between the quantity of damages and the activity of reparation systems induced by low-dose irradiation.

[Changes in the intensity of free-radical reactions in the organs of rats under hypokinetic stress and with protection by the delta sleep-inducing peptide and its tyrosine-containing analog]. / Izmeneniia intensivnosti svobodnoradikal'nykh reaktsii v organakh krys pri gipokineticheskom stresse i zashchite del'ta-son-indutsiruiushchim peptidom i ego tirozinsoderzhashchim analogom.

Dynamics of the hypokinesia-induced changes of free radical and malonic dialdehyde content in brain, the changes of respiratory chain state and superoxide dismutase activity in liver of rats has been studied using ESR technique and biochemical methods. The effect of the preliminary injection of DSIP and its analogue ID-2 on these dynamics has also been studied. Using a model system constants of the interaction between DSIP or ID-2 and O2-. have been determined. The data point to the antioxidant effect of the administration of the peptides before hypokinesia. This suggests that the effect involves in mechanisms of the anti-stress action of these peptides.

[Formation of superoxide radicals in membranes of subcellular organelles in regenerating liver]. / Obrazovanie superoksidnykh radikalov v membranakh subkletochnykh organell regeneriruiushchei pecheni.

A correlation between the changes in the rates of superoxide radical generation, upsilon, in microsomes, mitochondria, and nuclei and the Cu, Zn- and Mn-SOD activities in rat liver during the first 5 days after partial hepatectomy, has been studied. Level of upsilon in microsomal and mitochondrial membranes in the regeneration process was reduced. The Cu, Zn- and Mn-SOD activities changed in an extreme and antibate manner: the former was characterized by a minimum, whereas the latter-by a maximum with an extreme on the 3rd day after surgery. Analysis of the correlation between the values of upsilon in the nuclear membranes and cell cycle stages (on a literary basis) revealed that the upsilon was decreased 2 times on the stage of DNA synthesis. When mitosis was at maximum, upsilon showed a 4-5-fold increase in comparison with the control, the Cu, Zn-SOD activity being essentially unchanged. A role of SOD and O2-. in cell division is postulated. O2-. is assumed to play a role in gene expression, disassembly, and regeneration of the nuclear membrane; that of SOD is thought to consist in regulation of the proliferative activity.

[NADH- and NADPH-dependent formation of superoxide radicals in liver nuclei]. / NADH- i NADPH-zavisimoe obrazovanie superoksidnykh radikalov v iadrakh pecheni.

A method for the quantitation of the superoxide radical generation rate (V) in murine liver nuclei by the oxidation of 1-hydroxy-2,2,6,6-tetramethyl-4-oxo-piperidine O2-. radicals with the formation of a stable nitroxyl radical recorded by the EPR method, has been developed. It was shown that NADP- and NADPH-dependent superoxide radical generation is suppressed by superoxide dismutase (approximately by 90%). The Km values for NADH and NADPH are 1.5 x 10(-6) and 4.4 x 10(-7) M, respectively; the maximal rate (0.2 nmol.min-1.mg protein-1) is equal for both substrates. Cyanide (greater than 2 mM) causes a practically complete inhibition of the O2-. generation by both substrates. It is suggested that there exists a single readily autooxidized site of O2-. generation by both substrates for NADH- and NADPH-dependent site of the electron transport chain in nuclear membranes.

[Determination of superoxide dismutase activity in animal tissues by the means of nitroblue tetrazolium]. / Issledovanie opredeleniia superoksiddismutaznoi aktivnosti v tkaniakh zhivotnykh s tetranitrotetrazolievym sinim.

A modified procedure is developed for estimation of superoxide dismutase activity using inhibition of reduction of tetranitrotetrazolium blue (NTB) by the superoxide radicals, produced in the system xanthine-xanthnie oxidase. In the modified procedure initial concentration of NTB was decreased 2-fold, which enabled to increase 1.7-fold the sensitivity of the method. The value of the superoxide dismutase activity was unaltered in mice liver cytosol if the initial rate of NTB reduction varied from 0.01 to 0.02 min-1. The values of inhibition of the enzymatic activity were maintained up to 0.032 min-1 in the systems with purified superoxide dismutase preparations. Separation of low molecular metabolites did not alter these ranges of the constant inhibition values under the conditions of various initial rates of NTB reduction in supernatants.

[Lipid peroxide metabolism in chemical carcinogenesis]. / Metabolizm perekisei lipidov pri khimicheskom kantserogeneze.

Lecithin and kephalin content in the microsomes and mitochondria of the rat liver, and also the activity of enzymatic and nonenzymatic systems of the phospholipid peroxidation showed a sharp change following 3,4-benzpyrene injection. Carcinogenesis is accompanied by significant changes in the lipid peroxides content and in the activity of the enzyme utilizing lipoperoxides (glutathion peroxidase, glutathion reductase). Accumulation of lipid peroxides in the rat liver in carcinogenesis was connected with disturbed balance of the generating systems and detoxication of lipid peroxides in the tumour is attributed to the high activity of the protective enzymatic systems and serves as a reflection of the adaptation mechanisms directed to the maintenance of a high pool of proliferating cells in the tumour.

[Role of lipid peroxides in the pathogenesis of arteriosclerosis. Detoxication of lipid peroxides by the glutathione-peroxidase system in the aorta]. / Rol' perekisei lipidov v patogenese ateroskleroza. Detoksikatsiia lipoperekisei glutation-peroksidaznoi sistemoi v aorte

In aorta of intact rabbits the high activity of glutathione-peroxidase, which detoxicates lipoperoxides, was observed. In aorta of animals with pronounced experimental atheromatosis the enzyme activity did not distinctly differ from the control values. The animals with high initial content of glutathione-peroxidase in aorta were shown to be less subjected to the impairment in alimentary atherosclerosis.