Исследовано влияние курения на содержание маркеров апоптоза: белков Bcl-2 и p53 в плазме крови, а также на активность антиоксидантных (АО) ферментов: Cu, Zn-супероксиддиссмутазы (СОД), глутатионпероксидазы (ГП), глутатионредуктазы (ГР), глутатионтрансферазы (ГТ), каталазы и содержание малонового диальдегида (МДА) в эритроцитах крови у здоровых доноров и пациентов с онкологическими заболеваниями. Среди здоровых курильщиков выявлены 2 группы доноров: с высоким уровнем белка Bcl-2 и активностей СОД и ГП и со сниженным уровнем Bcl-2 по сравнению с некурящими. В группе онкологических больных, как у курящих, так и у некурящих, определено существенное повышение уровня белка р53 и увеличение активности ГТ. Обнаружена обратная корреляция между МДА и ГТ в группе курящих здоровых доноров и прямая корреляция между МДА и р53 у онкологических больных. Результаты свидетельствуют о взаимосвязи компонентов ферментативной защиты и процессов перекисного окисления липидов с содержанием белков регуляторов апоптоза у здоровых курящих и у пациентов с онкологическими заболеваниями.

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.

Increased oxidative stress is known as significant part of pathogenesis of smoking-related cancer. The study was aimed to investigate changes in antioxidant status induced by chronic cigarette smoking in cancer patients and healthy subjects. We examined the venous blood samples of healthy subjects, both smokers and non-smokers and of patients with smoking-related cancer, both smokers and non-smokers. The activities of 5 antioxidant enzymes: glutathione peroxidase, glutathione transferase (GST), glutathione reductase, superoxide dismutase and catalase were measured. Parameters of oxidative damages to cellular structure (level of malonic dialdehyde, microviscosity of erythrocytes membrane and number of leukocytes DNA breaks) were determined. The multi-factorial analysis of data was carried out using binary logistic regression. The results show a statistically significant increase in GST activity and DNA breaks (DSB and SSB) as well as decrease of tau(CII) parameter in cancer patients compared with healthy subjects. In the cancer patients no influence of smoking on studied parameters was found. Correlations of parameters within cancer patients and healthy subjects group did not coincide with each other. Studied parameters of AO status and damages to cellular structures in human blood are changed by tumor process indicating the augmentation of oxidative stress. The study demonstrated potential applicability of a statistical model based on the evaluated markers to determine the risk of cancer incidence in healthy smokers.

Cigarette smoke contains a number of oxidising compounds, reactive oxygen species, and carcinogens damaging genome, membranes and cellular macromolecules. Oxidative stress causes lipid peroxidation, protein modification and DNA damage. The aim of this study was to investigate changes in antioxidant status and parameters of structural damages induced by chronic cigarette smoking in healthy subjects. We examined the blood samples of healthy subjects, both smokers (n=25) and non-smokers (n=29). The activities of 5 antioxidant enzymes: glutathione peroxidase (GPx), glutathione transferase, glutathione reductase (GR), superoxide dismutase (SOD), and catalase were measured. Parameters of oxidative damages of cellular structure (level of malonic dialdehyde, membrane microviscosity in erythrocytes and numbers of leukocyte DNA breaks) were determined. The results show a statistically significant increase in GPx and SOD activity in smokers compared to non-smokers. There were GPx and SOD activity and the number of DNA breaks increase and GR activity decrease in smokers of high intensity compared to smokers of low intensity and non-smokers. In the ex-smokers all these parameters were lower than in high intensity smokers. The data obtained show the increased oxidative stress in healthy smokers compared to healthy non-smokers and the relationship between smoking intensity and the extent of damage.

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.

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.

The rate of accumulation of conjugated dienes of polyunsaturated fatty acids was measured during free-radical oxidation of linoleic acid (18:2n-6, LA), α-linolenic acid (18:3n-3, α-LNA), and γ-linolenic acid (18:3n-6, γ-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 α- and γ-LNA. The antioxidant activity of β-carotene, in contrast to homogeneous solutions, in both micellar systems studied depended on the degree of PUFA unsaturation. We found that 5 μM β-carotene effectively inhibited the LA oxidation (almost by 90%), whereas the oxidation of α-LNA and γ-LNA was not inhibited by β-carotene even at much greater concentration (30 μM). The paradoxical discrepancy between the extent of unsaturation and the PUFA oxidation rate, as well as a decrease in the efficiency of β-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 doublebond number greater than two exhibit different polarity.

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.

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.

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 (Cs-137, 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.

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.

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 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), glutatione 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 manlier 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.

Probucol in concentrations of 10–15 μM effectively inhibits Cu2+-induced free radical oxidation of native low density lipoproteins and in concentration of 100 μM it inhibits lipoperoxide formation. The mean plasma concentration of probucol in patients receiving 250 mg of this drug is 25 μM. Both 250 and 1000 mg probucol daily during 3–6 month block the oxidation of isolated low density lipoproteins. Electron paramagnetic resonance spectrometry data showed that probucol incorporatedin vivo into lipoprotein particles interacts with lipid radicals yielding long-lived phenoxyradicals. Probucol can be used in complex therapy of atherosclerosis as an antioxidant drug and its dose required for lipoprotein protection against atherogenic modification can be decreased to 250 mg/day.

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.