[Mitochondrial thiol-disulfide system under acute hypoxia and hypoxic-hyperoxic adaptation].

The authors investigated the state of mitochondrial glutathione pool (reduced and oxidized glutathione, protein-GSH mixed disulfides), content of carbonyl groups and free sulfhydryl groups of proteins, protein expression of key mitochondrial antioxidant enzymes such as glutathione peroxidase and thioredoxin reductase as well as activity of glutathione reductase, glutathione peroxidase and glutaredoxin in the liver mitochondria of rats exposed to acute hypoxia after prolonged hypoxic-hyperoxic training (HHT). It was shown that the preliminary HHT reduced the intensity of proteins oxidative modification under acute hypoxia, activated the mitochondrial antioxidant defense as well as affected the thiol-disulfide exchange, redox balance in mitochondria, modulated the S-glutathionylation/deglutathionylation process in mitochondria membranes.

[Phase changes of energy metabolism during adaptation to immobilization stress].

In stress, it was showed the organ and tissue changes associated with damage by lipid peroxides, and the disrupted barrier function. As a consequence, it was to lead to a syndrome of "stress-induced lung" and violation of oxygen delivery to the tissues and hypoxia. Purpose of the study was to investigate the dynamics of changes in gas exchange, blood glucose, body temperature, oxidant and antioxidant system activity, as well as mitochondrial respiration by Chance under the influence of chronic stress (6-hour immobilization daily for 3 weeks). It was identified 4 phase changes of energy metabolism in the dynamics of chronic stress. In the first phase, hypomethabolic, instability oxidative metabolism, decreased oxidation of NAD-dependent substrates, significant elevation of FAD-dependent substrates oxidation and low MRU were found. The activity of superoxide dismutase (MnSOD) was increased; it was occurred on a background low activity of glutathione peroxidase, and of misbalanced antioxidant system. After seven immobilizations, second phase-shift in energy metabolism, was observed, and then the third phase (hypermetabolic) started. It was characterized by gradual increase in oxidative metabolism, the restoration of oxidation of NAD-dependent substrates, MRU, as well as optimizing balance of oxidant and antioxidant systems. The fourth phase was started after 15 immobilizations, and characterized by the development of adaptive reactions expressed in increased tolerance of energy metabolism to the impact of immobilization. The results are correlated with changes in the dynamics of blood corticosterone. Thus, it was found the phase character of the energy metabolism rebuilding during the chronic stress.

[Disturbances of oxygen-dependent processes in periodontal tissues under prolonged immobilization stress and ways of their pharmacological correction].

Influence of prolonged immobilization (6 h strict horizontal position of rats in the tight containers daily for 2 weeks) on oxygen tension, oxygen consumption, pro-/antioxidant balance, and energetic metabolism of soft and hard periodontal tissues has been investigated. It was established that prolonged immobilization stress resulted in marked decrease in the gum tissue PO2 (36%) and in the bone tissue oxygen consumption rate (46%) compared to control. It was also determined that prolonged stress led to a reduction in the gum mitochondrial respiration rate. The latter was more expressed in case of the NAD-dependent substrate oxidation than of the FAD- dependent one. It was determined that the prolonged stress results in intensification of peroxide processes and depletion of antioxidant protection of soft tissues of periodontum. It was found that Thiotriazolin and Actovegin have modified and diminished stress-induced disorders in the soft and hard periodontal tissues oxygen homeostasis under prolonged immobilization stress.

[Continuous adaptation of rats to hypobaric hypoxia prevents stressor hyperglycemia and optimizes mitochondrial respiration under acute hypoxia].

Oxygen consumption, glucose blood level and liver mitochondrial respiration were investigated in male Wistar rats permanently living in middle altitude (2100 m, Elbrus region). The animals were characterized by reduced body oxygen consumption and blood glucose level, as well as by intensified utilization of NAD-dependent substrates in mitochondrial respiratory chain with increasing indices of ADP-stimulated respiration in comparison with plains rats. As a result of adaptive rebuilding of oxidative metabolism in rats--inhabitants of midlands, the nature and severity of metabolic responses to acute hypoxia were also changed. After lifting in barochamber to a "height" of 5600 m during 3 hours, plains rats transiently demonstrated hypometabolic and hyperglycemic reactions. A rapid adaptation of mitochondrial function occurred due to increase in the rate of FAD-dependent substrate oxidation accompanied by a decrease in the effectiveness of phosphorylation. In midland rats, by contrast, hypoglycemic reaction was developed, and further reduction of aerobic metabolism was limited. Rapid adaptation of mitochondrial function to acute hypoxia in those rats was more intense than in the plains animals. This was achieved by a significant increase in the rate of NAD-dependent substrate oxidation, especially lipids, and an improved efficiency of mitochondrial respiration and an increased economy of oxygen utilization.

[Changes in mRNA and protein expression of antioxidant enzymes in children with bronchial asthma after interval hypoxic training].

The effect of 10 days of interval hypoxic training (IHT) on the mRNA expression and protein content of antioxidant enzymes (superoxide dismutase, catalase and glutathione-S-transferase) in leukocytes of children with bronchial asthma (BA) was investigated. It was shown that after sessions of IHT the mRNA expression of superoxide dismutase decreased by 32.5% (P < 0,05), but the level of protein was unchanged. The level of catalase gene mRNA and protein content in leukocytes after IHT increased by 67% and 13% accordingly. We detected a 90% increase in glutathione S-transferase level following IHT.

[Glutathione system adaptation to acute stress in the heart of rats during different regimes of hypoxia training].

The intensity of lipid peroxidation (LPO), reduced and oxidized glutathione (GSH and GSSG) contents, glutathione reductase, glutathione peroxidase, glutathione-S-transferase, glucose-6-phosphate dehydrogenase (G-6-PDH), and NADP-isocitrate dehydrogenase (NADP-IDH) activities were studied in the heart of male rats exposed to two modes of intermittent hypoxic training (IHT): I-breathing in normobaric chamber with 7% O2 gas mixture for 5 min with 15 min normoxic intervals 4 times daily during 3 weeks; II-breathing by 12% O2 gas mixture in the same manner). After adaptation to hypoxia, the rats were subjected to 6h-immobilization stress. It has been shown that stress action after IHT (regime I) caused the increase in LPO and the shift of GSH/GSSG to disulfides. A disbalance in antioxidative defense system was determined by the decrease in glutatione peroxidase, G-6-PDH activities, and GSH content. The support of glutathione reductase activity under stress in this group with simultaneous decrease of enzyme activity in the pentose phosphate pathway was realized through the participation of NADP-IDH. Hypoxic training in regime II induced LPO decrease in the heart tissue after stress. The increase in the heart GSH content, optimal balance of glutathione-related enzymes in this group evidences for the dependence of adaptation effects on the vigor of hypoxic exposition. Our results suggest the active participation of glutathione system in the formation of adaptation reactions under the extreme factor influences through the action on intracellular red/ox potential as well as effectiveness of antioxidant defense.

[Genetically determined organ-specific changes of some tissue morphometric characteristics under the various exogenous influences].

Organ-specific alterations of ultrastructure and morphofunctional condition in different organism's tissues, which could evidence of the genetic factors inclusion under the development of different hypoxic condition in organism, were investigated. The dates obtained indicated the marked organ-specific "structure" reaction of tissues, cells and organelles under various exogenous influences. Such reactions confirm the presence of different genes expression which account for ultrastructure alterations; its activity is determined by a type, intensity, duration of influence as well as organ belonging. Ultrastructural alterations are mainly determined by tissue and cell factors but not by genetically determined system reactions; it is confirmed by various reactions on external factors in animal tissues with different genetically determined oxygen consumption level or genetically determined adaptation to middle-altitude conditions.

[Individual characteristics of human adaptation to intermittent hypoxia: possible role of genetic mechanisms].

The majority of the adaptation processes to hypoxia is based on transcriptional regulation by hypoxia-inducible factors--HIFs. Recently the allele polymorphism of oxygen-dependent degradation domain of HIF-lalpha has been described. It consists in the replacement of cytosine for thymine in 1772 location (C1772-->T). The physiological significance of such replacement is obscure. In the investigation of 26 healthy elderly subjects (58.5 +/- 0.7 yr) we tried to verify whether HIF-lalpha polymorphism in exon 12 may identify individual features of adaptation to intermittent hypoxia training (IHT) (isocapnic hypoxic rebreathing technique, 5-min sessions with 5 min rest intervals, 3 times daily during 10 days). The distribution of HIF-l alpha genotypes for C1772-->T were studied by using the polymerase chain reaction and restriction analysis. We detected that all subjects from the group had C/C genotype. Meanwhile, the broad spectrum of adaptive reactions to IHT was observed, from the best adaptation up to disadaptation. IHT enhanced HVRs in the range of 167% - 5%, blood malon dialdehyde content varied from a decrease by 46% up to an increase by 88%, the changes of superoxide dismutase activity varied from +64% to -56% etc. These results suggest that the C1772-->T polymorphism in HIF- 1alpha does not contribute to individual peculiarities of adaptation to IHT. Because the activity of HIF-lalpha is regulated by multiple steps including the transcriptional level, the effect of the polymorphism in enother exons on the adaptive reactions remains to be elucidated.

[Effect of intermitent hypoxia on ultrastructure and prooxidant-antioxidant balance in the soft tissue of the periodontium in acute immobilization stress].

The changes of prooxidant-antioxidant balance and morphofunctional state of soft tissue of paradontum under the acute immobilization stress, intermittent hypoxia and its complex influence were investigated. It was shown, that intermittent hypoxia can stimulate own endogenous mechanisms of nonspecific resistance, such as antioxidant protection in soft tissue of paradontum. Normalization of the prooxidant-antioxidant balance under immobilization stress after intermittent hypoxia essentially improved the morphofunctional state of tissue investigated with decrease of edema and improvement of mitochondria apparatus ultrastructure.

[Characteristics of changes in respiratory function of humans after a long stay in Antarctic region].

Fifteen participants of the Antarctic expedition (men, 27-51 years old) have been investigated after their return from a one-year stay there. All subjects have signs of latent hypoxia. Compensation of hypoxic reactions depended on the initial state of organism oxygen regimen as well as on the features of a genotype. It was supposed that, after a long stay by a person in the coastal Antarctic conditions, the latent form of hypoxia could develop. The latter was accompanied by reorganizations of oxygen regimen and determined by specific features of a genotype.

[Effect of intermittent hypoxic hypoxia on energy supply of rat skeletal muscle during adaptation to physical load].

The experiment, on Wistar male rats was carried out to investigate influence of endurance training (swimming with load 7.0 +/- 1.3% body weight, 30 min a day, during 4 weeks) and additional intermittent hypoxic training (12% O2 in N2 - 15 min, 21% O2 - 15 min, 5 sessions a day, during the first 2 weeks) on the following parameters: ADF-stimulated mitochondrial respiration, lactate/pyruvate ratio, succinate dehydrogenase activity, and lipid peroxidation in skeletal muscle. The next oxidation substrates were used: 1 mmol/l succinate and 1 mmol/l alpha-ketoglutarate as well as the next inhibitor succinate dehydrogenase 2 mmol/l malonate. It was shown that physical work combined with intermittent hypoxic training led to the increase of mitochondrial respiration effectiveness in muscle energy supply under alpha-ketoglutarate oxidation in comparison with succinate oxidation as well as to the decrease of succinate dehydrogenase activity and lipid peroxidation. The study suggested that these changes may correct mitochondrial dysfunction under intensive muscular work.

[Effect of intermittent hypoxic training on indices of adaptation to hypoxia in rats during physical exertion]. / Vplyv interval'noho hipoksychnoho trenuvannia na pokaznyky adaptatsiï shchuriv do hipoksiï navantazhennia.

The aim of this study was to investigate physical endurance, maximal oxygen uptake, oxygen partial pressure, and pH in blood and skeletal muscle as well as the muscle metabolic parameters (lactate and pyruvate concentration, lactate/pyruvate and NAD/NADH ratios, succinate dehydrogenase activity, ADP-stimulated mitochondrial respiration) under various regimen of combination of endurance training with intermittent hypoxic training (IHT) in adult Wistar rats. It was shown that physical endurance, maximal oxygen uptake, and muscle PO2 (PmO2) were maximally increased in those animals who simultaneously underwent endurance training and IHT. The same animals demonstrated the minimal decrease in PmO2, blood and muscle pH under testing intensive physical workload. The latter led to the lesser shifts in metabolic parameters in the muscle of rats adapted both to IHT and endurance training than in rats adapted to endurance training only. The combined effects of IHT and adaptation to load hypoxia resulted in an increase of the role of NADH - oxidation pathway in the mitochondrial energy production.

[Oxygen transport in skeletal muscles working with its maximum consumption during hypoxemia]. / Transport kysniu v skeletnomu m'iazi pry roboti z maksymal'nym ioho spozhyvanniam za umov hipoksemiï.

The influence of acute hypoxia (35 < or = PaO2 < or = 100 mmHg) on the values of VO2max and parameters of oxygen transport in muscle working at VO2max was studied under different values of muscle blood flow F (80 < or = F < or = 120 ml/(min 100g), blood pH (7.0-7.6), and different diffusion conditions. Investigations were performed on a computer model of O2 delivery to and O2 consumption in the working muscle. VO2max, pvO2, PO2- and VO2-fields in the muscular fiber were calculated. It was shown that the greater the degree of arterial hypoxemia, the lower the muscle VO2max and PvO2 values. The greater the blood flow through muscle, the greater the VO2max. The diffusion conditions produced a powerful influence on the VO2max value. However, with an increasing degree of arterial hypoxemia, the effect of F, intercapillary distances, and blood pH on the value of VO2max is weakened.

[The antioxidant action of taurine in acute hypoxic hypoxia]. / Antyoksydantna diia taurynu za umov hostroï hipoksychnoï hipoksiï.

It was found that preliminary treatment by amino acid taurine protected rats from lipid peroxidation intensification (expressed in terms of malondialdehyde and conjugated dienes contents) in the liver, brain and heart under acute severe normobaric hypoxic hypoxia. The mechanisms of the antioxidant action of taurine are connected to the prevention of lactate accumulation in tissues and cell membrane structure disorders (expressed in a decrease of membrane Na+, K(+)-ATPase activity). It was also shown that taurine reduced significantly a decrease of glutathione antioxidant system activity protecting tissues against reduced glutathione pool depletion and preventing a decrease of glutathione reductase and glutathione peroxidase activities in acute severe hypoxia.

[The role of oxygen radicals in the physiology and pathology of human sperm]. / Rol' kysnevykh radykaliv u fiziolohiï ta patolohiï spermy liudyny.

Reactive oxygen species in low doses are necessary compound of sperm capacitation and hyperactivation. Superoxide anion, hydroxyl radical and hydrogen peroxide initiate sperm capacitation. The edding of antioxidant enzymes inhibits the spontaneous and induced sperm hyperactivation. The process of capacitation is accompanied with the superoxide anion production output by spermatozoa. High doses of reactive oxygen species block the sperm motility through the inhibition of ATP synthesis by the mitochondrial enzymes and cell membrane compounds injury.