Pathomorphological Changes in the Brain in Dynamics of Long-Term Dust Exposure.

Histological and morphometric studies of brain autopsy material showed that the development of hypoxic changes in miners starts at the early stages of working in the dusty atmosphere. Edema of the pericellular and perivascular zones and the pia mater, degenerative changes in some nerve cells and even their loss and formation of gliosis foci were identified. The revealed changes in neurons progressed with increasing the duration of working under hazardous conditions.

Participation of Free-Radical Processes in Structural and Metabolic Disturbances in the Lung Tissues Caused by Exposure to Coal-Rock Dust and their Adaptogenic Correction.

Adaptive correction of structural and metabolic disturbances in the lungs caused by longterm exposure to coal-rock dust were studied in experiments on rats. It was shown that the complex antioxidant preparation containing dihydroquercetin compensated disturbances in the redox balance in the lung tissue, prevented the formation of dust granulomas, and reduced the severity of degenerative changes in the bronchopulmonary system.

Pro- and Antioxidant Systems in the Lower Portion of Rat Brainstem during Hydroxybutyrate-Induced Pathological Periodic Breathing.

Activities of superoxide dismutase and catalase characterizing antioxidant status of the nervous tissue and its resistance to free radical oxidation were measured in the brainstem of rats with hydroxybutyrate-induced pathological periodic breathing. Hydroxybutyrate modified the pro- and antioxidant status in the brainstem respiratory center. It markedly inhibited catalase activity; in rats without the signs of periodic breathing, hydroxybutyrate up-regulated superoxide dismutase activity and to a lesser extent increased the resistance of the membrane structures in the medulla oblongata to induction of free radical oxidation. In rats with periodic breathing pattern, hydroxybutyrate induced more pronounced increase in the sensitivity of membrane structures in the medulla oblongata to induction of free radical oxidation.

Experimental studies of intracellular liver protective mechanisms in development of chronic fluorine intoxication.

The authors studied intracellular liver protective mechanisms in development of chronic fluorine intoxication. Findings are that synthesis of protective proteins HIF-1α, HOx-1, HOx-2 and HSP72, restricting free radical oxidation in hepatocytes increased in liver at early stages (1-3 weeks) of exposure to fluorine. At late terms of chronic fluorine intoxication (6-12 weeks), damaging effects of fluorine result from its genotixicity - ability to suppress synthesis of intracellular protective proteins and enzymes of main metabolic cycles in liver.

Experimental Study of the Mechanisms of Intracellular Defense in Cardiomyocytes Associated with Stages of Anthracosilicosis Development.

Mechanisms of intracellular defense of rat cardiomyocytes were studied in dynamics of anthracosilicosis development induced by long-term inhalation of coal and rock dust. It was shown that synthesis of transcription factor HIF-1α and protective proteins increased in the heart at the early stages of coal and rock dust inhalation (1-3 weeks), and these changes limited the development of free radical oxidation and activated metabolism of glucose and fatty acids. Exposure to coal and rock dust for 6-12 weeks activated free radical oxidation and decreased basal metabolism in cardiomyocytes.

Mechanisms of intracellular defense and activity of free radical oxidation in rat myocardium in the dynamics of chronic fluorine intoxication.

The mechanisms of intracellular defense and activity of free radical oxidation in the myocardium were studied in the dynamics of chronic fluorine intoxication. At the early stages of fluorine intoxication (day 3-week 3), the concentrations of defense proteins HIF-1α, HSC73, and HOx-2 and activity of the main metabolic enzymes increased, which promoted maintenance of cardiomyocyte structure and function at the normal physiological level. At late stages of fluorine intoxication (weeks 6 and 9), metabolic changes in the myocardium attest to high strain of the adaptive mechanisms.

[The resistance of low brainstem tissue to free radical oxidation in rats during periodic breathing following hydroxybutyrate treatment].

We evaluated tissue resistance to free radical oxidation, in pentobarbital-anesthetized mongrel albino male rats during pathologic periodic breathing following hydroxybutyrate (GHBA) administration. It was shown that GHBA modulated pro- and antioxidant status of brain tissue. In the absence of periodic breathing after GHBA, decreases in resistance of brainstem tissue membranes to induction of free radical oxidation were slightly pronounced. Rats with GHBA-induced periodic breathing exhibited increased membrane sensitivity of medullar neurons to induction of free radical oxidation. We suggest that cellular metabolism and/or membrane mechanisms of respiratory rhythm-generating neurons play a role in the pathogenesis of periodic breathing.

[The experimental search of immunological criteria for identifying stages of development of chronic fluoride intoxication].

The experiment has shown the staging of the development of immune response to the chronic fluoride intoxication. Diagnostic criteria of the initial compensation stage are: leukocytosis against the background of reduced number of lymphocytes and increased one of monocytes; high levels of ceruloplasmin in blood plasma, a progressive increase in TNFalpha and cytokine IL-10. At the decompensation stage there are: leukocytosis with increased number of neutrophils; low levels of ceruloplasmin and the cytokines IL-1beta, IL-4 and the high level of TNFalpha, IL-6, IL-10. At the stage of exhaustion there are: leukopenia against the background of lymphocytosis, a high level of Hp, the low values of the level of IgM, IgG.

[Specificity of cellular response to various occupational toxicants].

The article covers study concerning influence of coal rock dust and high fluorine concentrations on energy metabolism and oxidation-reduction reactions in blood WBC of experimental rats. The authors demonstrated that the cells vary in response to long action of coal rock dust and high fluorine concentrations.

[Reactive oxygen species and redox-signaling during adaptation to changes of oxygen level].

Review of last 15 years literature and own experimental data on role of reactive oxygen species (ROS) and redox signalization in induction of cell protective systems and development of adaptive resistance. Modem ideas of ROS involvement in redox signalization, induction of transcription factors and protective proteins, ways of cell response to ROS, essential limitations of exogenic antioxidants are shown. Concept of ROS involvement in non-specific component of increase resistance is introduced. Peculiarities of author's method of adaptation to change oxygen level are discussed. Experimental data on efficacy of adaptation to periodic hypoxiahyperoxia from ROS-induced stresses are presented.

[Dynamic changes in transcription factor HIF-1alpha, rapid response protein, and membrane structure resistance following acute hypoxia].

Within the last decade, a great number of reports have discussed cellular redox signalization depending on the levels of oxygen and reactive oxygen species (ROS). Experiments have proven that ROS can not only be damaging, but are also able to induce the synthesis of cell defense systems. The initiation of redox signal system results in the induction of various transcription factors which response to hypoxia and hyperoxia, an increase in ROS, oxidants etc. The most significant of them is HIF-1alpha, transcription factor playing an important role in the regulation of oxygen homeostasis in the cell as well as in resistance of the heart and the brain to ischemic and reperfusion injury. About 60 genes activated by HIF-1 are known today; among these are genes that code defense systems: cellular antioxidant system, peroxiredoxines, prostaglandins, heme oxygenase, and heat shock proteins. However, despite numerous data on HIF-lalpha expression stimulation or suppression in exposure to ischemia or hypoxia, they are rather contradictory. In this study, changes in HIF-la induction three, six, and twelve hours after acute hypoxia (8% O2 during one hour) were evaluated, and the dynamics of HIF-1alpha level following hypoxia was compared with the dynamics of the levels of rapid response protein, such as inducible heme oxygenase form, HSP70 stress inducible protein, and antioxidant defense enzymes. The findings indicate a nonlinear dynamics of changes in the levels of transcription factors and rapid response proteins with protective function, tissue specificity of their induction, a direct correlation between HIF-1alpha and superoxide dismutase levels in the heart and HIF-1alpha and HSP70 levels in the liver. The stability of membrane structures of different organs and cardiac sarcoplasmatic reticulum Ca pump are maintained by activation of redox signalization and compensatory synthesis of defense proteins.

[Variability of hemodynamic parameters and resistance to stress damage in rats of different strains].

Total power of heart rate variability and baroreflex sensitivity were significantly smaller in the August rats than in the Wistar rats, but adrenal and plasma catecholamine contents were considerably higher in the former ones. 1 hour after stress (30 min in cold water), plasma catecholamine was increased 2-fold in Wistar rats, while in August rats the adrenaline concentration increased only by 58% and the were no changes in noradrenaline content. At the same time, activation of catecholamine metabolism in the adrenal glands was similar in both groups. The oxidative stress induced by hydrogen peroxide depressed the contractile function of isolated heart in the August rats to a smaller extent as compared to Wistar rats, control ones and after the cold-water stress. This effect correlated with more pronounced stability ofantioxidant enzymes in the August rats. It seems that the greater resistance to stress damage in the August rats is mediated by enhanced power of defense mechanisms both at systemic and cellular levels.

Adaptation to periodic hypoxia and hyperoxia improves resistance of membrane structures in heart, liver, and brain.

A novel principle of short-term periodic adaptive training by varying the oxygen level from hypo- to hyperoxia is substantiated both theoretically and experimentally. Short-term adaptation to hypoxia-normoxia produced a membrane-protective effect in the heart and cerebral cortex, but increased the sensitivity to free radical oxidation and decreased the level of components of the antioxidant defense system in the liver. Hypo-hyperoxia adaptation produced a membrane-stabilizing effect in the heart, brain, and liver, which was more pronounced compared to the effect of hypoxia-normoxia training. In contrast to hypoxia-normoxia adaptation, in case of hypo-hyperoxia training the adaptive defense developed as early as 15 days after the start of training.

Ca(2+) transport into sarcoplasmic reticulum and immediate-early response proteins in the myocardium of rats resuscitated after systemic circulatory arrest.

Activity of antioxidant defense enzymes and content of stress protein HSP70 in the heart increased in passive and, to a lesser extent, in active rats on day 7 of the postresuscitation period after systemic circulatory arrest. The resistance of membrane structures in the heart to endogenous damaging factors in passive rats was lower than in active animals. The degree of compensation in active rats was much higher than in passive animals at these terms of the postresuscitation period.

[Contractile function of the heart and myocardium antioxidant system in rats of August and Wistar strains during ischemia and reperfusion]. / Sokratitel'naia funktsiia serdtsa i antioksidantnaia sistema v miokarde u krys linii Avgust i Vistar pri ishemii i reperfuzii.

In August rats, local myocardial ischemia caused by 30-min occlusion of the coronary artery induced a slight depression of the contractile function of the heart; the latter was restored after 15-min reperfusion more rapidly than in Wistar rats. In August rats, the activities of antioxidant protection enzymes were lower than in Wistar rats. In comparison with Wistar rats, these enzyme activities were decreased in a lesser degree under ischemia and were restored in a greater degree under reperfusion. It may thus be concluded that the higher stability of antiradical protection parameters in August rats is one of the mechanisms responsible for the enhanced resistance of the heart to ischemia- and reperfusion-induced injuries.

Heart resistance to oxidative stress in rats of different genetic strains.

In August rats reperfusion after regional myocardial ischemia in situ or intracoronary administration of hydrogen peroxide less significantly suppressed contractile activity of the heart compared to Wistar rats. Activities of catalase and superoxide dismutase in the myocardium during reperfusion remained unchanged in August rats. In Wistar rats a profound inhibition of cardiac function was accompanied by a decrease in enzyme activity.

[The protective effect of preliminary adaptation to the stress from disorders of the gas-transport function of the blood in hemorrhagic shock]. / Zashchitnyi éffekt predvaritel'noi adaptatsii k stressu ot narushenii gazotransportnoi funktsii krovi pri gemorragicheskom shoke.

To prevent disturbances of blood gas-transport function in hemorrhagic shock, we used cross-over protective effect of adaptation to short-term immobilization stress. Adaptation of rats to stress was associated with a rise in baseline arterial blood, pH in venous blood; fall in PO2, PCO2,P50. Stress-adapted rats appeared more resistant to blood loss. Gas transport 1 hour after hemorrhage was better than in non-adapted animals demonstrated more active compensatory reactions in l low hypoxic damage to the tissues. 2.5-h survival after start of bleeding in control animals made up 35%, in the group of adapted animals--67%. Thus, adaptation to short-term immobilization stress is a non-pharmacological method to prevent hemorrhagic shock.