Diazoxide affects mitochondrial bioenergetics by the opening of mKATP channel on submicromolar scale.

Background: Cytoprotection afforded by mitochondrial ATP-sensitive K-channel (mK-channel) opener diazoxide (DZ) largely depends on the activation of potassium cycle with eventual modulation of mitochondrial functions and ROS production. However, generally these effects were studied in the presence of Mg∙ATP known to block K transport. Thus, the purpose of our work was the estimation of DZ effects on K transport, K cycle and ROS production in rat liver mitochondria in the absence of Mg∙ATP.

C Fullerene Prevents Restraint Stress-Induced Oxidative Disorders in Rat Tissues: Possible Involvement of the Nrf2/ARE-Antioxidant Pathway.

The effects of CFAS (50 and 500 g/kg) supplementation, in a normal physiological state and after restraint stress exposure, on prooxidant/antioxidant balance in rat tissues were explored and compared with the effects of the known exogenous antioxidant N-acetylcysteine. Oxidative stress biomarkers (ROS, O·, HO, and lipid peroxidation) and indices of antioxidant status (MnSOD, catalase, GPx, GST, -GCL, GR activities, and GSH level) were measured in the brain and the heart. In addition, protein expression of Nrf2 in the nuclear and cytosol fractions as well as the protein level of antiradical enzyme MnSOD and GSH-related enzymes -GCLC, GPx, and GSTP as downstream targets of Nrf2 was evaluated by western blot analysis.

The protective effect of Hif3a RNA interference and HIF-prolyl hydroxylase inhibition on cardiomyocytes under anoxia-reoxygenation.

The aim of this study was to investigate the molecular mechanisms underlying the protective effects of hypoxia-inducible factor (HIF) signaling pathway activation in cardiomyocytes under anoxia-reoxygenation (A/R) injury. In this study, rat neonatal cardiomyocytes were pretreated with anti-Hif3A/Hif-3α siRNA or HIF-prolyl hydroxylase inhibitor prior to A/R injury. Our results showed that both HIF3A silencing and HIF-prolyl hydroxylase inhibition effectively increased the cell viability during A/R, led to changes in mRNA expression of HIF1-target genes, and reduced the loss of mitochondrial membrane potential (Δψ).

[EFFECT OF CURCUMIN ON MITOCHONDRIAL FUNCTION OF CARDIOMYOCYTES WITH DOXORUBICIN-INDUCED OXIDATIVE STRESS].

We studied the effect of curcumin on the cardiomyocytes viability, processes of oxidative phosphorylation in the mitochondria of cardiomyocytes, their pro- and antioxidant balance in doxorubicin-induced oxidative stress. It has been revealed that administration of doxorubicin to rats led to a significant increase in the secondary products of lipid peroxidation (TBARS) in mitochondria by 21 and H(2)0(2) by 76%, reduction of the enzymatic activity of mitochondrial Mn-SOD by 14% and intensified catalase activity by 80% compared with the control. After combined use of doxorubicin and curcumin the content of TBARS and H(2)0(2) increased by 14 and 26%, respectively, the enzymatic activity of catalase decreased by 28%, and mitochondrial Mn-SOD activity intensified by 9%.

Erratum to: Antarctica challenges the new horizons in predictive, preventive, personalized medicine: preliminary results and attractive hypotheses for multi-disciplinary prospective studies in the Ukrainian "Akademik Vernadsky" station.

[This corrects the article DOI: 10.1186/s13167-016-0060-8.].

The Effect Of NO Donor on Calcium Uptake and Reactive Nitrogen Species Production in Mitochondria.

Background/aims: NO and reactive nitrogen species (RNS) are thought to be physiologically important effectors of mitochondrial calcium transport, but this issue was not studied in a living organism. According to literature, the modulation of Ca2+ uptake could influence RNS production via the action on mitochondrial NO synthase (mtNOS). The aim of this work was to study the effect of in vivo administration of NO donor nitroglycerine (NG) on matrix Ca2+ accumulation, RNS production and mtNOS activity.

siRNA-induced silencing of hypoxia-inducible factor 3α (HIF3α) increases endurance capacity in rats.

Molecular mechanisms of adaptation to exercise despite a large number of studies remain unclear. One of the crucial factors in this process is hypoxia inducible factor (HIF) that regulates transcription of many target genes encoding proteins that are implicated in molecular adaptation to hypoxia. Experiments were conducted on 24 adult male Fisher rats.

Antarctica challenges the new horizons in predictive, preventive, personalized medicine: preliminary results and attractive hypotheses for multi-disciplinary prospective studies in the Ukrainian "Akademik Vernadsky" station.

Background: Antarctica is a unique place to study the health condition under the influence of environmental factors on the organism in pure form. Since the very beginning of the scientific presence of Ukraine in the Antarctic, biomedical research has been developed for the monitoring of individual biomarkers of winterers and medical accompaniment in Antarctic expeditions. The aim of the study was to analyze and discuss the retrospective data of long-term monitoring and observations in Ukrainian Antarctica station "Akademik Vernadsky," providing multi-scale biomedical information with regard to conditions of a perfect isolation from technological and social influences and under extreme environmental factors.

[DOXORUBICIN-INDUCED ALTERATIONS IN PRO-AND ANTIOXIDANT BALANCE AND THEIR CORRECTION BY CURCUMIN IN THE NEONATAL RAT CARDIOMYOCYTES CULTURE].

It was studied the effect of doxorubicin on the HIF system and the pro-antioxidant balance of neonatal cardiomyocytes as well as the possibility of the oxidative stress correcting using curcumin. It has been revealed that the expression of mRNA HIF-1α using doxorubicin at a dose of 0.5 μM was 2.

The effect of atp-dependent potassium uptake on mitochondrial functions under acute hypoxia.

The opening of mitochondrial K(+) АТР-channel (mtK(+) АТР-channel) is supposed to be important in the modulation of mitochondrial functions under hypoxia, but the underlying mechanisms have not been clarified yet. The aim of this work was to study the effect of acute hypoxia on mtK(+) АТР-channel activity and to estimate the contribution of the channel in the modulation of mitochondrial functions. MtK(+) АТР-channel activity was assessed polarographically from the rate of State 4 respiration and by potentiometric monitoring of potassium efflux from deenergized mitochondria.

DOXORUBICIN-INDUSED DISTURBANCES OF CARDIOMYOCYTE CONTRACTILE ACTIVITY.

The aim of our study was to find out the mechanisms of cardiomyocyte contractile activity disturbances under the influence of anthracycline antibiotics and curcumin correction capabilities, to clarify the role of the mitochondrial membrane potential changes in cardiomyocyte contractile activity. It was investigated disturbances of contractile activity of the rat neonatal cardiomyocytes under the influence of anthracycline antibiotics (doxorubicin), and the possibility of correcting these violations using antioxidant curcumin. In addition, there was researched the role of mitochondrial membrane potential changes in reducing contractile activity of the cardiomyocytes.

[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).

[ENERGETIC AND ANTIOXIDANT STATUS OF RAT LIVER MITOCHONDRIA DURING HYPOXIA-REOXYGENATION OF DIFFERENT DURATION].

Dynamics of changes in activity and protein expression of antiradical (MnSOD), glutathione-dependent (glutathione peroxidase, glutathione reductase) and NADP⁺-generated (isocitrate dehydrogenase) enzymes as well as in the energy metabolism indeces in rat liver mitochondria under hypoxia- reoxygenation of different duration (1, 3, 7 14 days) were studied. Prolonged hypoxia-reoxygenation was characterized by phase changes of the corticosterone concentration in rat blood, which corresponded to the changes in energy metabolism as well as in pro- and antioxidant balance in rat liver mitochondria. It has been shown that short-term (1 day) hypoxia-reoxygenation (5% O2 in the gas mixture) led to an increase in the blood corticosterone concentration and a significant activation of oxidative processes and energy metabolism in rat liver mitochondria, the intensity of which was reduced to 3rd day.

[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.

Effect of potential-dependent potassium uptake on production of reactive oxygen species in rat brain mitochondria.

The effect of potential-dependent potassium uptake on reactive oxygen species (ROS) generation in mitochondria of rat brain was studied. It was found that the effect of K+ uptake on ROS production in the brain mitochondria under steady-state conditions (state 4) was determined by potassium-dependent changes in the membrane potential of the mitochondria (ΔΨm). At K+ concentrations within the range of 0-120 mM, an increase in the initial rate of K(+)-uptake into the matrix resulted in a decrease in the steady-state rate of ROS generation due to the K(+)-induced depolarization of the mitochondrial membrane.

Tissue oxygenation and mitochondrial respiration under different modes of intermittent hypoxia.

We compared the results of five modes of intermittent hypoxia training (IHT) on gastrocnemius muscle Po2 and heart and liver mitochondrial respiration in rats. Minutes of hypoxia, %O2, and recovery minutes on air in each mode were: 1) 5, 12%, 5; 2) 15, 12%, 15; 3) 5, 12%, 15; 4) 5, 7%, 5; and 5) 5, 7%, 15. Mode 1 proved best in that Pmo2 dropped minimally at the end of every hypoxic bout and recovered quickly after each bout.

[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.

Moderate hypoxia/hyperoxia attenuates acute hypoxia-induced oxidative damage and improves antioxidant defense in lung mitochondria.

A new mode of adaptive training was explored, which combines periods of hypoxia and hyperoxia (H/H) and is characterized by upregulation of adaptive ROS signals compared to classical intermittent hypoxic training. The purpose of this study was to determine the influence of repetitive moderate sessions of hypoxia and hyperoxia on pro-/antioxidant homeostasis in lung mitochondria of rats exposed to acute severe hypoxia. It was shown that H/H pretreatment [5 cycles of 5 min hypoxia (10% O2 in N2) alternated with 5 min hyperoxia (30% O2 in N2) daily for two weeks] reduced the acute hypoxia-induced basal and stimulated in vitro lipid peroxidation, increased the GSH/GSSG ratio, and decreased the GSSG content.

[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.

HIF-3α mRNA expression changes in different tissues and their role in adaptation to intermittent hypoxia and physical exercise.

The role of HIF-3α in response to intermittent hypoxia and physical exercise was investigated in Fisher rats using reverse transcription, real-time PCR and RNA interference. Under acute hypoxia (12% O(2), 2h), the level of HIF-1α, HIF-2α, and HIF-1β mRNA did not significantly change in the heart, lung, kidney and muscle tissues, but HIF-3α mRNA expression was strongly elevated in all tissues investigated. Five weeks of intermittent hypoxic training (IHT) led to an increase of HIF-3α mRNA in all studied tissues, but under the influence of acute hypoxia after IHT, the expression of HIF-3α mRNA did not increase in all tissues excluding skeletal muscle.

The effect of intermittent hypoxic training on lung and heart tissues of healthy rats.

Introduction: Recently, particular attention has been focused on the problem of the beneficial influence of intermittent hypoxia (IH) on the human organism. However, knowledge regarding the negative effects of intermittent hypoxic training (IHT) on cellular adaptive mechanisms remains limited. The aim of the present study was to investigate: 1) lung and heart ultrastructural changes under IHT; and 2) the adequateness of morphological and morphometric methods to determine the constructive and destructive displays of hypoxia.

Cytochrome C as an amplifier of ROS release in mitochondria.

The influence of exogenous cytochrome c on reactive oxygen species (ROS) formation and its dependence on mitochondrial permeability transition pore (MPTP) opening is studied in rat liver mitochondria. Fluorescent probe dichlorofluorescein (DCF) was used. It was shown that MPTP activation by increasing concentrations of Ca2+ in the medium results in the increase in mitochondrial ROS production and oxygen consumption, but the decrease in matrix calcium retention, dependent on the amount of added Ca2+.

[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.

[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.