[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%. During the incubation with doxorubicin, the number of live cells decreased by 30.4% and the number of necrotic cells increased by 30.4% relative to control. Coadministration of doxorubicin and curcumin led to augmented cell viability by 8%, while the number of necrotic cells reduced by 8% compared with the use of doxorubicin only. In assessing the parameters of mitochondrial respiration in rats that received injections of doxorubicin active breathing index (V(3)) fell by 43.8%, the oxidation rate of the contingency of phosphorylation (V(3)/V(4)(ATp)) decreased by 47% and phosphorylation efficiency index (ADP/O) also declined by 31.7% respectively compared with the control. The combined use of doxorubicin and curcumin improved the indicators of mitochondrial respiration compared to using only doxorubicin: V(3) raised by 25%, V(3)/V(4)(ATP)by 18% and ADP/O by 12% respectively.

[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. Long- term hypoxia--reoxygenation (7-14th days) led to the gradual depletion of the organism adaptive capabilities, as evidenced by a significant decline in the blood corticosterone concentration, an increase in the content of secondary products of lipid peroxidation, an imbalance in pro- and antioxidant reactions and reduction of energy capacity in liver cells mitochondria. It has been shown that the glutathione peroxidase protein expression and enzymatic activity increased constantly during the whole experimental period and correlated positively with the level of H2O2. The amount of Mn-SOD protein as well as it's enzymatic activity was lower in the first seven days of experiment, and it was increased in consequent days up to the control level on 14thday. Increased activity of glutathione peroxidase, glutathione reductase and NADP+⁺dependent isocitrate dehydrogenase during prolonged hypoxia - eoxygenation indicates that glutathione- and NADPH-generating enzymes, were actively involved in the antioxidant protect.

[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 2.9 ± 0.8 cu, so it decreased by 20% compared to control--3.6 ± 0.7 cu (P < 0.05). The level of expression of the HIF target gene PDK-1 also significantly decreased (4 times). During the incubation with doxorubicin, the number of live cells decreased by 50.4% relative to control. And after using doxorubicin and curcumin together, the percentage of dead cells decreased by 7,7 compared to doxorubicin only. Doxorubicin intoxication led to a significant increase in the secondary products of lipid peroxidation (TBARS) in cardiomyocytes by 3.6 times and hydrogen peroxide by 64%. Prolonged incubation with doxorubicin reduced the enzymatic activity of Mn-SOD by 32%, while catalase activity increased by 72% compared to control. Adding of curcumin to the cardiomyocyte cell culture contributed to increasing of the Mn-SOD activity by 14%, catalase--by 23%. The level of TBARS increased by 1,4 times compared with the control, and the level of H2O2 increased by 20%. The joint use of doxorubicin and curcumin resulted in a significant reduction of free radical oxidation unlike effect of doxorubicin per se. Specifically, there was lessening of TBARS and H2O2 (at 56.7 and 18.4% respectively), while decreasing of the catalase hyperactivation (19%) and rising of the Mn-SOD activity (35%).

[The effect of uridine on the endurance of animals with different resistance to physical stress: the role of mitochondrial ATP-dependent potassium channel].

The effect of a metabolic precursor of natural activator of mitochondrial ATP-dependent potassium channel (mitochondrial K+(ATP))--uridine on animal's endurance to physical stress was studied. The endurance was determined by recording the time period during which the rat loaded with a plummet of 20% of body weight can swim until physical exhaustion at 32 degrees C. It was found that highly resistant animals swam until exhaustion for 7.40 ± 0.35 min, whereas low resistant rats hold out 2.07 ± 0.10 min only. The injection of uridine influenced the swimming time of the animals, increasing it twofold in low-resistant rats. The effect of uridine was decreased by injection of inhibitors of mitochondrial K+(ATP) channel. It was found that the injection of uridine into low resistant rats increased the rate of potassium transport in mitochondria isolated from liver of these rats, and inhibitors of the channel prevent the channel activating effect of uridine. The role of mitochondrial K+(ATP) cannel in the formation of animal's resistance to physical stress and protection of tissues from hypoxia is discussed.

[Antimicrobial properties of antiseptic composite with prolonged action].

Antimicrobial properties of a composite based on decamethoxine and modified polysaccharides (carboxymethylamylum, oxyethyl-cellulose) were studied. The composite was shown to have high antimicrobial activity against grampositive and gramnegative bacteria under different conditions of the experiment.

Effects of different modes of interval hypoxic training on morphological characteristics and antioxidant status of heart and lung tissues.

The effects of various modes of interval hypoxic training differing by the intensity and duration of hypoxic exposure on the morphology and antioxidant status of the heart and lung tissues were studied. Interval hypoxic training mode with more severe, but shorter hypoxic component led to the prooxidant/antioxidant imbalance in the myocardial and lung tissues, which was paralleled by significant disorders in their morphology and function. Moderate hypoxic exposure of different duration promoted the maintenance of optimum antioxidant homeostasis and development of compensatory adaptive changes in tissue structure.

Effect of intermittent hypoxia on pro- and antioxidant balance in rat heart during high-intensity chronic exercise.

The purpose of the present study was to elucidate the influence of sessions of intermittent hypoxic training (IHT) alone and in combination with high-intensity chronic exercise on lipid peroxidation and antioxidative defense system in rat heart. High-intensity chronic exercise was performed as swimming training with load that corresponded to ~ 75% VO2max(30 min/day, 5 days/wk, for 4 wk). IHT consisted of repeated episodes of hypoxia (12% O2, 15 min), interrupted by equal periods of recovery (5 sessions/day, for 2wk). Sessions of IHT were applied during the first two weeks and during the last two weeks of chronic exercise. It was shown that long-term training was accompanied by the accumulation of thiobarbituric acid reactive substances (TBARS) in myocardium. IHT attenuated the increase in TBARS content caused by high-intensity chronic exercise and it enhanced myocardial reduced glutathione concentration, activities of superoxide dismutase, catalase, and glutathione peroxidase in comparison with trained animals only. No significant changes were found in glutathione reductase, glucose-6-phosphate dehydrogenase activities. Our results suggest that intermittent hypoxic stimuli may induce a state of preconditioning that protects the heart from oxidative stress evoked by high-intensity chronic exercise.

Corrections of prooxidant-antioxidant homeostasis of organism under hypoxia of different genesis by yackton, a new pharmacological preparation.

The aim of the present work was to study the antioxidant activity of the new derivative of succinic acid-succinate mono[(2-dimethyl-amino) ethyl ether] of succinic acid (yackton) under conditions of hypoxic and hemic hypoxia as well as to examine in vitro the antiradical activity of this preparation. Hypoxia in the rats was modelled by: (i) allowing the rats to breath a gas mixture with 7% O2 and 93% N2 for 30 minutes (hypoxic hypoxia), and (ii) injecting the rats sodium nitrite subcutaneously in a dose of 60 mg/kg body weight (hemic hypoxia). Yackton was injected intraperitoneally to both groups 30 minutes before the extreme influence in a dose of 140 mg/kg body weight. Then in homogenates and in post-mitochondrial fractions of liver, heart, lungs, brain we studied the content of secondary products of lipid peroxidation (LPO), activity of antioxidant enzymes superoxide dismutase (SOD) and catalase, and the activity of enzymes responsible for the maintenance of reduced glutathione (GSH) glutathione reductase (GR-ase) and glutathione peroxidase (GP-ase). In vitro studies were made on the antiradical activity of yackton in reaction with the stable radical diphenylpicrylhydrazine (DPPH) as well as on the reaction velocity of the preparation with DPPH, and its period of semi-transformation in a non-radical form. It was shown that yackton treatment before hypoxic and hemic hypoxia decreased lipid peroxidation (LPO) level and increased SOD activity. After the yackton injection the state of glutathione system was normalized in comparison with its state at hypoxic and hemic hypoxia. Yackton had no antiradical properties in vitro. We concluded that yackton promotes optimization of prooxidant-antioxidant homeostasis of the organism under the hemic and hypoxic hypoxia acting as antioxidant of a non-direct action.

[Reaction of lysosomes of neutrophilic leukocytes and systems of plasma hemostasis under conditions of immobilization stress in hypothyroidism]. / Reaktsiia lizosom neitrofil'nykh leikotsytiv i system hemostazu plazmy za umov immobilizashchinogo stresu pri hipotyreoïdyzmi.

The reaction of haemostatic system under conditions of the oppression of the thyroid system as the result of the immobilization have been studied in the experiments on rabbits. It has been revealed that the thyroid hormones take part in the regulation of the blood coagulation, fibrinolysis and kininogenesis independently and under stress-syndrome development by the activation of lysosomal apparatus of neutrophilic leukocytes of peripheral blood.

[The pathogenesis and results of the surgical treatment of stress urinary incontinence in women]. / Patogenez i rezul'taty operativnogo lecheniia stressovogo nederzhaniia mochi u zhenshchin.

The paper presents the incidence rate (3-19.6%) of stress-induced enuresis (SIE) in females. The impact of birth injuries, obstetric instrumentation and heavy physical work resulting in the impairments of the sphincter-detrusor system of the bladder and the musculature of the pelvic bottom on the pathogenesis of SIE is indicated. As a result the bottom of the bladder, the posterior walls of the neck and urethra moved backward to form an obtuse angle with an anterior wall of the urethra that was roentgenologically evidenced as vesiculation. In this line the angle between the anterior and posterior walls of the urethra and neck became more obtuse with no contact upon contractility of their muscles which caused the stress-induced escape of urine. To eliminate vesiculation and enuresis, the authors used successfully the technique of urethral angulation by the duplication formed by the anterior vaginal wall over the cervix and urethra followed by their fixation to the posterior surface of the pubic area on one side and free skin graft on the other. Hebell-Schteckel's technique was a prototype for the method proposed. A total of 156 females with stages II and III SIE were successfully operated on. The results of 1-15 year follow-ups were good and satisfactory in 97 (89.9%) of 109 females. The relapses were more common in the females who had a repeated delivery or were engaged in heavy physical work as well as in two persons operated on in the menopause.