Stepwise Cerebral Ischemia Causes Disturbances in Mitochondrial Respiration of Neurons in the Cerebral Cortex of Rats

Objectives: To conduct a comparative analysis of respiration of mitochondria of brain homogenates of rats with stepwise subtotal cerebral ischemia with different duration between ligations of both common carotid arteries. Methods: The experiments were performed on 24 male mongrel white rats weighing 260 ±20 g. Cerebral ischemia (CI) was simulated under intravenous thiopental anesthesia (40-50 mg/kg). The control group consisted of falsely operated rats of similar sex and weight. To study mitochondrial respiration, the brain was extracted in the cold (0-4°C), dried with filter paper, weighed and homogenized in an isolation medium containing 0.32 M sucrose, 10 mM Tris-HCl, 1 mM EDTA, pH 7.4 (in a ratio of 1:10), using Potter-Evelheim homogenizer with Teflon pestle according to the modified method. To prevent systematic measurement errors, brain samples from the compared control and experimental groups of animals were studied under the same conditions. Results: Stepwise SCI with an interval of 1 and 3 days between bandages of both OCA leads to damage to the neurons of the parietal cortex and hippocampus of rats, which manifests itself in a decrease in their size, deformation of the pericaryons, an increase in the number of shrunken neurons and shadow cells. The most pronounced changes were observed in the subgroup with an interval between dressings of 1 day. These changes were similar to the changes in SCI (p>0.05), except for the absence of cells with pericellular edema in the hippocampus and a smaller number of them in the parietal cortex. SCI with an interval between WASP dressings of 7 days, on the contrary, it is manifested by less pronounced histological changes, especially in the hippocampus. Conclusion: In cerebral ischemia, damage to the inner mitochondrial membrane occurs due to activation of free radical oxidation processes. Damage to the inner mitochondrial membrane, in turn, leads to an increase in its permeability and a decrease in the level of the proton gradient due to the transition of protons along the concentration gradient through the resulting nonspecific pores into the mitochondrial matrix. As a result, the efficiency of ATP synthesis decreases, and more substrates and oxygen are required to maintain the intermembrane potential under these conditions.

CHARACTERISTIC OF FREE-RADICAL DAMAGE AND ANTIOXIDANT PROTECTION STATE IN PATIENTS WITH CHRONIC KIDNEY DISEASE AGAINST A BACKGROUND OF MALABSORPTION SYNDROME

Oxidation processes play an important role in damage of the renal structures, especiallyagainst a background of other serious pathologies, in particular, malabsorptionsyndrome.The study of the mechanisms of mutual aggravation and progression of kidneydamage against a background of malabsorption is a very urgent problem of the presenttime.Purpose - to investigate the state of free radical oxidation of lipids, proteins andantioxidant defense in patients with chronic kidney disease of different ages withoxaluria against a background of malabsorption syndrome.Material and methods. 98 patients with chronic kidney disease of the I-II stages(pyelonephritis) with the presence of oxaluria against a background of malabsorptionsyndrome of different age were examined.The age of the patients under examination was32 - 64. All patients underwent a study of the system of free radical oxidation of lipidsand proteins.Results. chronic kidney disease with the presence of oxaluria is accompanied by asignificant increase in the blood content of free radical oxidation products, namelyaldehyde and ketone dinitrophenylhydrazones, especially of a neutral nature,malondialdehyde, as well as a significant decrease in the indicators of the antioxidantdefense system, which manifested itself to a greater extent in patients with older age.groups.Conclusion. An essential factor in the development and progression of chronic kidneydisease with the presence of oxaluria against a background of malabsorption syndromeis an increase in the intensity of free radical oxidation of lipids and proteins (mainly dueto aldehyde and ketondinitrophenylhydrazones of a neutral nature).

Relationship between indicators of insulin resistance and oxidative balancein adolescents with androgen deficiency

The purpose of the work was to study the relationship between the indicators of insulin resistance (IR), free radical oxidation products (FRO) levels, and the antioxidant system activity in adolescents with androgen deficiency (AD).Materials and methods. 58 adolescents 13­—18 years old with AD were examined. Serum levels of total testosterone, glucose, insulin, tiobarbituric acid active compounds (TBA), carbonylated proteins (CB), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) activity were determined. The HOMA index and the coefficient of oxidative stress were calculated.Results and discussion. In the group of adolescents with AD without IR, an inverse correlation was found between the HOMA index and CAT activity. CAT activity negatively correlated with CB content and glucose concentration. In addition, an inverse relationship was found between the activity of GPO and SOD. IR indices indirectly, through feedback with the activity of CAT, influence to the formation of conditions for inhibition/activation of FRO of proteins.IR was revealed in 37.9 % of the examined adolescents with AD. Direct relationship was recorded between IR indicators and markers of oxidative stress, as well as between testosterone levels and GPx activity in the group of these patients. Direct correlation between the coefficient of oxidative stress and the content of TBA-­active compounds indicates the formation of oxidative stress due to the activation of lipid peroxidation. Reduced testosterone levels in adolescents with AD inhibits an increase in GPx activity and prevents compensation for excessive intensity of free radical processes. Conclusion. The results indicate that adolescents with AD have a close relationship between the processes of carbohydrate metabolism, FRO, and antioxidant protection.In adolescents with AD without IR, a balancebetween the studied parameterswas found.The formation of IR in adolescents with AD shifts the equilibrium of the oxidative balance towards the activation of FRO processes. Decreased testosterone levels in adolescents with AD do not maintain the body’s antioxidant status within normal limits.

Some indicators of free radical oxidation and antioxidant protection in the erythrocytes of former athletes

Objective: to study the main indicators of free radical oxidation and antioxidant protection in the erythrocytes of former athletes, depending on the period of termination of sports.Materials and methods: 24 former male athletes aged 19–29 years were examined, who were divided into 2 groups of 12 people each (1st group — former athletes who stopped training for up to 2 years; 2nd — over 2 years). The control group consisted of 15 practically healthy untrained student volunteers of the same age. In erythrocytes, spectrophotometrically (spectrophotometer Shimadzu 1240, Japan), the activity of antioxidant enzymes was determined: superoxide dismutase (SOD) (K.F. 1.15.1.1) — by inhibiting the reduction of nitro blue tetrazolium by superoxide anion radical at λ = 540 nm, after preliminary processing of erythrocytes by the method of Dubinina E.E. and others [8]; catalase (K.F. 1.11.1.6) — according to the rate of utilization of hydrogen peroxide at λ = 260 nm; glutathione peroxidase (HP) (KF 1.11.1.9) — by the change in the content of reduced glutathione in samples before and after incubation of the substrate with dithiobis-nitrobenzoic acid at λ = 412 nm; glutathione reductase (GR) (K.F. 1.6.4.2) — according to the catalytic NADPH ∙ H+-dependent transformation of the oxidized form of glutathione into the reduced form, the intensity of which was estimated by the rate of decrease in the extinction of samples at λ = 340 nm, at which the NADPH H+ solution has a maximum light absorption (Warburg test).Results: the direction of the shifts in the state of the oxidative balance was established depending on the period of detraining. A significantly lower value of the total antioxidant activity was revealed in the former athletes of the 1st group. This phenomenon is probably associated with a decrease in the efficiency of the enzymatic link of the antioxidant defense in the absence of regular physical exertion, and, as a consequence, an increased consumption of non-enzymatic antioxidants. It was found that the early post-sports period is characterized by significantly lower, in comparison with the control group, the values of the activity of the first-order enzymes (superoxide dismutase) against the background of the increased activity of the second-order enzymes (catalase).Conclusions: the obtained data can be recommended for monitoring the state of athletes who stopped playing sports and taken into account when prescribing rehabilitation measures for the corresponding contingent.

Rhaponticum uniflorum and Serratula centauroides Extracts Attenuate Emotional Injury in Acute and Chronic Emotional Stress

In modern life, the use of plant stress-protectors has taken on particular significance due to the wide distribution of neurosis-like and neurotic diseases caused by neuroendocrine-immune system imbalance. Special attention has been paid to the plants containing ecdysteroids, i.e., hormone-like bioactive substances with high adaptogenic activity. The article deals with the study of bioactivity of two plant extracts as Rhaponticum uniflorum (L.) DC. and Serratula centauroides L. with a high content of ecdysteroids and phenolic compounds. The models of acute and chronic emotional stress in white rats were used to estimate the stress-protective activity of R. uniflorum and S. centauroides extracts. Both extracts showed the stress-protective effect via inhibiting the development of signs induced by single and long-term effects of stress factors. In acute stress, the development of Selye's triad signs was less pronounced against the background of the plant remedies introduction. In chronic stress, the extracts prevented the development of anxiety-depressive syndrome. Besides, R. uniflorum and S. centauroides extracts banned the development of stress-induced injuries in the brain cortex and had a neuroprotective effect on ischemia against chronic stress. The stress-protective effects of both plant extracts were based on a decrease of hyperactivation of the central stress-promoting systems (sympathoadrenal, hypothalamic-pituitary-adrenal) due to their GABA-mimetic effects. Peripheral mechanisms were connected with the inhibition of free radical oxidation processes and with an increase in the endogenous antioxidant system activity. Thus, R. uniflorum and S. centauroides extracts have a high potential to increase non-specific body resistance against acute and chronic emotional stress effects.

Pathophysiological bases of maladjustment formation in high mountains and polar zones

The pathophysiological features of the development of maladjustment under mountain-cold conditions as a manifestation of the syndrome of mutual burdening are considered. In this study, contents of various literary sources, characterizing a persons resistance to the effects of a complex of factors under high mountains and polar zones conditions, were analyzed. With the simultaneous exposure to hypoxia and hypothermia from a pathophysiological point of view, intersecting links of terminological paths, often having diametrically opposite dynamics of changes in the characterized concepts, will be significant. Thus, in the terminological mitochondrial pathway of energy metabolism, uncoupling proteins are present, which, to increase the resistance to hypothermia, should be activated to switch the energy metabolism to predominantly use fatty acids. However, hypoxic conditions should be suppressed to maintain the level of adenosine triphosphate acid available for cells. In the terminological tract of compensatory reactions in response to hypoxemia, the volume of pulmonary ventilation is released, which must increase to improve tolerance to hypoxia, which, under mountain-cold conditions, increased heat loss and promote the deterioration of the condition, i.e., tolerance to low temperatures. Under hypoxic and hypothermic conditions, a synergistic interaction can form, which can be manifested by the development of a syndrome of mutual burdening, which will result in a significant decrease in the functional capabilities of the body, result, and productivity. Maladjustment to mountain cold, with maximum probability, will manifest as disorders of the central nervous system, decreased physical performance, depletion of the functional and regulatory reserves of the body, functional immunodeficiency, decreased regenerative potential, and development of endogenous intoxication. With a high degree of probability, a significant synergistic interaction of hypoxia and hypothermia can be found in relation to the indicators of pulmonary ventilation, blood gases (hypercapnia), acidbase balance (gas alkalosis and lactic acidosis), heart rate (tachycardia), blood pressure (hypotension), central venous pressure (increase), blood viscosity (increase) and its coagulability (hypercoagulation), peroxide and free radical oxidation (activation), and protein catabolism (increase). These changes will negatively affect the functional state of specialists performing complex professional tasks in polar latitudes.

Effects of His-Phe-Arg-Trp-Pro-Gly-Pro peptide on free-radical oxidation processes in conditions of chronic restraint stress

Studying the effects of regulatory peptides on the stress-induced shifts in the bodily processes is of great fundamental and applied significance. Currently, a wide range of peptide neurotropic drugs, affecting the stress response development, are used in medicine, and new promising molecules are being studied. The study was aimed to assess the effects of the adrenocorticotropic hormone (ACTH) synthetic analog, ACTH(6-9)-Pro-Gly-Pro, administered at a dose of 5, 50 and 500 μg/kg, on the free-radical oxidation processes in Wistar rats, subjected to chronic restraint stress (CRS) during two weeks. Serum levels of 8-oxo-2'-deoxyguanosine (8-OHdG) and superoxide dismutase 3 (SOD3) were assessed by enzyme immunoassay, and the levels of thiobarbituric acid reactive substances (TBARS) were assessed by fluorimetric method. CRS lead to the significant increase in the 8-OHdG levels by 18.4% (p = 0.01) and the decrease in the SOD3 levels by 14.3% (p = 0.01), however, it had no effect on the levels of TBARS. ACTH(6-9)-Pro-Gly-Pro, administered at a dose of 5 and 50 μg/kg, significantly decreased the levels of 8-OHdG by 19.8% (p = 0.03) and 30% (p = 0.001), respectively. Thus, it was found that CRS resulted in oxidative stress in animals. ACTH(6-9)-Pro-Gly-Pro administration at a dose of 5 and 50 μg/kg inhibits the stress-induced free-radical oxidation processes.

Вплив цинку на метаболічні процеси в нормі та при патології

Zinc belongs to the independent human trace elements. Its biological role is taken into account with the activity of attracting endocrine secretion. As a component of some enzymes, zinc affects the processes of reproduction, live and carbohydrate metabolism. Zinc is an important trace element with a variety of biological functions, which is involved in cell growth, apoptosis and metabolism, as well as in the regulation of endocrine, immune and neuronal functions. At the cellular level, zinc stimulates the formation of polysomes, inhibits free radical oxidation, which is catalyzed by iron. The important role of zinc in nucleic metabolism, transcription processes, stabilization of nucleic acids, proteins and especially components of biological membranes. Zinc plays an important role in skeletal development. Zinc accelerates the synthesis of collagen in wounds, has a stabilizing effect on cytoplasmic membranes, and prevents the release of hydrolytic enzymes. In mitochondria, zinc inhibits the transport of electrons in the respiratory chain. This property is realized in sperm, where there is a lot of zinc and there is low respiratory activity of mitochondria. Zinc is necessary for the development of brain tissue. Zincergic neurons are found in the cerebral cortex. Zinc has been shown to play an important role in signal transduction by modulating excitatory and inhibitory cellular receptors and intracellular signaling proteins. Zinc has a special effect on the development and course of many diseases, such as Down syndrome, alcoholism, angina, dysmenorrhea, atherosclerosis and more.

PSXI-25 Antioxidant system characteristics in Saanen goats depending on age

Goat husbandry is a relevant and significant research topic. The goat age is possible to reach 15–18 years and it is important to study not only performance processes, but also to evaluate age-related changes. The purpose of this study was to evaluate antioxidant system characteristics in Saanen goats depending on age. The experiment was conducted in the north-western region of Russian Federation, the Leningrad Region. The five experimental groups included 30 Saanen goats each, selected using matched pairs method. 1st group included 1 year old goats, 2nd group included 2-year-old goats, 3rd group included 3-year-old goats, 4th group included 4-year-old goats and 5th group included 5-year-old animals. The blood samples were taken once –during the summer season. The blood levels of lipid peroxygenation markers (malondialdehyde, dienketone and conjugated dienes) and superoxide dismutase and catalase activity were assessed by standard methods. Results presented as mean±standard error of the mean. Student’s t-test was used after proving normal distribution. Level of significance is labeled as P < 0.05. The results are displayed in table 1 and 2. After analyzing the received data of antioxidant system characteristics there were revealed high intensity of free-radical oxidation in aged 4–5-year-old goats. This is explained by oxidative stress development. Noticeably that anti-oxidizing enzymes activity was reduced by the age of 5 years – the possible reason for lacking compensation of developed oxidative stress. By the age of 4 activity of anti-oxidizing enzymes was elevated marking the compensation stage of oxidative stress, this elevation is statistically significant. Consequently, these data allow taking into consideration exogenous anti-oxidizing agents administration in 5 years and older goats in order to reduce oxidative stress.