INTENSITY OF FREE RADICAL PROCESSES IN THE POSTNUCLEAR FRACTION OF RAT KIDNEYS UNDER INFLUENCE OF LASER IRRADIATION AND ω-3 POLYUNSATURATED FATTY ACIDS

Introduction. The effect of laser irradiation on the body can lead to local tissue damage, which will be accompanied by changes in biochemical processes that occur in the kidneys. The direction of these changes is completely unclear, so the study of free radical oxidation of lipids and proteins as the main markers of oxidative stress in the body and their correction by ω-3 polyunsaturated fatty acids (PUFA) remains relevant. Aim. To evaluate the intensity of lipid peroxidation and oxidative modification of proteins in the postnuclear fraction of rat kidneys under the action of laser irradiation and additional administration of ω-3 PUFA. Methods. The studies used white outbred rats, which were irradiated daily for 4 minutes with a laser diode with a wavelength of 650 nm, power of 50 mW in the abdominal cavity at a distance of 10 cm from the skin surface. The state of lipid peroxidation (LPO) was determined by the level of primary, secondary and final products. The intensity of oxidative modification of proteins (OMP) was evaluated by the level of carbonyl derivatives and protein SH-groups. To correct the prooxidant state, the animals were additionally injected with ω-3 PUFA. Results. Low-intensity laser irradiation has a destructive effect on the cell membranes of the kidneys, which is expressed by an increase in primary, secondary and final products of LPO in phospholipid extracts and an increase in the intensity of OMP. The introduction of ω-3 PUFAs reduces free radical processes in the kidneys of irradiated rats, but this effect depends on the scheme of their introduction. ω-3 PUFAs do not show antioxidant effect under the conditions of their introduction after laser irradiation. Daily administration of ω-3 PUFA two hours before irradiation shows a slight antioxidant effect only in the initial stages of irradiation. Preliminary seven-day administration of ω-3 PUFA before laser irradiation is the most effective, as it helps to reduce free radical processes. Conclusion. It is established that ω-3 PUFAs are able to have a corrective effect on the action of low-intensity laser irradiation, which depends on the scheme of their introduction. The highest antioxidant effect is observed in groups of animals to which ω-3 PUFA was previously administered before the action of laser irradiation.

Regulation of free radical processes in healthy volunteers during experimental hyperthermia and in patients with coronary artery disease during summer heat waves

Background. In view of the worsening forecast for global temperature rise worldwide, it seems relevant to study the effects of abnormal heat waves on systemic regulatory processes in people with chronic diseases, in particular coronary artery disease (CAD).Aims. This study aimed to investigate the effect of hyperthermia on oxidative stress parameters in patients with various severity of CAD and in healthy subjects.Materials and methods. We studied the level of malonic dialdehyde (MDA) and the activity of Cu,Zn-containing superoxide dismutase (Cu,Zn-SOD) in healthy subjects under conditions of 30-day long simulated hyperthermia and in patients with different severity of CAD after the summer heat wavesResults. We revealed signs of oxidative stress in healthy volunteers during model hyperthermia that manifested as an increase in content of MDA in blood plasma. At the same time we observed increasing activity of Cu,Zn-SOD in erythrocytes that utilizes reactive oxygen species. The increase of Cu,Zn-SOD activity started with a certain latency what also can be explained by de novo enzyme biosynthesis induction. We also studied oxidative stress parameters in patients at high and moderate cardiovascular risk according to the SCORE risk chart with uncomplicated CAD course and in patients with complicated CAD with severe coronary damage according to angiography during the summer heat waves. We observed accumulation of MDA in blood plasma and increasing activity of erythrocyte Cu,Zn-SOD in patients with uncomplicated CAD. At the same time we noted that accumulation of MDA in blood plasma was not followed by any increase in activity of red blood cell Cu,Zn-SOD in patients with severe complicated CAD. This fact indicates dysregulation of free radical processes in patients with severe course of CAD during the heat waves.Conclusions. The dysregulation of free-radical processes in patients with a severe clinical course of CAD has been revealed.

Molecular and cellular mechanisms of ultraviolet corneal crosslinking

In the presented mainly experimental work, the regularities and mechanisms of ultrastructural transformation and changes in corneal metabolism under ultraviolet exposure are established. High-quality saturation of the stroma with riboflavin is necessary to perform safe and effective UV crosslinking of the cornea, which can be achieved mainly due to a sufficient area of de-epithelization (at least 8-9 mm). It was found that UV crosslinking of the cornea with the use of developed riboflavin solutions (Dextralink, Ribolink and Khitolink) as photosensitizers increases its strength properties associated with changes in the structural state of collagen fibrils. It is proved that the riboflavin-UV effect on the optical shell of the eyeball is caused by a short-term local increase in free radical processes, a decrease in the overall antioxidant status, and the absence of necrotic and significant inflammatory reactions. It is shown that the lack of riboflavin in the stroma forms a cascade of pathomorphological events of an irreversible nature, leading to the loss of the native structure of the cornea. On the basis of the conducted studies, the necessity of a differentiated approach to the use of riboflavin-containing solutions during ultraviolet crosslinking of the cornea is justified. Key words: ultraviolet corneal crosslinking, molecular-cellular mechanisms, photosensitizers, riboflavin.

Pathogenetic rationale for using an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase and an antioxidant coenzyme Q10 in the treatment and prevention of cardiovascular disease

The review discusses atherosclerosis-related mechanisms of car-diovascular disease development, as well as the optimization of their prevention and treatment methods. Recent experimental and clinical studies have shown the important role of vascular endothelium in the development and progression of atherosclerosis. Myocardial ischemia, activation of free-radical processes and impaired bioenergetics initiate a decrease in production of nitric oxide, which plays major vasodilator role. In this regard, the scientists is interested in the search for new drugs that can affect the main pathogenetic links of coronary artery disease. Statins are currently the drugs of choice. However, they are not always effective and have an ambiguous effect on oxidative potential of myocardial cells and endothelial function. Moreover, inhibition of mevalonic pathway for cholesterol synthesis is accompanied by a deficiency of coenzyme Q10, which is the central cellular antioxidant that protects phospholipids of cell membranes from free radicals. Rationale of using coenzyme Q10 in the complex treatment and secondary prev ention of cardiovascular diseases, including coronary artery di sease, is discussed.

ЕFFECT OF IRON AND NICKEL DITHIOCARBAMATES ON THE PROPERTIES OF MODIFIED POLYURETHANES

The effect of modifiers - nickel bis(N,N-dimethyldithiocarbamate) (DTC-Ni) and iron tris(N, N-dimethyldithiocarbamate) (DTC-Fe) depending on their content on the structural peculiarities of polyurethane matrix based on polyoxytetramethylene glycol-1000 4,4’-diphenylmethane diisocyanate and 1,4-butanediol has been studied. The method of IR spectroscopy according to the results of NH groups’, C = O- and COC fragments’ association has shown the structuring effect of modifiers due to the PU matrix coordination. The processes of photolysis occurred as a result of exposure of PU under the conditions of the climate chamber have been also studied by IR spectroscopy method. The influence of modifiers and their content on the modified polyurethanes density has been investigated. The planar structure of DTC-Ni has shown to contribute to the density increase of modified PU as the result of polymer chain coordination, while the spherical structure of DTC-Fe - causes a density decrease due to steric hindrances in the implementation of H-bonds. Modification of polyurethanes with both nickel bis (N, N-dimethyldithiocarbamate) and iron tris (N, N-dimethyldithiocarbamate) as well as UV irradiation and moisture under the conditions of the climatic chamber contribute to the increase of water absorption. Studies of the strength properties of modified polyurethanes in comparison with the matrix under the conditions of the climate chamber have established the photosensitizing effect of nickel and iron dithiocarbamates. By studying the mass of samples of PU-DTС-Fe/Ni after extraction with dimethylformamide in the Soxhlet apparatus it has been found an increase in the level of gel fraction (0.29 - 1.58%) with increasing the modifier content, which confirms the presence of a network structure of modified PU due to radical processes taking place during destruction with the modifier participation. The influence of alkaline and acidic media on the destruction level of both modified polyurethanes and their analogues depending on the modifier content under the influence of climatic chamber conditions has been studied. Comparative derivatographic studies in air of weight loss of modified polyurethanes have confirmed the structuring and thermostabilizing effect of DTC-Ni on the PU matrix due to the probable difficulty of oxygen diffusion to the polymer volume, while the spatial structure of PU-DTC-Fe reduces the thermal stability.

Strategies for the Synthesis of Selenocysteine Derivatives

β-Seleno-α-amino acids, known as selenocysteine (Sec) derivatives, have emerged as important targets because of their role in chemical biology, not only as part of selenoproteins with important redox properties, but also because of their activities as antivirals or metabolites effective in inhibiting carcinogenesis. In addition, there is a demand for this type of compounds due to their use in native chemical ligation to construct large peptides. Therefore, this review summarizes the various synthetic methods that have been published to construct Sec derivatives. Most of them involve the generation of the C-Se bond by nucleophilic substitution reactions, but other reactions such as radical or multicomponent strategies are also reported. Of particular importance is the Se-Michael addition of Se-nucleophiles to chiral bicyclic dehydroalanines, in which the stereogenic centre is generated under complete stereocontrol. 1 Introduction 2 Previously reviewed synthesis of Sec 3 Retrosynthesis of Sec derivatives 4 Sec derivatives by nucleophilic substitutions 5 Sec derivatives by radical processes 6 Sec derivatives by 1,4-conjugate additions