Цель. Оценить противоопухолевый эффект глюконатов марганца, меди и цинка на модели миеломы Sp2/0 Ag14 у линейных мышей BALB/c. Материал и методы. Мыши линии BALB/c с трансплантированной миеломой Sр 2/0 Аg14 получали перорально в течение трех недель глюконаты марганца, меди и цинка, синтезированные в Уфимском институте химии УФИЦ РАН, препаратом сравнения служил циклофосфамид. На 22 день проводили гистологические исследования органов и опухолевых образований, а также оценивали противоопухолевый эффект, рассчитывая показатели опухолевой регрессии: торможение прироста массы тела (ТПМ), торможение развития асцита (ТРА) и через 3 месяца — увеличение продолжительности жизни (УПЖ). Результаты. Гистологические исследования показали отсутствие солидных опухолевых образований в группах мышей после трехнедельной терапии глюконатами металлов. В тканях органов существенных изменений по сравнению с контрольной группой интактных животных выявлено не было. В группе животных без лечения зарегистрировано образование узловатой опухоли с выраженной сетью сосудистых структур, в которых после терапии циклофосфамидом обнаружен венозный застой, приводящий к скоплению лимфоидных клеток в стенках ячеек опухоли. Показатели ТПМ, ТРА и УПЖ в группе с препаратом сравнения циклофосфамид имели значения: 28,8 %, 29,4 % и 153,5 %, которые оказались близкими к показателям в группе с терапией глюконатом меди. Глюконаты марганца и цинка показали более высокую эффективность, превышающую эффективность препарата сравнения на 30-40 %. Заключение. Введение в течение трех недель глюконатов марганца, меди и цинка замедляет развитие опухолевого процесса у мышей BALB/c с миеломой Sp2/0 Ag14: на этапе забора материала солидных опухолевых образований не обнаружено, рост опухоли отмечен только после отмены препаратов. Результаты эксперимента подкреплены морфологическим контролем и статистическими расчетами с помощью программы «Statistica 10,0». Ингибирование роста опухоли (30-40 %) зарегистрировано по изменению массы тела, накопления асцита и продолжительности жизни.

The nature of the influence of the silicon atom on remote nitrogen and oxygen atoms in the molecules of 4-(dimethylamino)-1,1-diethylsilacyclopentan-3-ol and 2-(dimethylamino)-5-trimethylsilylcyclohexan-1-ol has been studied in the framework of the MO LCAO theory by the TPSS/cc-pVTZ, Hirshfeld and NBO analysis methods. Being more pronounced in the 4-(dimethylamino)-1,1-diethylsilacyclopentan-3-ol molecule, this effect is determined by the geometric parameters (endocyclic arrangement of the silicon atom) which favor the formation of MOs with a large Si contribution. According to the NBO analysis, the interaction between the orbitals of the Si–C5 bonds and the orbitals of the C3–N and C1–O bonds in the silacyclopentane fragment of the 4-(dimethylamino)-1,1-diethylsilacyclopentan-3-ol molecule has donor-acceptor nature. The calculated data are in qualitative agreement with the results of 1H and 29Si NMR spectroscopy.

The high proportion of iodine deficiency diseases in the structure of general morbidity determines the relevance of creating new nontoxic iodine-containing compounds and improving the processes of iodization of foods of mass consumption. In recent years, to solve this problem, a number of iodine-containing compounds based on natural polymers have been proposed, including pectin (iodinepectin), casein (iodine-casein), inulin (iodine-inulin). It seems promising to create iodine-containing conjugates for food industry not only based on natural polymers, which are not individual compounds, but also based on low-molecular plant metabolites that have a high potential for correcting public health. The attention of researchers is attracted, in particular, by the glycosides of Stevia rebaudiana, which have positively proven themselves in the food industry for many years. Current trends in the development of industrial production of iodine-fortified products also include requirements for the compatibility of iodine-containing concentrates with food industry technologies, especially in the formation of time-stable micro-heterogeneous aqueous dispersions. In connection with the above, the purpose of the research was to confirm the formation of an iodine conjugate with a low molecular weight metabolite of Stevia rebaudiana (glycoside rebaudioside A) by infrared (IR) spectroscopy; and to assess the resistance to sedimentation of its aqueous micro-heterogeneous dispersions (iodine-glycoside) comparatively with iodine compounds with natural plant polymeric carriers - pectin (iodine-pectin) and inulin (iodine-inulin) by the method of nanostructural analysis. Material and methods. The IR spectra of the compounds were recorded on a Fourier spectrometer. Measurement of particle sizes in dispersions of iodine-containing substances was carried out on a laser analyzer, wave length 375 nm, in a quartz cuvette (7 ml) after 0, 2, 4, 6, 10, 24, 72 and 144 h. To prepare dispersions, a weighed portion of iodine-pectin (105 mg) was mixed in 100 cm3 of water (600 rpm) at a temperature of 35-40 °C for 60-70 min, weighed portions of iodine-glycoside (120 mg) and iodine-inulin (49.7 mg) were dissolved in 100 cm3 of water at room temperature (23 °C) for 3-4 min. Results. An IR spectroscopy study of the interaction of iodine with rebaudioside A indicated the stabilization of molecular iodine by the functional groups of the glycoside, leading to the formation of a stable iodine-glycoside conjugate. Assessment of the aqueous dispersions of particles of this conjugate by nanostructural analysis showed that the substance iodine-glycoside formed a stable microheterogeneous dispersion with a particle diameter of about 300 nm, which didn't undergo sedimentation during the entire observation period (6 days). Aqueous dispersions of the iodine-inulin with a particle size of 10 nm were comparable with true solutions and remained also stable throughout the entire observation period. Particles of the iodine-containing compound iodine-pectin formed moderately stable aquatic dispersed systems, the time of complete sedimentation of which was 6-10 h. Conclusion. The study of the IR spectra of rebaudioside A and the synthesized sample iodine-glycoside made it possible to confirm the conclusion about the inclusion of iodine molecules in the structure of glycoside molecules. Micro-heterogeneous stable dispersions of this conjugate, as well as iodine-inulin substances, can be convenient concentrates for enriching milk with iodine. Rapid aggregation of particles of iodine-pectin substances in concentrates can prevent their uniform distribution in the target environment, which reduces the effectiveness of industrial technologies for iodine-fortified foods for the mass prevention of endemic goiter.

ВЛИЯНИЕ ГЛЮКОНАТОВ МАРГАНЦА, МЕДИ И ЦИНКА НА ФАГОЦИТАРНУЮ АКТИВНОСТЬ НЕЙТРОФИЛОВ ПЕРИФЕРИЧЕСКОЙ КРОВИ МЫШЕЙ

Background. The development of endogenous intoxication in the treatment of oncological pathology with cytostatic drugs complicates targeted therapy, so the search for correctors of these conditions is an actual task. Previously, we have shown in vivo the corrective effect of 3d-metal gluconates on the humoral link of immunity with the administration of the widely used cytostatic cyclophosphamide. It is of interest to evaluate the effect of 3d-metal gluconates on changes in leukocyte parameters of endogenous intoxication affected by cyclophosphamide. Aim. Evaluation of the effect of 3d-metal gluconates (Mn, Fe, Co, Cu, Zn) on the degree of endogenous intoxication in mice against the background of the cytostatic effect of cyclophosphamide. Material and methods. The experiment was carried out on white laboratory male mice weighing 2528 g, divided into 9 groups [1 intact animals, 2 administration of cyclophosphamide without treatment, 3 administration of cyclophosphamide and a comparison drug with an immunostimulating effect, 4 administration of cyclophosphamide and the comparison drug calcium gluconate, groups 59 administration of cyclophosphamide and gluconates of 3d-metals (MnGl, FeGl, CoGl , CuGl and ZnGl, respectively)], 12 individuals each, kept in the vivarium conditions on a standard diet. Endogenous intoxication was induced by a single injection of cyclophosphamide. 3d-metal gluconates (Mn, Fe, Co, Cu, Zn) and comparison drugs (glucosaminylmuramyl dipeptide in the form of Likopid, and calcium gluconate) were used to correct changes in the immune system. The administration of the drugs was started 24 hours after the administration of the cytostatic and then daily orally during 21 days. Blood sampling was performed on the 22nd day. The assessment of the degree of endogenous intoxication was carried out by determining the leukocyte indices: stress activity index, leukocyte intoxication index, nuclear index of the degree of endotoxicosis, and leukocyte shift index. Statistical processing of the results was performed using the Statistica 10.0 program. To calculate the significance of differences between groups, the nonparametric MannWhitney test was used. Changes were considered significant at p 0.05. Results. After the administration of cyclophosphamide in animals, a significant change in the leukocyte formula, which indicates an acute intoxication of the body, was observed: there was a decrease in the content of monocytes (3 times), segmented neutrophils (1.5 times), an increase in stab neutrophils (2 times), lymphocytes (1.1 times). The intake of 3d-metal gluconates led to the correction of leukocyte indices, the degree of which statistically significantly exceeded the degree of correction by the comparison drugs Licopid and Calcium gluconate (p 0.05), and for Zn (II) gluconate it was from 45 to 84%, for Mn (II) gluconate from 44 to 100%. Conclusion. Gluconates of 3d-metals reduce the degree of endogenous intoxication caused by cyclophosphamide, increase the reactivity of phagocytes and the regeneration rate of the leukocyte link. In terms of efficiency, 3d-metal gluconates can be arranged in the following order (according to metals): Mn ˃Zn ˃Cu ˃Co ˃Fe.

Mercury(II) oxide has been reacted with D-gluconic acid (Gl) in an aqueous solution at a molar ratio of the reagents equal to 1: 2 to obtain mercury complex Hg 2 (C 6 H 11 O 7 ) 2 (I). The product isolated has been studied by elemental analysis, molar conductivity, IR, electronic, and NMR spectroscopy, and X-ray diffraction. The data obtained indicate that the compound contains the binuclear cation (Hg 2 ) 2+ . It has been found that the complex has a chelate structure. Each mercury atom in I is connected with two oxygen atoms: one from the carbon atom of the carboxyl group and another from the hydroxyl group at the second carbon atom in the Gl molecule. Two gluconate ions in the complex have different configurations. Toxicity of I is ten times less than the toxicity of the starting mercury compound. Reacting Gl with the oxide of divalent mercury in an aqueous medium decreased he toxicity of the mercury compound due to its reduction to a formally monovalent state. The results can be useful for studying mercury detoxification and the application of Gl.

Aim. Evaluation of the effect of 3d-metal gluconates on complement-fixing function of immunoglobulin G and functional activity of complement. Methods. The study was conducted in vivo on 2.5-3 month-old white laboratory mice weighing 25-28 g with secondary immunodeficiency, which was induced by a single intraperitoneal injection of cyclophosphamide, as well as in vitro in a test system using sensitized sheep erythrocytes. Immunological studies were performed in intact animals, and before and after the administration of Mn, Co, Cu, and Zn gluconates to mice with induced immunodeficiency. The content of immunoglobulin G and its complexes with subcomponent of the complement first component C1q was determined in serum by ELISA using specific monoclonal antibodies. Results. Two-week oral administration of 3d-metal gluconates (Mn, Co, Cu, Zn) in a dose of 1/10 LD50 to immunodeficient mice was shown to cause a significant increase in the level of immunoglobulin G and its complexes with C1q. The greatest increase in concentration was observed with the introduction of zinc gluconate. Also by means of sensitized sheep erythrocytes in vitro, cobalt and, to a lesser extent, manganese gluconates were shown to increase the functional activity of C1q. Conclusion. 3d-metal gluconates (Mn, Co, Cu, Zn) demonstrate immunocorrecting properties: increase the content of immunoglobulin G and its complexes with C1q, significantly decreasing as a result of cyclophosphamide effect; cobalt and manganese gluconates have a stimulating effect on the functional activity of complement by its classical pathway, which indicates different mechanisms of immunocorrection action of studied metal gluconates and requires further studies.

Electronic, IR, and NMR spectroscopy methods were used to study the interaction in the β-glycyrrhizic acid (GA)–2,8-dimethyl-5-[2´-(6″-methylpyridin-3″-yl)ethyl]-2,3,4,5-tetra-hydro-1 H -pyrido[4,3- b ]indole ( Dim ) system in an alcoholic medium. The complete assignment of signals in the 1 H and 13 C NMR spectra of Dim and GA in CD 3 OD was made for the individual components and for thier mixtures at different ratios. These data suggest the formation of a host–guest complex in this system. It is hypothesized that associates of GA molecules interact with Dim through Δ 12,13 –carbonyl group conjugated bonds in the triterpene moiety of GA that interact with the aromatic systems of the indole and pyridine moieties of Dim , as well as via an acid-base mechanism involving mainly the carboxy groups of glucuronic acid residues in the carbohydrate part of GA and the nitrogen atom of the tetrahydropyridine ring of Dim .

Исследованы процессы взаимодействия йодид-ионов с полисахаридами методом ЯМР-спектроскопии, оценена нанодисперсность йодбиоорганических соединений методом лазерного наноструктурного анализа.

Исследованы процессы взаимодействия йодид-ионов с полисахаридами методом ЯМР-спектроскопии, оценена нанодисперсность йодбиоорганических соединений методом лазерного наноструктурного анализа.