Study of acute and subacute action of iron-molybdenum nanocluster polyoxometalates

There were no significant deviations from the norm in the functional state of the liver, kidneys, and pancreas in the study of the acute toxicity of iron-molybdenum buckyballs intended for targeted drug delivery. No accumulation of nanoparticles or deviation from the norm in any investigated parameter was detected in the study of subacute toxicity. © 2013 Pleiades Publishing, Ltd

Physicochemical and biochemical properties of the Keplerate-type nanocluster polyoxomolybdates as promising components for biomedical use

The paper discusses the results of a research on physicochemical and biochemical properties of the Keplerate-type molybdenum-based nanocluster polyoxometalates (POMs), which show promise in the field of biomedicine as a means of targeted drug delivery, including the transport to immune privileged organs. POMs can be considered as components of releasing systems, including the long-acting ones with feedback (for controlling the drug active component release rate). POMs are promising drugs for the treatment of anemia. Also, the paper deals with the results of studies of POM effect on living systems at the molecular and cellular levels, at that of individual organs, and on the organism as a whole. The mechanism and kinetics of POM destruction and possibilities of stabilization, the oscillatory phenomena manifestation, the formation of POM conjugates with bioactive substances which can be released during the destruction of POM, with polymer components, and with indicator fluorescent dyes, as well as forecasts for further research, are considered. © 2021, ITMO University. All rights reserved.The paper was prepared in the framework of implementation of the State Assignment from the Ministry of Education and Science of the Russian Federation (Projects Nos. AAAA-A20-120061990010-7 (FEUZ-2020-0052) and AAAA-A18-118020590107-0), as well as of the Program for Increasing Competitiveness of UrFU (financially supported according to the Decree No. 211 of the Government of the Russian Federation, Contract No. 02.A03.21.0006). The research aimed at creating the long-time drug release systems with feedback was carried out within the framework of the project of the Russian Science Foundation No. 19-73-00177

ОСОБЕННОСТИ ОБМЕНА БИОПОЛИМЕРОВ СОЕДИНИТЕЛЬНОЙ ТКАНИ В ПЕЧЕНИ КРЫС С АЛЛОКСАНОВЫМ ДИАБЕТОМ

Aim. Study of the exchange of liver and blood plasma biopolymers of alloxan diabetic rats.Materials and Methods. Diabetes mellitus was modeled in rats by single subcutaneous injection of alloxan tetrahydrate (170 mg per100 gbody weight). Blood glucose, glycosylated hemoglobin were controlled and morphometric study of the pancreas was carried out for the verification of the model. A month later, concentration of glycosaminoglycans, free hydroxyproline and the level of hyaluronidase and collagenolytic activity in plasma were determined. The total concentration of collagen, glycosaminoglycans, and their fractions, the level of hyaluronidase and collagenolytic activity in rat liver homogenate were measured.Results. The level of all the parameters of interest in the liver and blood plasma increased on 30 day after alloxan injection, the accumulation of glycosaminoglycans in the liver occurred mainly due to unsulfonated fraction.Conclusion. The development of experimental diabetes in rats is accompanied by activation of both decay processes and synthesis of biopolymers studied. Accumulation of total collagen and glycosaminoglycans was observed in rats’ liver, which probably lead to the fibrosis changes in it.Цель исследования – изучить особенности обмена биополимеров матрикса печени и плазмы крови крыс при аллоксановом диабете. Материал и методы. Сахарный диабет у крыс моделировали однократным подкожным введением аллоксана тетрагидрата в дозе 170 мг/кг массы тела животного (для верификации модели определяли в крови содержание глюкозы, гликозилированного гемоглобина, проводили морфометрическое исследование поджелудочной железы). Через 1 мес в плазме крови определяли концентрацию гликозаминогликанов, свободного гидроксипролина, уровень гиалуронидазной и коллагенолитической активности. В гомогенате печени крыс определяли концентрацию суммарного коллагена, гликозаминогликанов, их фракций, уровень гиалуронидазной и коллагенолитической активности. Результаты. На 30-е сут после введения аллоксана в плазме крови и печени крыс наблюдалось возрастание уровня всех исследуемых показателей, причем накопление гликозаминогликанов в печени происходило преимущественно за счет несульфатированной фракции. Заключение. Развитие экспериментального диабета у животных сопровождается активацией как процессов распада, так и синтеза исследуемых биополимеров. В печени крыс отмечается накопление суммарного коллагена и гликозаминогликанов, что, вероятно, служит причиной фиброзных изменений в исследуемом органе

Studying of safety of molybden nanocluster polyoxometalates intended for address delivery of medicinal substances

The chemical structure of buckyballs on a basis of polyoxometalates defines possibility of their use in quality nanocarriers for carrying over of medical products to the damaged fabrics. Buckyballs on the basis of molybdenum stability research is carried out in liquids with various pH, and also studying of their toxicity and accumulation after introduction in an organism. It is revealed that buckyballs on the basis of molybdenum possess low accumulation and high toxicity in relation to hepatocytes that is shown increase in an index of alteration of the last, damage microcirculation liver channels.Химическая структура букиболов на основе полиоксометаллатов определяет возможность их использования в качестве наноконтейнеров для переноса лекарственных средств в поврежденные ткани. Проведено исследование устойчивости букиболов на основе молибдена в жидкостях с различными pH, а также изучение их токсичности и кумулятивности при введении в организм. Обнаружено, что букиболы на основе молибдена обладают низкой кумулятивностью и высокой токсичностью по отношению к гепатоцитам, что проявляется в увеличении индекса альтерации последних, повреждении микроциркуляторного русла печени

Type 1 Diabetes Impairs Cardiomyocyte Contractility in the Left and Right Ventricular Free Walls but Preserves It in the Interventricular Septum

Type 1 diabetes (T1D) leads to ischemic heart disease and diabetic cardiomyopathy. We tested the hypothesis that T1D differently affects the contractile function of the left and right ventricular free walls (LV, RV) and the interventricular septum (IS) using a rat model of alloxan-induced T1D. Single-myocyte mechanics and cytosolic Ca2+ concentration transients were studied on cardiomyocytes (CM) from LV, RV, and IS in the absence and presence of mechanical load. In addition, we analyzed the phosphorylation level of sarcomeric proteins and the characteristics of the actin-myosin interaction. T1D similarly affected the characteristics of actin-myosin interaction in all studied regions, decreasing the sliding velocity of native thin filaments over myosin in an in vitro motility assay and its Ca2+ sensitivity. A decrease in the thin-filament velocity was associated with increased expression of β-myosin heavy-chain isoform. However, changes in the mechanical function of single ventricular CM induced by T1D were different. T1D depressed the contractility of CM from LV and RV; it decreased the auxotonic tension amplitude and the slope of the active tension-length relationship. Nevertheless, the contractile function of CM from IS was principally preserved. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.Funding: This work was supported by the Russian Science Foundation № 18-74-10059. The work was performed using the equipment of the Shared Research Center of Scientific Equipment of Institute of Immunology and Physiology

ATOMIC FORSE MICROSCOPY FOR ERYTHROCYTE RESEARCH IN EXPERIMENTAL DIABETES MELLITUS

The morphology of erythrocytes in experimental diabetes mellitus by atomic force microscopy was evaluated. Significant changes on the surface of erythrocytes in the form of echinocyte formation were founded

Macrophages role in the pathogenesis of toxic hepatitis in rats

In rats with acute toxic hepatitis caused by CL4 injection the macrophages modulating activity at early stages of the disease development lessens the inflammatory reaction manifestation, intensifies the recovery processes in the liver which are demonstrated by an increase in the number of binuclear hepatocytes and mitosis cells.У крыс с острым токсическим гепатитом, вызванным введением CL4 модулирование активности макрофагов на ранних этапах развития заболевания уменьшает выраженность воспалительной реакции, усиливает восстановительные процессы в печени, проявляющиеся в увеличении количества двуядерных и делящихся митозом гепатоцитов. При этом значительно снижается показатели эндогенной интоксикации и интенсивность свободнорадикального окисления

The modulling influence of macrophages on recovery of structural changes of vascular tunic of eye in experimental diabetes

We showed that macrophages regulate a character and degree ot inflammatory process in pigmented layer and vascular tunic of eye in diabetic retinitis. Meanwhile, the modulation of their functional activity by the preparation «Tamerite» have resulted in regeneration of quantity and their functioning of melanocyte of pigment tunic and stimulation of angiogenesis vascular tunic of eye.В результате экспериментального исследования было установлено, что в условиях диабетической ретинопатии макрофаги определяют характер и выраженность воспалительного процесса пигментной и сосудистой оболочки глаза. Модуляция их функциональной активности препаратом «Тамерит» способствовала восстановлению популяции и функционирования меланоцитов пигментного слоя, стимуляции ангиогенеза в сосудистой оболочке глаза и обратному развитию склеротических изменений

Investigation of chronical toxicity of molybdenum and iron-molybdenum nanocluster polyoxometallates

It was conducted research of chronical toxicity of nanocluster polyoxometallates with type structure of buckyball (fullerene) intended for address delivery of medicines in an organism. Absence of accumulation of molybdenum in an organism of rats was established at daily intramuscular introduction of water solutions of both preparations within a month. On the basis of the analysis of biochemical tests and indicators of peripheral blood essential decrease in toxicity iron- molybdenum buckyballs in comparison with molybdenum ones was revealed (there was absence of an inflammation, cytolysis and infringements of a functional condition of bodies at chronic action iron- molybdenum polyoxometallates).Проведено исследование хронической токсичности нанокластерных полиоксометаллатов со структурой типа букибола (фуллерена), предназначенных в качестве средств адресной доставки лекарственных веществ в организме. Установлено отсутствие аккумулирования молибдена в организме крыс при ежедневном внутримышечном введении водных растворов обоих препаратов в течение месяца. На основании анализа биохимических тестов и показателей периферической крови выявлено существенное снижение токсичности железо-молибденовых букиболов по сравнению с молибденовыми (отсутствие воспаления, цитолиза и нарушения функционального состояния органов при хроническом действии железо-молибденовых полиоксометаллатов)