Mitochondrial Electron Transport Chain in Heavy Metal-Induced Neurotoxicity: Effects of Cadmium, Mercury, and Copper

To clarify the role of mitochondrial electron transport chain (mtETC) in heavy-metal-induced neurotoxicity, we studied action of Cd2+, Hg2+, and Cu2+ on cell viability, intracellular reactive oxygen species formation, respiratory function, and mitochondrial membrane potential of rat cell line PC12. As found, the metals produced, although in a different way, dose- and time-dependent changes of all these parameters. Importantly, Cd2+ beginning from 10 [mu]M and already at short incubation time (3 h) significantly inhibited the FCCP-uncoupled cell respiration; besides, practically the complete inhibition of the respiration was reached after 3 h incubation with 50 [mu]M Hg2+ or 500 [mu]M Cd2+, whereas even after 48 h exposure with 500 [mu]M Cu2+, only a 50% inhibition of the respiration occurred. Against the Cd2+-induced cell injury, not only different antioxidants and mitochondrial permeability transition pore inhibitors were protective but also such mtETC effectors as FCCP and stigmatellin (complex III inhibitor). However, all mtETC effectors used did not protect against the Hg2+- or Cu2+-induced cell damage. Notably, stigmatellin was shown to be one of the strongest protectors against the Cd2+-induced cell damage, producing a 15–20% increase in the cell viability. The mechanisms of the mtETC involvement in the heavy-metal-induced mitochondrial membrane permeabilization and cell death are discussed

Доклінічні дослідження стреспротективної активності гомеопатичних гранул «Tонус-актив»

Aim. To perform the preclinical studies of the stress-protective activity of a new “Tonus-Aktiv” homeopathic medicinal product.Materials and methods. The stress-protective effect of the “Tonus-Aktiv” homeopathic medicinal product (MP) and the reference drug – “Stress-gran” homeopathic granules were studied on the model of neuromuscular tension by Selye. The stress-protective effect of the drugs was assessed by the conventional methods described in the scientific literature and the corresponding current instructional guidelines. All factual material was processed by variational statistics methods using parametric (Newman-Keuls test) and non-parametric methods of analysis (Kruskal-Wallis, Mann-Whitney).Results and discussion. It was found that “Tonus-Aktiv” had a pronounced gastro-protective effect, reducing the area of ulcers by almost 3 times, having a statistically significant antioxidant effect, reducing the level of TBA (thiobarbituric acid) active products in the liver homogenate. It did not have a normalizing effect on the protein metabolism, but it did contribute to enhancing energy-supplying metabolic processes: aerobic glycolysis indicated by a reliable increase of the pyruvic acid level in the blood serum, and lipolysis, as evidenced by a significantly higher level of the total blood lipids. “Tonus-Aktiv” showed a pronounced antioxidant activity: it reduced the TBA level of active products in the liver homogenate. At the same time, the level of endogenous antioxidant of reduced glutathione was observed to be lower than in the stressed animals against the background of the “Tonus-Aktiv” application. It indicates the physiological nature of the stress protective activity of the drug.Conclusions. A moderate stress-protective activity of “Tonus-Aktiv” homeopathic granules can be observed; it is caused by antioxidant properties, as well as a probable activating effect on the hypothalamic-pituitary-adrenal system, which may be manifested by the protective action.Цель работы. Проведение доклинических исследований по изучению стресспротективной активности нового гомеопатического лекарственного средства «Тонус-актив».Материалы и методы. Стресспротективное действие гомеопатического лекарственного средства (ЛС) «Тонус-актив» и средства сравнения гомеопатических гранул «Стресс-гран» изучали на модели нервно-мышечного напряжения по Селье. Оценка стресспротективного действия ЛС проводилась общепринятыми методами, описанными в научной литературе и соответствующих действующих методических рекомендациях. Весь фактический материал обрабатывали методами вариационной статистики с использованием параметрических (Нʼюмана-Кейлса) и непараметрических методов анализа (Крускала-Уоллиса, Манна-Уитни).Результаты и их обсуждение. Установлено, что «Тонус-актив» проявлял выраженное гастропротективное влияние, снижая площадь язв почти в 3 раза, оказывал статистически вероятное антиоксидантное действие, снижая уровень ТБК (тиобарбитуровокислых) активных продуктов в гомогенате печени. Он не осуществлял нормализирующего действия на белковый обмен, однако способствовал усилению энергоснабжающих метаболических процессов: аэробного гликолиза, на что указывает достоверное повышение уровня пировиноградной кислоты в сыворотке крови, и липолиза, о чем свидетельствует достоверно более высокий уровень общих липидов в сыворотке крови. «Тонус-актив» проявлял выраженную антиоксидантную активность – снижал уровень ТБК активных продуктов в гомогенате печени. Вместе с этим на фоне применения «Тонус-актив» наблюдали более низкий относительно стрессированных животных уровень эндогенного антиоксиданта восстановленного глютатиона, что свидетельствует о физиологическом характере стресспротективной активности ЛС.Выводы. Можно констатировать умеренную стресспротективную активность гомеопатических гранул «Тонус-актив», которая обусловлена антиоксидантными свойствами, а также вероятным активирующим влиянием на гипоталамо-гипофизарно-надпочечниковую систему, что может проявляться протективным действием.Мета роботи. Проведення доклінічних досліджень з вивчення стреспротективної активності нового гомеопатичного лікарського засобу «Тонус-актив».Матеріали та методи. Стреспротективну дію гомеопатичного лікарського засобу (ЛЗ) «Тонус-актив» та засобу порівняння гомеопатичних гранул «Стрес-гран» вивчали на моделі нервово-м’язового напруження за Сельє. Оцінка стреспротективної дії ЛЗ проводилася загальноприйнятими методами, описаними у науковій літературі, та відповідними чинними методичними рекомендаціми. Весь фактичний матеріал обробляли методами варіаційної статистики з використанням параметричних (Ньюмана-Кейлса) та непараметричних методів аналізу (Крускала-Уолліса, Манна-Уїтні).Результати та їх обговорення. Встановлено, що «Тонус-актив» виявляв виражений гастропротективний вплив, знижуючи площу виразок майже в 3 рази, чинив статистично вірогідну антиоксидантну дію, знижуючи рівень ТБК (тіобарбітуровокислих) активних продуктів у гомогенаті печінки. Він не чинив нормалізуючої дії на білковий обмін, проте сприяв посиленню енергозабезпечуючих метаболічних процесів, зокрема аеробного гліколізу, на що вказує вірогідне підвищення рівня кислоти піровиноградної у сироватці крові, та ліполізу, про що свідчить вірогідно вищий рівень загальних ліпідів у сироватці крові. «Тонус-актив» виявляв виражену антиоксидантну активність – знижував рівень ТБК активних продуктів у гомогенаті печінки. Разом із цим на фоні застосування «Тонус-активу» спостерігали нижчий щодо стресованих тварин рівень ендогенного антиоксиданту відновленого глютатіону, що засвідчує фізіологічний характер стреспротективної активності ЛЗ.Висновки. Можна констатувати помірну стреспротективну активність гомеопатичних гранул «Тонус-актив», яка обумовлена антиоксидантними властивостями, а також імовірним активізуючим впливом на гіпоталамо-гіпофізарно-наднирникову систему, що може виявлятись протективною дією

Structure and properties of lymphocytes’ surfaces in patients with chronic lymphoblastic leucosis

In the investigation that was performed, the authors studied the structure and properties of lymphocytes’ surfaces in patients with chronic lymphoblastic leukemia with application of atomic force microscopy technology. It was stated that development of chronic lymphoblastic leukemia is characterized with circulation of immature forms of lymphocytic series in peripheral bloodstream, for which increase of surface potential by 456% (p<0.05) as compared with control group, is typica

Polymorphism of gene glutathion-s-transferase pi in teenagers from Buryat ethnic group living in the Irkutsk region

Background. Human glutathione-S-transferases play an important role in phase II detoxification process. But polymorphism in the GSTP1 gene has not been studied in certain populations. Aim: to determine the distribution of allele and genotype frequencies of GSTP1 gene in teenagers from Buryat ethnic group. Materials and methods. Blood samples were obtained from 55 teenagersfrom Buryat ethnic group. There were 28 males and 27 females with an age of 14.05 ± 0.99 years over the range of 13 to 16. DNA was isolated from blood samples. The polymerase chain reaction was used to amplify A313G and C341T markers of the GSTP1 gene. Chi-square testing was used to evaluate the significant difference of the GSTP1 genotype frequencies between observed and expected values. Results. Allele and genotype frequencies of A313G and C341T markers GSTP1 were determined in teenagers from Buryat ethnic group. The study showed that the frequencies of A and G alleles at the A313G marker were 0.809 and 0.191 while those of C and T alleles at the C341T marker were 0.973 and 0.027, respectively. The distribution of the genotype frequencies at the A313G marker were consistent with expected in a Hardy - Weinberg equilibrium (χ2 = 0.77; d.f. = 1; p > 0.05). However, the distribution of the genotype frequencies at the C341T marker were not consistent with expected in a Hardy - Weinberg equilibrium (χ2 = 0.043; d.f. = 1; p < 0.05). It was because the homozygous of T allele was not found in the ethnic group of Buryat

GLUTATION-S-TRANSPHERASE GENES POLYMORPHISM IN THE DIFFERENT ETHNIC GROUPS OF CHILDREN

The results of genotyping of blood samples of russian and buryat children on I/D polymorphism of GSTM1, GSTT1 genes by polymerase chain reaction are given. Absence of ethnic particularities in frequency deletion genotypes of GSTM1, GSTT1 genes is shown in this article

Organization of medical care for children in Ukraine (review of literature)

The realization of high quality medical measures for protecting children’s health remains an important issue at the stage of reforming the domestic medicine. The aim of this work was to study and analyze the system of medical aid for children in Ukraine. The research focused on normative-legal acts regulating the organization of medical aid for children. The research methods are informative, retrospective, historical, logical and analytical. The analysis of normative-legal documents regulating the organization of rendering of medical aid for children established their formality and economic groundlessness. According to January 2017, only 35 documents were included into the Registry of medical technological documents in the direction of «Pediatrics». It means that many children’s pathological states are not covered by standardization, what reduces the quality of medical aid. The national programs for the improvement of health status of children remained unrealized due to the lack of funding, ill-coordinated links between program implementers, the lack of effective monitoring of the quality and results of realizing the state programs. The implementation result of IMChI strategy was the reduction of mortality rate in children of different age groups in the pilot regions. In terms of reforming the combined model (model III) is the most effective and acceptable for pediatric care rendering. The population expenses reach nearly half of the total funding of the sector, what demonstrates the inconsistencies between the real state of children’s assurance in the health care system of Ukraine and national normative acts. It was determined the necessity of structural reorganization of the system, the optimization of beds number, the increase of medical care funding from state and local budgets, the raising of resource efficiency of health care system and the continued development and implementation of modern protocols (standards) for the treatment of children pathologies

Glutathione S-transferase polymorphism in ethnic groups living in Eastern Siberia

The role of glutathione S-transferase for the life of the cell and the entire organism is related to their participation in the processes of detoxification of xenobiotics and antioxidant protection. Genetic variability of glutathione S-transferases appears in the form of different enzymatic activity of the corresponding protein products. In this study, a comparative analysis was conducted on the frequency of genotypes of three genes in the glutathione S-transferases gene superfamily (GSTM1, GSTT1, GSTP1) from representatives of two ethnic groups, Russian and Buryat. To this end, genetic typing of DNA samples was performed by polymerase chain reaction. Statistically significant differences in the frequency of occurrence of alleles A, B, C of the GSTP1 gene (р = 0.026) were found between the groups of teenagers compared. It was found that the frequency of the allele A, which codes for the active variant enzyme, is significantly higher in the Buryat ethnic group (p = 0.012). The allele B, the product of which is a “slow” version of the enzyme, was significantly more common in the Russian ethnic group (p = 0.014). In the GSTM1 and GSTT1 genes, no statistically significant differences in the frequency of occurrence of “zero” and “functional” genotypes between the compared groups of teenagers were found. However, there was a tendency to increase in the frequency of the “zero” genotype of the GSTM1 gene in the Russian ethnic group. In addition, the frequency of the “zero” genotype in two genes GSTM1 and GSTT1 at once was almost two times higher in the Russian ethnic group than in the Buryat ethnic group