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The role of intestine and liver in glucuronidation of the imidazo- and triazoloacridinone antitumor agents, C-1311 and C-1305: High affinity substrates for UGT1A10
PublikacjaCelem przeprowadzonych badań było określenie roli poszczególnych izoform UDP-glukuronylotransferazy (UGT)oraz mikrosomów jelita(HIM)i wątroby (HLM) wyizolowanych od różnych pacjentów w metabolizmie pochodnych akrydonu, związków C-1311 i C-1305. Wykazano, że rodziną UGT katalizującą przemiany C-1305 i C-1311 jest UGT1A, z najwyższą aktywnością wykazywaną przez pozawątrobowy izoenzym UGT1A10. Rozkład aktywności frakcji mikrosomalnych...
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Influence of selenium and/or magnesium on alleviation alcohol induced oxidative stress in rats, normalization function of liver and changes in serum lipid parameters
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Intestinal, liver and lipid disorders in genetically obese rats are more efficiently reduced by dietary milk thistle seeds than their oil
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Interspecific distribution and co-associations of chemical elements in the liver tissue of marine mammals from the Polish Economical Exclusive Zone, Baltic Sea
PublikacjaPrzeprowadzono analizy próbek wątroby ssaków morskich z Polskiej Strefy Ekonomicznej Morza Bałtyckiego w celu oznaczenia szerokiej gamy pierwiastków (mikro- i makroelementy) z wykorzystaniem takich technik analitycznych jak ICP-MS, ICP-AES oraz CV-AAS.Badano zależności pomiędzy zawartością poszczególnych pierwiastków a wiekiem, płcią, miejscem bytowania, sposobem odżywiania i gatunkiem ssaków.
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Modulation of carcinogen metabolizing cytochromes p450 in rat liver and kidney by cabbage and sauerkraut juices: comparison with the effects of indole-3-carbinol and phenethyl isothiocyanate
PublikacjaThis study investigated the effect of raw cabbage and sauerkraut juices on the activity and expression of CYP1A1, 1A2, 1B1 and 2B in Wistar rat liver and kidney. The results were compared with those of two commercially available products of glucosinolates degradation: indole-3-carbinol (I3C) and phenethyl isothiocyanate (PEITC). Significant differences in the effect of the cabbage juices as well as I3C and PEITC between the liver...
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Detoxification of the tricyclic antidepressant opipramol and its analog – IS-noh by UGT enzymes before and after activation by phase I enzymes in rat liver microsomes
PublikacjaThe present studies were carried out to evaluate the simultaneous one-pot metabolism of opipramol (IS-opi) and analog (IS-noh) by phase I and phase II enzymes present in rat liver microsomes (RLM) as an alternative to separate testing with recombinant enzymes. This approach allows for more time-saving and cost-effective screening of the metabolism of newly discovered drugs. We also considered that the lack of results for phase...
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Flavin monooxygenases, FMO1 and FMO3, not cytochrome p450 isoenzymes, contribute to metabolism of anti-tumour triazoloacridinone, C-1305, in liver microsomes and HepG2 cells.
PublikacjaCelem pracy było określenie roli wybranych enzymów frakcji mikrosomalnej komórek wątroby w metabolizmie pochodnej triazoloakrydonu, związku C-1305. Wykazano, że badana pochodna ulega transformacji wobec frakcji enzymów izolowanych z hepatocytów szczurzych i ludzkich oraz jest metabolizowana przez komórki linii HepG2. Badania wykazały ponadto, że enzymami odpowiedzialnymi za obserwowane przemiany były monooksygenazy flawinowe, FMO1...
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Diet supplemented either with dried chicory root or chicory inulin significantly influence kidney and liver mineral content and antioxidative capacity in growing pigs
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Dietary chicory root and chicory inulin trigger changes in energetic metabolism, stress prevention and cytoskeletal proteins in the liver of growing pigs – a proteomic study
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High-dose testosterone enanthate supplementation boosts oxidative stress, but exerts little effect on the antioxidant barrier in sedentary adolescent male rat liver
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Protective impact of extract from Aronia melanocarpa berries against low-level exposure to cadmium-induced liver damage: a study in a rat model
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Growth Performance, Chemical Composition of Fillets, Liver and Intestinal Histology, and Expression of Lipid-Dependent Genes in Common Carp (Cyprinus carpio) Fed Artificial Diets
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MRI assessment of ectopic fat accumulation in pancreas, liver and skeletal muscle in patients with obesity, overweight and normal BMI in correlation with the presence of central obesity and metabolic syndrome
PublikacjaPurpose: Obesity, defined as a body mass index (BMI) exceeding 30 kg/m2, is a serious health problem, which can be called an epidemic on a global scale and is one of the most important causes of preventable death. The aim of this study was to assess ectopic fat accumulation in pancreas, liver and skeletal muscle in patients with obesity, overweight and normal BMI in correlation with metabolic syndrome (MetS). Patients and methods:...
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N-doped carbon nanospheres as selective fluorescent probes for mercury detection in contaminated aqueous media: chemistry, fluorescence probing, cell line patterning, and liver tissue interaction
PublikacjaA precise nano-scale biosensor was developed here to detect Hg2+ in aqueous media. Nitrogen-doped carbon nanospheres (NCS) created from the pyrolysis of melamine–formaldehyde resin were characterized by FESEM, XRD, Raman spectra, EDS, PL, UV–vis spectra, and N2 adsorption–desorption, and were used as a highly selective and sensitive probe for detecting Hg2+ in aqueous media. The sensitivity of NCS to Hg2+ was evaluated by photoluminescence...
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<p>Mechano-signalling, induced by fullerene C<sub>60</sub> nanofilms, arrests the cell cycle in the G2/M phase and decreases proliferation of liver cancer cells</p>
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In vitro enzyme kinetics and NMR-based product elucidation for glutathione S-conjugation of the anticancer unsymmetrical bisacridine C-2028 in liver microsomes and cytosol: major role of glutathione S-transferase M1-1 isoenzyme
PublikacjaThis work is the next step in studying the interplay between C-2028 (anticancer-active unsymmetrical bisacridine developed in our group) and the glutathione S-transferase/glutathione (GST/GSH) system. Here, we analyzed the concentration- and pH-dependent GSH conjugation of C-2028 in rat liver microsomes and cytosol. We also applied three recombinant human GST isoenzymes, which altered expression was found in various tumors. The...
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Manganese(II) tri-tert-butoxysilanethiolate complexes with imidazole based coligands. A neutral complex with four independent ligands and MNOS2 core (M=Mn) related to the liver alcohol dehydrogenase catalytic center (M=Zn)
PublikacjaReakcja silanotiolanu manganu(II) z imidazolem oraz dwiema jego metylowymi pochodnymi prowadzi do uzyskania kompleksów heteroleptycznych o różnym typie. Gdy do syntez wykorzystano 2-metyloimidazol uzyskano związek zawierający w komórce elementarnej dwie różniące się od siebie cząsteczki, powiązane wiązaniami wodorowymi typu N-H…S. W jednej z tych molekuł centralny atom manganu jest skoordynowany z czterema ligandami: dwoma podstawnikami...
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Effects of Three-Month Administration of High-Saturated Fat Diet and High-Polyunsaturated Fat Diets with Different Linoleic Acid (LA, C18:2n–6) to α-Linolenic Acid (ALA, C18:3n–3) Ratio on the Mouse Liver Proteome
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Stellate cells in livers of dogs with portal vein hypoperfusion
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Lipogranulomas and pigment granulomas in livers of dogs with portosystemic shunt
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Reduced colonic microbial diversity is associated with colitis in NHE3-deficient mice
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Terrestrial animal livers as a source of PCDD/Fs, PCBs and PBDEs in the diet
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A contribution to the moss and liverwort flora of the Reberce Nature Reserve at the Przemyśl Foothills (Western Carpathians, Poland)
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Liverpool One jako przykład przekształceń centrum miasta w oparciu o duży projekt urbanistyczny
PublikacjaArtykuł podsumowuje wynik analizy studium przypadku projektu Liverpool One, przekształcenia zdegradowanego centrum Liverpoolu w oparciu o prywatny projekt o mieszanym przeznaczeniu i duże centrum handlowe. Artykuł wskazuje na takie elementy jak proces realizacji, mechanizmy partnerstwa publiczno-prywatnego. Artykuł wskazuje także na aspekty projektu jak zjawiska prywatyzacji i utowarowienia przestrzeni miasta.
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Bioactive and bioavailability of minerals in rats loaded with cholesterol and kiwi fruit
PublikacjaThe aim of this study was to compare the content of polyphenols (TP), minerals, ascorbic acid (AA) and total antioxidant capacities (TAC) of conventional and organic kiwifruit ‘Hayward’ treated with ethylene after harvest and to determine their influence on plasma TAC, mineral content in the liver and bioavailability (RBV — relative bioavailability value) in rats fed diet containing cholesterol. Organic and conventionally grown...
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Methylmercury and total mercury content in soft tissues of two bird species wintering in the Baltic Sea near Gdansk, Poland
PublikacjaOf the various forms of Hg occurring in nature, (mono) methylmercury (MeHg) is an especially toxic form and practically all forms of Hg can be converted into MeHg as a result of natural processes. Total mercury (THg) and MeHg were determined in tissues of two piscivorous birds: razorbill Alca torda and black-throated loon Gavia arctica to provide baseline data on current mercury concentrations for liver, kidneys and pectoral muscle...
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Chemical composition of lipids isolated from selected organs and tissues of the raccoon dog (Nyctereutes procyonoides)
PublikacjaOur paper presents a qualitative analysis of particular lipid classes (phospholipids, triacylglycerols, cholesterol, free fatty acids) isolated from the tissues of raccoon dogs harvested in northeastern Poland. In all examined tissues (except for the liver) the dominant group of lipids were triacylglycerols. The amounts of lipids representing the other classes depended on the kind of tissue from which the fat was isolated. The...
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The correlation between the MRI-evaluated ectopic fat accumulation and the incidence of diabetes mellitus and hypertension depends on body mass index and waist circumference ratio.
PublikacjaThe widespread presence of overweight and obesity increases with every decade, and the number of people with body mass index (BMI) >30 kg/m2 has doubled in the last 30 years. The aim of the study is to assess the correlation between MRI-evaluated ectopic fat accumulation in pancreas, skeletal muscles and liver and the incidence of type 2 diabetes and hypertension, depending on BMI and waist circumference ratio. This prospective...
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Analysis of multi-class pharmaceuticals in fish tissues by ultra-high-performance liquid chromatography tandem mass spectrometry
PublikacjaA new sensitive method based on pressurized liquid extraction (PLE) and purification by gel permeation chromatography (GPC) prior to ultra-high-performance liquid chromatography coupled to tandem mass spectrometry (UHPLC–MS/MS) was developed for the determination in fish homogenate, liver and muscle of twenty pharmaceuticals compounds and metabolites from seven commonly used therapeutic families. An extensive matrix effect evaluation...
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Relationships between concentrations of selected organohalogen contaminants and thyroid hormones and vitamins A, E and D in Faroese pilot whales
PublikacjaPilot whales (Globicephala melas) from the Faroe Islands, North-East Atlantic, have high body concentrations of organohalogenated compounds (OHCs), such as polychlorinated biphenyls (PCBs), organochlorinated pesticides (OCPs) and brominated flame retardants (BFRs). The aim of the present study was to examine if and to what extent blood plasma and liver concentrations of several groups of these OHCs are related to concentrations...
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Splice variants of mitofusin 2 shape the endoplasmic reticulum and tether it to mitochondria
PublikacjaIn eukaryotic cells, different organelles interact at membrane contact sites stabilized by tethers. Mitochondrial mitofusin 2 (MFN2) acts as a membrane tether that interacts with an unknown partner on the endoplasmic reticulum (ER). In this work, we identified the MFN2 splice variant ERMIT2 as the ER tethering partner of MFN2. Splicing of MFN2 produced ERMIT2 and ERMIN2, two ER-specific variants. ERMIN2 regulated ER morphology,...
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Concentrations of heavy metals and PCBs in the tissues of European beavers (Castor fiber) captured in northeastern Poland
PublikacjaEuropean beavers (Castor fiber) from two regions were examined to identify exposure to persistent environmental contaminants. A reference group was comprised of six animals from the Forest Division of Srokowo, and an exposed group was comprised of five animals from the vicinity of a former military airport operated in 1918–1986—both from Warmia land in Poland. 137 Cs in beavers' muscles was considered negligible for the overall...
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Mercury concentration and the absolute and relative sizes of the internal organs in cormorants Phalacrocorax carbo (L. 1758) from the breeding colony by the Vistula Lagoon (Poland)
PublikacjaThis work analyses the effect of mercury on the condition of cormorants (Phalacrocorax carbo) from an extensive breeding colony in northern Poland, the largest in Europe. A total of 55 birds (44 adults and 11 immature) were obtained. Total mercury (Hg) concentrations were measured in the liver, kidneys, breast muscles, heart, gullet (oesophagus), stomach, intestines, trachea, lungs and eyeballs. The total body mass (TBM) and empty...
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Novel insights into conjugation of antitumor-active unsymmetrical bisacridine C-2028 with glutathione: characteristics of non-enzymatic and glutathione S-transferase-mediated reactions
PublikacjaUnsymmetrical bisacridines (UAs) are a novel potent class of antitumor-active therapeutics. A significant route of phase II drug metabolism is conjugation with glutathione (GSH), which can be non-enzymatic and/or catalyzed by GSH-dependent enzymes. The aim of this work was to investigate the GSH-mediated metabolic pathway of a representative UA, C 2028. GSH supplemented incubations of C-2028 with rat, but not with human, liver...
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Role of Human UDP-Glucuronosyltransferases in the Biotransformation of the Triazoloacridinone and Imidazoacridinone Antitumor Agents C-1305 and C-1311 : Highly Selective Substrates for UGT1A10
Publikacja5-Diethylaminoethylamino-8-hydroxyimidazoacridinone, C-1311 (NSC-645809), is an antitumor agent shown to be effective against breast cancer in phase II clinical trials. A similar compound, 5-dimethylaminopropylamino-8-hydroxytriazoloacridinone, C-1305, shows high activity against experimental tumors and is expected to have even more beneficial pharmacological properties than C-1311. Previously published studies showed that these...
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Characterization of fatty acid composition in Eurasian badger (Meles meles)
PublikacjaPolyunsaturated fatty acids (PUFAs, LA and ALA) are not synthesized in mammals in the absence of their essential fatty acid precursors. However, hibernating animals and animals sleeping through the winter need sufficiently high amounts of these acids. The Eurasian badger does not hibernate, but sleeps over winter. In the autumn the body weight of adult badgers increases even twofold, since they put on fat before the winter. Fat...
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Exploring avian exposure to parent polycyclic aromatic hydrocarbons (PAHs): Using the common eider Somateria mollissima in a global context
PublikacjaCompared to other organic contaminants, birds are rarely studied for their exposure to polycyclic aromatic hydrocarbons (PAHs), mainly due to their effective metabolization of parent PAHs. However, as some studies suggest, exposure to PAHs may result in adverse health effects including decreased survival, especially following oil spills. In the present study, we analyzed samples from a sea duck, the common eider Somateria mollissima...
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Distinction of clenbuterol intake from drug or contaminated food of animal origin in a controlled administration trial – the potential of enantiomeric separation for doping control analysis
PublikacjaThe differentiation of clenbuterol abuse and unintentional ingestion by contaminated meat is crucial with respect to the valuation of an adverse analytical finding in human sports doping control. The proportion of the two enantiomers of clenbuterol may serve as potential discriminating parameter. For the determination of the individual enantiomers, specific methods were developed and validated for the different matrices under investigation...
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Nanodiamonds Doped with Manganese for Applications in Magnetic Resonance Imaging
PublikacjaNanodiamonds (NDs) are emerging with great potential in biomedical applications like biomarking through fluorescence and magnetic resonance imaging (MRI), targeted drug delivery, and cancer therapy. The magnetic and optical properties of NDs could be tuned by selective doping. Therefore, we report multifunctional manganese-incorporated NDs (Mn-NDs) fabricated by Mn ion implantation. The fluorescent properties of Mn-NDs were tuned...
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Electrochemical simulation of enzymatic transformations studied for the selected antitumor acridine derivatives
PublikacjaThe elucidation of the metabolic pathways and the biotransformation mechanisms of potential drugs is a crucial point in drug development. It allows to know the activation routes of the new biologically active compounds, especially in respect to their possible toxicity. Generally, in vivo or in vitro experiments with liver microsomes or hepatocytes are performed. However, these testing schemes are tedious, time consuming and of...
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Electrochemistry meets enzymes: Investigation of the biotransformation pathway of C-1311 based on electrochemical simulation in comparison to in vitro methods.
PublikacjaThe knowledge of the metabolic pathways and the biotransformation of new drugs is one of the major challenges in pharmaceutical research. It is crucial for elucidation of degradation routes of the new biologically active compounds, especially in the area of possible toxicity. Conventional in vitro drug metabolism studies are based on incubating drug candidate with e.g. hepatocytes or, most importantly, liver cell microsomes and...
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Therapeutic Potential of Multifunctional Tacrine Analogues
PublikacjaTacrine is a potent inhibitor of cholinesterases (acetylcholinesterase and butyrylcholinesterase) that shows limiting clinical application by liver toxicity. In spite of this, analogues of tacrine are considered as a model inhibitor of cholinesterases in the therapy of Alzheimer’s disease. The interest in these compounds is mainly related to a high variety of their structure and biological properties. In the present review, we...
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T1 RELAXATION TIME CALLIBRATION IN MAGNETIC RESONANCE IMAGING USING NANODIAMOND PHANTOMS
PublikacjaMRI is increasingly used in radiation treatment planning because of the excellent soft tissue contrast in the obtained images. It allows more precise definition of the boundaries between healthy tissues and those affected by cancerous lesions. To obtain good image quality, the difference in signal between two types of tissue must be significant despite the noise so it must be properly calibrated. This calibration includes...
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Drug-drug interaction potential of antitumor acridine agent C-1748: The substrate of UDP-glucuronosyltransferases 2B7, 2B17 and the inhibitor of 1A9 and 2B7
PublikacjaBackground The compound 9-(2′-hydroxyethylamino)-4-methyl-1-nitroacridine (C-1748), the promising antitumor agent developed in our laboratory was determined to undergo phase I metabolic pathways. The present studies aimed to know its biotransformation with phase II enzymes – UDP-glucuronosyltransferases (UGTs) and its potential to be engaged in drug-drug interactions arising from the modulation of UGT activity. Methods UGT-mediated...
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Genome-wide DNA methylation profiling of the regenerative MRL/MpJ mouse and two normal strains
PublikacjaAims We aimed to identify the pivotal differences in the DNA methylation profiles between the regeneration capable MRL/MpJ mouse and reference mouse strains. Materials and Methods Global DNA methylation profiling was performed in ear pinnae, bone marrow, spleen, liver, heart from uninjured adult females of the MRL/MpJ and C57BL/6J and BALB/c. Results and conclusion A number of differentially methylated regions distinguishing between...
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Abuse or contamination? Ratio determination of clenbuterol enantiomers to distinguish between doping use and meat contamination
PublikacjaClenbuterol has been detected in urine of several athletes during routine doping control in the past years. Athletes claimed that the clenbuterol was ingested by eating contaminated meat. Providing analytical prove for this claim is difficult. clenbuterol consists of two enantiomers, R(-) and S(+)-clenbuterol. Currently available human and veterinary preparations were found to consist of a racemic mixture of both enantiomers. When...
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The II phase metabolism of endogenous and exogenous compounds, including antitumor chemotherapeutics
PublikacjaThe II phase metabolism, it is a set of metabolism and excretion pathways of endogenous as well as exogenous compounds including xenobiotics. UDP-glucuronyltransferases (UGTs; EC 2.4.1.17) are the most crucial representatives of II phase enzymes, which are responsible for the transformation of bilirubine and bile acids, steroids and thyroid hormones and lipids. Exogenous compounds, including drugs, carcinogens, environmental pollutants...
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Health-Promoting Effects of Ethylene-Treated Kiwifruit ‘Hayward’ from Conventional and Organic Crops in Rats Fed an Atherogenic Diet
PublikacjaKiwifruit is a subtropical fruit that is very popular among consumers. Kiwifruit ‘Hayward’ (Actinidia deliciosa C.F. Liang et A.R. Ferguson) is an important source of bioactive compounds and possesses high antioxidant capacity, but its value can be changed during ripening. The aim of this study was to compare the levels of total polyphenols (TP), ascorbic acid (AA), and total antioxidant capacities (TACs) of ethylene-treated and...
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Mercury concentrations in marine biota with special focus on grey and ringed seals
PublikacjaMarine organisms are exposed and sensitive to effects of environmental contamination by heavy metals including different forms of mercury. Baltic seals as the top predators of the marine ecosystem are even more endangered due to (considerable) longevity as well as a long biological half-time of toxin elimination. The concentrations of mercury in seals from the Baltic is poorly known, thus the aim of this work is to determine and...
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Synthesis, molecular structure, and metabolic stability of new series of N' -(2-alkylthio-4-chloro-5-methylbenzenesulfonyl)-1-(5-phenyl-1 H -pyrazol-1-yl)amidine as potential anti-cancer agents
PublikacjaA series of new N'-(2-alkylthio-4-chloro-5-methylbenzenesulfonyl)-1-(5-phenyl-1H-pyrazol-1-yl)amidine derivatives have been synthesized and evaluated in vitro by MTT assays for their antiproliferative activity against cell lines of colon cancer HCT-116, cervical cancer HeLa and breast cancer MCF-7. The studied compounds display selective activity mainly against HCT-116 and HeLa cells. Thus, five compounds show selective cytotoxic...