Latest Publications

@article{simek_lc-msms_2019,

title = {LC-MS/MS study of in vivo fate of hyaluronan polymeric micelles carrying doxorubicin.},

author = {Matěj Šimek and Martina Hermannová and Daniela Šmejkalová and Tereza Foglová and Karel Souček and Lucia Binó and Vladimír Velebný},

doi = {10.1016/j.carbpol.2018.12.104},

issn = {1879-1344 0144-8617},

year  = {2019},

date = {2019-04-01},

journal = {Carbohydrate polymers},

volume = {209},

pages = {181–189},

abstract = {A better understanding of in vivo behavior of nanocarriers is necessary for further improvement in their development. Here we present a novel approach, where both the matrix and the drug can be analyzed by LCMS/MS after one sample handling. The developed method was applied for the comparison of pharmacokinetic profile of free and encapsulated doxorubicin (DOX) in oleyl hyaluronan (HA-C18:1) polymeric micelles. The results indicated that nanocarriers were rapidly dissociated upon in vivo administration. Despite this fact, the administration of encapsulated DOX led to its longer circulation time and enhanced tumor targeting. This effect was not observed injecting blank HA-C18:1 micelles followed by unencapsulated DOX. Biodistribution studies and molecular weight estimation of the carrier matrix indicated relatively high stability of HA-C18:1 ester bond in bloodstream and complete elimination of the derivative within 72 h. The proposed methodology provides a novel strategy to elucidate the pharmacokinetic behavior of polysaccharide-based drug delivery systems.},

note = {Place: England},

keywords = {*Micelles, Animals, Biodistribution, Chromatography, Doxorubicin, Doxorubicin/*chemistry/pharmacokinetics, Drug Carriers/*chemistry, Drug Liberation, Female, Hyaluronan, Hyaluronic Acid/*chemistry, Liquid, Mice, Molecular Weight, Pharmacokinetics, Polymeric micelles, Tandem Mass Spectrometry, Tissue Distribution},

pubstate = {published},

tppubtype = {article}

}

@article{hofmanova_dietary_2017,

title = {Dietary fatty acids specifically modulate phospholipid pattern in colon cells with distinct differentiation capacities.},

author = {Jiřina Hofmanová and Josef Slavík and Petra Ovesná and Zuzana Tylichová and Jan Vondráček and Nicol Straková and Alena Hyršlová Vaculová and Miroslav Ciganek and Alois Kozubík and Lucie Knopfová and Jan Šmarda and Miroslav Machala},

doi = {10.1007/s00394-016-1196-y},

issn = {1436-6215 1436-6207},

year  = {2017},

date = {2017-06-01},

journal = {European journal of nutrition},

volume = {56},

number = {4},

pages = {1493–1508},

abstract = {PURPOSE: Although beneficial effects of the dietary n-3 docosahexaenoic acid (DHA) or butyrate in colon carcinogenesis have been implicated, the mechanisms of their action are not fully clear. Here, we investigated modulations of composition of individual phospholipid (PL) classes, with a particular emphasis on cardiolipins (CLs), in colon cells treated with DHA, sodium butyrate (NaBt), or their combination (DHA/NaBt), and we evaluated possible associations between lipid changes and cell fate after fatty acid treatment. METHODS: In two distinct human colon cell models, foetal colon (FHC) and adenocarcinoma (HCT-116) cells, we compared patterns and composition of individual PL classes following the fatty acid treatment by HPLC-MS/MS. In parallel, we measured the parameters reflecting cell proliferation, differentiation and death. RESULTS: In FHC cells, NaBt induced primarily differentiation, while co-treatment with DHA shifted their response towards cell death. In contrast, NaBt induced apoptosis in HCT-116 cells, which was not further affected by DHA. DHA was incorporated in all main PL types, increasing their unsaturation, while NaBt did not additionally modulate these effects in either cell model. Nevertheless, we identified an unusually wide range of CL species to be highly increased by NaBt and particularly by DHA/NaBt, and these effects were more pronounced in HCT-116 cells. DHA and DHA/NaBt enhanced levels of high molecular weight and more unsaturated CL species, containing DHA, which was specific for either differentiation or apoptotic responses. CONCLUSIONS: We identified a wide range of CL species in the colon cells which composition was significantly modified after DHA and NaBt treatment. These specific CL modulations might contribute to distinct cellular differentiation or apoptotic responses.},

note = {Place: Germany},

keywords = {Apoptosis, Apoptosis/drug effects, Butyrate, Butyric Acid/pharmacology, Cardiolipins, Caspase 3/genetics/metabolism, Cell Differentiation/*drug effects, Cell Line, Cell Proliferation/drug effects, Colon cancer, Colon/cytology/*drug effects, Docosahexaenoic acid, Docosahexaenoic Acids/*pharmacology, HCT116 Cells, Humans, Phospholipids, Phospholipids/*chemistry, Tandem Mass Spectrometry, Tumor},

pubstate = {published},

tppubtype = {article}

}

@article{smerdova_inflammatory_2013,

title = {Inflammatory mediators accelerate metabolism of benzo[a]pyrene in rat alveolar type II cells: the role of enhanced cytochrome P450 1B1 expression.},

author = {Lenka Smerdová and Jiří Neča and Jana Svobodová and Jan Topinka and Jana Schmuczerová and Alois Kozubík and Miroslav Machala and Jan Vondráček},

doi = {10.1016/j.tox.2013.09.001},

issn = {1879-3185 0300-483X},

year  = {2013},

date = {2013-12-01},

journal = {Toxicology},

volume = {314},

number = {1},

pages = {30–38},

abstract = {Long-term deregulated inflammation represents one of the key factors contributing to lung cancer etiology. Previously, we have observed that tumor necrosis factor-α (TNF-α), a major pro-inflammatory cytokine, enhances genotoxicity of benzo[a]pyrene (B[a]P), a highly carcinogenic polycyclic aromatic hydrocarbon, in rat lung epithelial RLE-6TN cells, a model of alveolar type II cells. Therefore, we analyzed B[a]P metabolism in RLE-6TN cells under inflammatory conditions, simulated using either recombinant TNF-α, or a mixture of inflammatory mediators derived from activated alveolar macrophage cell line. Inflammatory conditions significantly accelerated BaP metabolism, as evidenced by decreased levels of both parent B[a]P and its metabolites. TNF-α altered production of the metabolites associated with dihydrodiol-epoxide and radical cation pathways of B[a]P metabolism, especially B[a]P-dihydrodiols, and B[a]P-diones. We then evaluated the role of cytochrome P450 1B1 (CYP1B1), which is strongly up-regulated in cells treated with B[a]P under inflammatory conditions, in the observed effects. The siRNA-mediated CYP1B1 knock-down increased levels of B[a]P and reduced formation of stable DNA adducts, thus confirming the essential role of CYP1B1 in B[a]P metabolism under inflammatory conditions. TNF-α also reduced expression of aldo-keto reductase 1C14, which may compete with CYP1B1 for B[a]P-7,8-dihydrodiol and divert it from the formation of ultimate B[a]P dihydrodiol epoxide. Together, the present data suggests that the CYP1B1-catalyzed metabolism of polycyclic aromatic hydrocarbons might contribute to their enhanced bioactivation and genotoxic effects under inflammatory conditions.},

note = {Place: Ireland},

keywords = {Animals, Aryl Hydrocarbon Hydroxylases/*biosynthesis/genetics, ATP Binding Cassette Transporter, Benzo(a)pyrene/*metabolism, Blotting, Cell Line, Conditioned, Culture Media, CYP1B1, Cytochrome P-450 CYP1B1, Cytokines/metabolism, DNA adducts, Inflammation, Inflammation Mediators/*pharmacology, metabolism, Oxidoreductases Acting on Aldehyde or Oxo Group Donors/biosynthesis/genetics, Polycyclic aromatic hydrocarbons, Pulmonary Alveoli/cytology/drug effects/*metabolism, Rats, Real-Time Polymerase Chain Reaction, RNA, Small Interfering, Subfamily B/biosynthesis/genetics, Tandem Mass Spectrometry, Transfection, Western},

pubstate = {published},

tppubtype = {article}

}