Q57223792
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Cyanobacterial harmful blooms (CyanoHABs) pose a global ecological problem, and their lipopolysaccharides (LPS) are among the bioactive compounds they release. Previous studies on CyanoHAB-LPS from single cyanobacterial species have shown varying bioactivities in different in vitro cell models. In this study, we isolated LPS from 19 CyanoHAB samples collected at 18 water bodies in the Czech Republic over two consecutive seasons. The proportions of cyanobacteria, Gram-negative bacteria (G-), and other bacteria in the biomass were determined by qPCR, while the cyanobacterial genera were identified using light microscopy. In vitro models of keratinocytes (HaCaT), the intestinal epithelium (co-culture of differentiated Caco-2 cells and peripheral blood mononuclear cells - PBMC), and PBMC alone were treated with isolated LPS at concentrations of 50, 100, and 1 μg/ml, respectively. The endotoxin activities of these concentrations were within the range measured in the aquatic environment. Approximately 85-90% of the samples displayed biological activity. However, the potency of individual LPS effects and response patterns varied across the different in vitro models. Furthermore, the observed activities did not exhibit a clear correlation with the taxonomic composition of the phytoplankton community, the relative share of microbial groups in the biomass, endotoxin activity of the LPS, or LPS migration and staining pattern in SDS-PAGE. These findings suggest that the effects of CyanoHAB-LPS depend on the specific composition and abundance of various LPS structures within the complex environmental sample and their interactions with cellular receptors.
- MeSH
- biomasa MeSH
- Caco-2 buňky MeSH
- leukocyty mononukleární MeSH
- lidé MeSH
- lipopolysacharidy * toxicita MeSH
- sinice * MeSH
- škodlivý vodní květ MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Freshwater cyanobacterial harmful blooms (CyanoHABs) produce a variety of toxic and bioactive compounds including lipopolysaccharides (LPSs). The gastrointestinal tract can be exposed to them via contaminated water even during recreational activities. However, there is no evidence of an effect of CyanoHAB LPSs on intestinal cells. We isolated LPSs of four CyanoHABs dominated by different cyanobacterial species and LPSs of four laboratory cultures representing the respective dominant cyanobacterial genera. Two intestinal and one macrophage cell lines were used to detect in vitro pro-inflammatory activity of the LPS. All LPSs isolated from CyanoHABs and laboratory cultures induced cytokines production in at least one in vitro model, except for LPSs from the Microcystis PCC7806 culture. LPSs isolated from cyanobacteria showed unique migration patterns in SDS-PAGE that were qualitatively distinct from those of endotoxins from Gram-negative bacteria. There was no clear relationship between the biological activity of the LPS and the share of genomic DNA of Gram-negative bacteria in the respective biomass. Thus, the total share of Gram-negative bacteria, or the presence of Escherichia coli-like LPSs, did not explain the observed pro-inflammatory activities. The pro-inflammatory properties of environmental mixtures of LPSs from CyanoHABs indicate their human health hazards, and further attention should be given to their assessment and monitoring.
Bile acids (BAs) are important steroidal molecules with a rapidly growing span of applications across a variety of fields such as supramolecular chemistry, pharmacy, and biomedicine. This work provides a systematic review on their transport processes within the enterohepatic circulation and related processes. The focus is laid on the description of specific or less-specific BA transport proteins and their localization. Initially, the reader is provided with essential information about BAs' properties, their systemic flow, metabolism, and functions. Later, the transport processes are described in detail and schematically illustrated, moving step by step from the liver via bile ducts to the gallbladder, small intestine, and colon; this description is accompanied by descriptions of major proteins known to be involved in BA transport. Spillage of BAs into systemic circulation and urine excretion are also discussed. Finally, the review also points out some of the less-studied areas of the enterohepatic circulation, which can be crucial for the development of BA-related drugs, prodrugs, and drug carrier systems.
BACKGROUND: LA-12 is a new platinum (IV) drug with promising cytotoxic effects in a wide range of cancer cell lines. Its confluence-dependent effects were compared with cisplatin (CDDP) and oxaliplatin (L-OHP) in HT-29 cells. MATERIALS AND METHODS: Cytotoxicity was determined by MTT test, eosin exclusion assay, and cell number quantification. The cell cycle was analysed using propidium iodide DNA staining (flow cytometry), apoptosis by phosphatidylserine externalisation (annexin-V assay), mitochondrial membrane potential by flow cytometry, nuclear morphology by means of fluorescence microscopy, and PARP cleavage by Western blotting. RESULTS: While L-OHP and CDDP were practically inactive in the subconfluent cell population, LA-12 showed a similar toxicity in both subconfluent and growing populations. All compounds induced apoptosis, although with different potentials. CONCLUSION: LA-12 was able to overcome confluence-dependent resistance of HT-29 cells observed for other platinum compounds, which may have potential therapeutic use in slowly growing tumours.
- MeSH
- adenokarcinom farmakoterapie MeSH
- amantadin analogy a deriváty farmakologie MeSH
- apoptóza účinky léků MeSH
- buněčná adheze účinky léků MeSH
- buňky HT-29 MeSH
- chemorezistence MeSH
- cisplatina farmakologie MeSH
- lidé MeSH
- nádory tračníku farmakoterapie patologie MeSH
- organoplatinové sloučeniny farmakologie MeSH
- protinádorové látky farmakologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Platinum-based complexes are important drugs for the treatment of cancer diseases. Compared to the commonly used Pt(II) compounds cisplatin and oxaliplatin, the recently reported complexes containing Pt(IV) seem to have several advantages; they are safer, can be used orally, have a higher scope of anticancer effect, and do not show cross-resistance to cisplatin. In the first part, cisplatin and oxaliplatin, and satraplatin and LA-12, the Pt(II) and Pt(IV) complexes, respectively, are characterised. Their structures, range of action and side effects are described. In the following part, the mechanisms of their effects are briefly explained, i.e., transport of the active agents to cells, adduct formation, biotransformation pathways, etc. The last part deals with protective mechanisms of the cell, differences in DNA repair mechanisms, and ideas concerning the development of resistance to these drugs.
- MeSH
- chemorezistence genetika imunologie účinky léků MeSH
- cisplatina aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- farmakokinetika MeSH
- fenitrotion terapeutické užití MeSH
- financování organizované MeSH
- glutathion škodlivé účinky terapeutické užití MeSH
- lidé MeSH
- nežádoucí účinky léčiv komplikace MeSH
- organokovové sloučeniny aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- organoplatinové sloučeniny aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- protinádorové látky aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- sloučeniny platiny aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- Check Tag
- lidé MeSH
Methylated chrysenes (MeChry) are important cigarette smoke constituents and 5-MeChry has been listed as possibly carcinogenic to humans. Although a major attention has been in past paid especially to mutagenic, tumor-initiating effects of MeChry, little is known about toxic effects of MeChry related to tumor promotion. As the position of methyl group has been repeatedly observed to determine genotoxic effects of MeChry, we examined both genotoxic and nongenotoxic effects of MeChry, using rat liver cell lines as experimental models. All six MeChry were relatively efficient aryl hydrocarbon receptor (AhR) agonists, with 3- and 6-MeChry being the most potent inducers of the AhR-mediated reporter gene activity. All six compounds disrupted contact inhibition in rat liver epithelial WB-F344 cells, a process previously reported to be AhR-dependent, suggesting that MeChry may interfere with cell cycle control in an AhR-dependent manner. In contrast, only 5- and 6-MeChry were found to acutely inhibit gap junctional intercellular communication (GJIC), another parameter correlating with tumor promoting effects of xenobiotics. Both 5- and 6-MeChry were efficient inducers of mRNA expression of enzymes involved in metabolic activation of polycyclic aromatic hydrocarbons, including cytochromes P450 1A1/1B1 and aldo-keto reductase 1C9. However, only 5-MeChry, and not 6-MeChry, induced significant formation of DNA adducts in rat liver epithelial cells, which corresponded with its ability to induce high accumulation of cells in S-phase. On the other hand, 5-MeChry induced neither apoptosis related to DNA damage nor phosphorylation of p53 tumor suppressor. Taken together, our results suggest that methyl group position may affect both genotoxic and nongenotoxic effects of MeChry, such as formation of DNA adducts and inhibition of GJIC. All MeChry showed a potency to disrupt cell proliferation control, while 5-MeChry was a single compound inducing DNA damage, disruption of cell cycle control and inhibition of GJIC in rat liver cells.
- MeSH
- adukty DNA metabolismus MeSH
- buněčný cyklus účinky léků MeSH
- chryseny toxicita MeSH
- enzymová indukce účinky léků MeSH
- epitelové buňky účinky léků MeSH
- financování organizované MeSH
- játra účinky léků MeSH
- karcinogeny toxicita MeSH
- krysa rodu rattus MeSH
- mezerový spoj MeSH
- mezibuněčná komunikace účinky léků MeSH
- receptory aromatických uhlovodíků fyziologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
