cyanotoxin
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In this study, a simple and low-cost method to synthesize iron(III) oxide nanopowders in large quantity was successfully developed for the photocatalytic degradation of microcystin-LR (MC-LR). Two visible light-active iron(III) oxide samples (MG-9 calcined at 200 °C for 5 h and MG-11 calcined at 180 °C for 16 h) with a particle size of 5-20 nm were prepared via thermal decomposition of ferrous oxalate dihydrate in air without any other modifications such as doping. The synthesized samples were characterized by X-ray powder diffraction, 57Fe Mössbauer spectroscopy, transmission electron microscopy, Brunauer-Emmett-Teller (BET) specific surface area analysis, and UV-visible diffuse reflectance spectroscopy. The samples exhibited similar phase composition (a mixture of α-Fe2O3 and γ-Fe2O3), particle size distribution (5-20 nm), particle morphology, and degree of agglomeration, but different specific surface areas (234 m2 g-1 for MG-9 and 207 m2 g-1 for MG-11). The results confirmed higher photocatalytic activity of the catalyst with higher specific surface area. The highest photocatalytic activity of the sample to decompose MC-LR was observed at solution pH of 3.0 and catalyst loading of 0.5 g L-1 due to large amount of MC-LR adsorption, but a little iron dissolution of 0.0065 wt% was observed. However, no iron leaching was observed at pH 5.8 even though the overall MC-LR removal was slightly lower than at pH 3.0. Thus, the pH 5.8 could be an appropriate operating condition for the catalyst to avoid problems of iron contamination by the catalyst. Moreover, magnetic behavior of γ-Fe2O3 gives a possibility for an easy separation of the catalyst particles after their use.
HL1-hT1 cell line represents adult human liver stem cells (LSCs) immortalized with human telomerase reverse transcriptase. In this study, HL1-hT1 cells were found to express mesenchymal markers (vimentin, CD73, CD90/THY-1 and CD105) and an early hepatic endoderm marker FOXA2, while not expressing hepatic progenitor (HNF4A, LGR5, α-fetoprotein) or differentiated hepatocyte markers (albumin, transthyretin, connexin 32). In response to microcystin-LR (MC-LR), a time- and concentration-dependent formation of MC-positive protein bands in HL1-hT1 cells was observed. Cellular accumulation of MC-LR occurred most likely via mechanisms independent on organic anion transporting polypeptides (OATPs) or multidrug resistance (MDR) proteins, as indicated (a) by a gene expression analysis of 11 human OATP genes and 4 major MDR genes (MDR1/P-glycoprotein, MRP1, MRP2 and BCRP); (b) by non-significant effects of OATP or MDR1 inhibitors on MC-LR uptake. Accumulation of MC-positive protein bands in HL1-hT1 cells was associated neither with alterations of cell viability and growth, dysregulations of ERK1/2 and p38 kinases, reactive oxygen species formation, induction of double-stranded DNA breaks nor modulations of stress-inducible genes (ATF3, HSP5). It suggests that LSCs might have a selective, MDR1-independent, survival advantage and higher tolerance towards MC-induced cytotoxic, genotoxic or cancer-related events than differentiated adult hepatocytes, fetal hepatocyte or malignant liver cell lines. HL1-hT1 cells provide a valuable in vitro tool for studying effects of toxicants and pharmaceuticals on LSCs, whose important role in the development of chronic toxicities and liver diseases is being increasingly recognized.
- MeSH
- apoptóza účinky léků fyziologie MeSH
- dospělé kmenové buňky účinky léků metabolismus MeSH
- hepatocyty účinky léků metabolismus MeSH
- inhibitory enzymů toxicita MeSH
- játra cytologie účinky léků metabolismus MeSH
- karcinogeny toxicita MeSH
- lidé MeSH
- mikrocystiny toxicita MeSH
- transformované buněčné linie MeSH
- viabilita buněk účinky léků fyziologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Microcystin-LR (MC-LR) is a potent hepatotoxin produced by harmful cyanobacterial blooms (CyanoHABs). MC-LR targets highly differentiated hepatocytes expressing organic anion transporting polypeptides OATP1B1 and OATP1B3 that are responsible for hepatocellular uptake of the toxin. The present study utilized an advanced 3D in vitro human liver model Hepoid-HepaRG based on the cultivation of collagen-matrix embedded multicellular spheroids composed of highly differentiated and polarized hepatocyte-like cells. 14-d-old Hepoid-HepaRG cultures showed increased expression of OATP1B1/1B3 and sensitivity to MC-LR cytotoxicity at concentrations >10 nM (48 h exposure, EC20 = 26 nM). MC-LR induced neither caspase 3/7 activity nor expression of the endoplasmic reticulum stress marker gene BiP/GRP78, but increased release of pro-inflammatory cytokine IL-8, indicating a necrotic type of cell death. Subcytotoxic (10 nM) and cytotoxic (≥100 nM) MC-LR concentrations disrupted hepatocyte functions, such as xenobiotic metabolism phase-I enzyme activities (cytochrome P450 1A/1B) and albumin secretion, along with reduced expression of CYP1A2 and ALB genes. MC-LR also decreased expression of HNF4A gene, a critical regulator of hepatocyte differentiation and function. Genes encoding hepatobiliary membrane transporters (OATP1B1, BSEP, NTCP), hepatocyte gap junctional gene connexin 32 and the epithelial cell marker E-cadherin were also downregulated. Simultaneous upregulation of connexin 43 gene, primarily expressed by liver progenitor and non-parenchymal cells, indicated a disruption of tissue homeostasis. This was associated with a shift in the expression ratio of E-cadherin to N-cadherin towards the mesenchymal cell marker, a process linked to epithelial-mesenchymal transition (EMT) and hepatocarcinogenesis. The effects observed in the human liver cell in vitro model revealed mechanisms that can potentially contribute to the MC-LR-induced promotion and progression of hepatocellular carcinoma (HCC). Hepoid-HepaRG cultures provide a robust, accessible and versatile in vitro model, capable of sensitively detecting hepatotoxic effects at toxicologically relevant concentrations, allowing for assessing hepatotoxicity mechanisms, human health hazards and impacts of environmental hepatotoxins, such as MC-LR.
- MeSH
- hepatocelulární karcinom * MeSH
- kadheriny MeSH
- lékové postižení jater * MeSH
- lidé MeSH
- mikrocystiny toxicita metabolismus MeSH
- mořské toxiny * MeSH
- nádory jater * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Cylindrospermopsin (CYN) is a cyanobacterial toxin that occurs in aquatic environments worldwide. It is known for its delayed effects in animals and humans such as inhibition of protein synthesis or genotoxicity. The molecular targets and the cell physiological mechanisms of CYN, however, are not well studied. As inhalation of CYN-containing aerosols has been identified as a relevant route of CYN uptake, we analyzed the effects of CYN on protein expression in cultures of immortalized human bronchial epithelial cells (16HBE14o-) using a proteomic approach. Proteins whose expression levels were affected by CYN belonged to several functional clusters, mainly regulation of protein stability, cellular adhesion and integration in the extracellular matrix, cell proliferation, cell cycle regulation, and completion of cytokinesis. With a few exceptions of upregulated proteins (e.g., ITI inhibitor of serine endopeptidases and mRNA stabilizer PABPC1), CYN mediated the downregulation of many proteins. Among these, centrosomal protein 55 (CEP55) and osteonectin (SPARC) were significantly reduced in their abundance. Results of the detailed semi-quantitative Western blot analyses of SPARC, claudin-6, and CEP55 supported the findings from the proteomic study that epithelial cell adhesion, attenuation of cell proliferation, delayed completion of mitosis, as well as induction of genomic instability are major effects of CYN in eukaryotic cells.
- MeSH
- epitelové buňky * účinky léků metabolismus MeSH
- lidé MeSH
- proteiny buněčného cyklu MeSH
- proteomika MeSH
- toxiny kmene Cyanobacteria * toxicita MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Cylindrospermopsin, a potent hepatotoxin produced by harmful cyanobacterial blooms, poses environmental and human health concerns. We used a 3D human liver in vitro model based on spheroids of HepG2 cells, in combination with molecular and biochemical assays, automated imaging, targeted LC-MS-based proteomics, and lipidomics, to explore cylindrospermopsin effects on lipid metabolism and the processes implicated in hepatic steatosis. Cylindrospermopsin (1 μM, 48 h) did not significantly affect cell viability but partially reduced albumin secretion. However, it increased neutral lipid accumulation in HepG2 spheroids while decreasing phospholipid levels. Simultaneously, cylindrospermopsin upregulated genes for lipogenesis regulation (SREBF1) and triacylglycerol synthesis (DGAT1/2) and downregulated genes for fatty acid synthesis (ACLY, ACCA, FASN, SCD1). Fatty acid uptake, oxidation, and lipid efflux genes were not significantly affected. Targeted proteomics revealed increased levels of perilipin 2 (adipophilin), a major hepatocyte lipid droplet-associated protein. Lipid profiling quantified 246 lipid species in the spheroids, with 28 significantly enriched and 15 downregulated by cylindrospermopsin. Upregulated species included neutral lipids, sphingolipids (e.g., ceramides and dihexosylceramides), and some glycerophospholipids (phosphatidylethanolamines, phosphatidylserines), while phosphatidylcholines and phosphatidylinositols were mostly reduced. It suggests that cylindrospermopsin exposures might contribute to developing and progressing towards hepatic steatosis or metabolic dysfunction-associated steatotic liver disease (MASLD).
- MeSH
- alkaloidy * farmakologie MeSH
- bakteriální toxiny * metabolismus MeSH
- buněčné sféroidy účinky léků metabolismus MeSH
- buňky Hep G2 MeSH
- homeostáza účinky léků MeSH
- játra * metabolismus účinky léků MeSH
- lidé MeSH
- lipidomika MeSH
- lipogeneze účinky léků MeSH
- metabolismus lipidů * účinky léků MeSH
- proteomika MeSH
- toxiny kmene Cyanobacteria * MeSH
- uracil * analogy a deriváty metabolismus MeSH
- viabilita buněk účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Sinice (cyanobakterie), dříve nazývané „modrozelené řasy", jsou primitivní životní formy. Jsou to jedny nejstarších organismů na Zemi a lze je nalézt stejně tak na pevnině, jako ve sladkých či slaných vodách. Voda bohatá na živiny, jako např. v eutrofizovaných jezerech, pomalu tekoucích vodních tocích nebo zemědělských a rekreačních nádržích, může rychle zarůst sínicemi. Jsou-li vhodné podmínky, původně čirá voda se během několika dnů zbarví zeleně, modrozeleně nebo rudohnědě. Vytvoří se tzv. „vodní kveť' produkující toxiny (cyanotoxiny), které mohou být nebezpečné všem živočichům, včetně člověka. Cyanotoxiny můžeme zhruba rozdělit na neurotoxicky účinné anatoxiny a hepatotoxicky účinné microcystiny, microviridin, nodularin a cylindrospermopsin. Toxiny sinic jsou nejčastější příčinou otrav po vypití závadné vody či konzumaci mořských živočichů. Některé cyanotoxiny by mohly být zneužity pro vojenské či teroristické účely, jsou na seznamu látek, které podléhají mezinárodním kontrolním režimům.
Cyanobacteria, formerly called "blue-green algae", are relatively simple, primitive life forms. Cyanobacteria represent one of the original organisms on the Earth and are found throughout the world in terrestrial, freshwater and marine habitats. Nutrient-rich bodies of water such as eutrophic lakes, slowly running watercourses. agricultural and holiday basins, may support a rapid growth of cyanobacteria. When conditions are good, a clear design of water can become very turbid with a green, blue-green or reddish-brown growth within just a few days. It is the freshwater habitat that typically experiences a cyanobacteria "bloom". Sometimes blooms may produce toxins (cyanotoxins) that are potentially dangerous to animals, including humans. Cyanotoxins can be divided into neurotoxic anatoxins and hepatotoxic microcystins, microviridin, nodularin and cylindrospermopsin. Algal toxins represent a major source of poisonings due to drinking water contamination and seafood consumption. Some cyanotoxins could be misused for military or terrorist purposes and there are in the list of compound who be liable to international control regime.
Cylindrospermopsin (CYN) has been recognized as a potent waterborne hepatotoxin with an increasing environmental occurrence. However, CYN effects on the specific populations of hepatic cells involved in liver tissue development, renewal, and regeneration, have not been characterized yet. We used human embryonic stem cells to analyze the hepatic differentiation stage-specific effect of CYN. Our results strongly suggest that CYN might contribute to the development of chronic adverse outcomes by disrupting liver tissue homeostasis in terms of (1) cellular stress and damage induced in the mature differentiated hepatocytes, which was associated with a necrotic cell death and thus possibly also inflammatory responses; (2) selective elimination of HNF4α+ cells from populations of progenitor cells and immature hepatocytes during hepatic differentiation, which could possibly lead to an impaired liver renewal and regeneration; (3) impaired hepatic functions of immature hepatocytes, such as decreased albumin secretion or increased lipid accumulation, which could contribute to the development of liver steatosis; and (4) survival of the immature and AFP-expressing cells with the limited ability to further differentiate, which could represent a tumor-promoting condition.
- MeSH
- albuminy metabolismus MeSH
- apoptóza MeSH
- bakteriální toxiny toxicita MeSH
- buněčná diferenciace účinky léků MeSH
- hepatocytární jaderný faktor 4 metabolismus MeSH
- hepatocyty účinky léků MeSH
- játra účinky léků MeSH
- kmenové buňky MeSH
- lidé MeSH
- lidské embryonální kmenové buňky MeSH
- metabolismus lipidů MeSH
- nekróza MeSH
- oxidační stres účinky léků MeSH
- sinice MeSH
- sladká voda MeSH
- uracil analogy a deriváty toxicita MeSH
- viabilita buněk účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Components of cyanobacterial water blooms were quantified in aerosols above agitated water surfaces of five freshwater bodies. The thoracic and respirable aerosol fraction (0.1-10 μm) was sampled using a high-volume sampler. Cyanotoxins microcystins were detected by LC-MS/MS at levels 0.3-13.5 ng/mL (water) and < 35-415 fg/m3 (aerosol). Lipopolysaccharides (endotoxins) were quantified by Pyrogene rFC assay at levels < 10-119 EU/mL (water) and 0.13-0.64 EU/m3 (aerosol). Cyanobacterial DNA was detected by qPCR at concentrations corresponding to 104-105 cells eq./mL (water) and 101-103 cells eq./m3 (aerosol). Lipopolysaccharides isolated from bloom samples induced IL-6 and IL-8 cytokine release in human bronchial epithelial cells Beas-2B, while extracted cyanobacterial metabolites induced both pro-inflammatory and cytotoxic effects. Bloom components detected in aerosols and their bioactivities observed in upper respiratory airway epithelial cells together indicate that aerosols formed during cyanobacterial water blooms could induce respiratory irritation and inflammatory injuries, and thus present an inhalation health risk.
- MeSH
- aerosoly MeSH
- chromatografie kapalinová MeSH
- lidé MeSH
- lipopolysacharidy analýza MeSH
- mikrocystiny toxicita MeSH
- sinice * metabolismus MeSH
- sladká voda analýza MeSH
- tandemová hmotnostní spektrometrie MeSH
- toxiny kmene Cyanobacteria * MeSH
- voda MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Wild birds are continually exposed to many anthropogenic and natural stressors in their habitats. Over the last decades, mass mortalities of wild birds constitute a serious problem and may possibly have more causations such as natural toxins including cyanotoxins, parasitic diseases, industrial chemicals and other anthropogenic contaminants. This study brings new knowledge on the effects of controlled exposure to multiple stressors in birds. The aim was to test the hypothesis that influence of cyanobacterial biomass, lead and antigenic load may combine to enhance the effects on birds, including modulation of antioxidative and detoxification responses. Eight treatment groups of model species Japanese quail (Coturnix coturnix japonica) were exposed to various combinations of these stressors. The parameters of detoxification and oxidative stress were studied in liver and heart after 30 days of exposure. The antioxidative enzymatic defense in birds seems to be activated quite efficiently, which was documented by the elevated levels and activities of antioxidative and detoxification compounds and by the low incidence of damage to lipid membranes. The greatest modulations of glutathione level and activities of glutathione-S-transferase, glutathione peroxidase, glutathione reductase, superoxide dismutase, catalase and lipid peroxidation were shown mostly in the groups with combined multiple exposures. The results indicate that the antioxidative system plays an important role in the protective response of the tissues to applied stressors and that its greater induction helps to protect the birds from more serious damage. Most significant changes of these "defense" parameters in case of multiple stressors suggest activation of this universal mechanism in situation with complex exposure and its crucial role in protection of the bird health in the environment.
- MeSH
- bakteriální toxiny farmakologie MeSH
- biologické markery analýza MeSH
- Coturnix metabolismus virologie MeSH
- glutathion metabolismus MeSH
- glutathionperoxidasa metabolismus MeSH
- glutathionreduktasa metabolismus MeSH
- glutathiontransferasa metabolismus MeSH
- játra účinky léků metabolismus MeSH
- katalasa metabolismus MeSH
- látky reagující s kyselinou thiobarbiturovou metabolismus MeSH
- mikrocystiny farmakologie MeSH
- mořské toxiny farmakologie MeSH
- newcastleská nemoc patofyziologie MeSH
- olovo farmakologie MeSH
- oxidační stres MeSH
- peroxidace lipidů MeSH
- sinice chemie patogenita MeSH
- srdce účinky léků MeSH
- superoxiddismutasa metabolismus MeSH
- virus newcastleské nemoci patogenita MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
