Endocrine-disrupting chemicals (EDCs) may contribute to the rising incidence of metabolic dysfunction-associated steatotic liver disease (MASLD). We investigated the potential of 10 environmentally relevant EDCs to affect key events of hepatic steatosis in HepG2 human hepatoblastoma cells. Increased lipid droplet formation, a key marker of steatosis, was induced by PFOA, bisphenol F, DDE, butylparaben, and DEHP, within the non-cytotoxic concentration range of 1 nM-25 μM. Cadmium also induced this effect, but at concentrations impairing cell viability (>1 μM). At non-cytotoxic concentrations, these compounds, along with bisphenol A, dysregulated major genes controlling lipid homeostasis. Cadmium, PFOA, DDE, and DEHP significantly upregulated the DGAT1 gene involved in triglyceride synthesis, while butylparaben increased the expression of the FAT/CD36 gene responsible for fatty acid uptake. Bisphenol A downregulated the CPT1A gene involved in fatty acid oxidation. No significant effects on lipid droplet accumulation or lipid metabolism-related genes were observed for PFOS, bisphenol S, and dibutyl phthalate. Among the tested EDCs, lipid accumulation positively correlated with the expression of SREBF1, DGAT1, and CPT1A. These findings provide additional evidence that EDCs can affect MASLD and highlight the utility of in vitro methods in the screening of EDCs with hazardous steatogenic and metabolism-disrupting properties.
- MeSH
- benzhydrylové sloučeniny toxicita MeSH
- buňky Hep G2 MeSH
- diacylglycerol-O-acyltransferasa genetika metabolismus MeSH
- diethylhexylftalát toxicita MeSH
- endokrinní disruptory * toxicita MeSH
- fenoly toxicita MeSH
- fluorokarbony toxicita MeSH
- kapryláty toxicita MeSH
- lidé MeSH
- metabolismus lipidů účinky léků MeSH
- sloučeniny bisfenolu A MeSH
- viabilita buněk účinky léků MeSH
- ztučnělá játra * chemicky indukované metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
The increasing use of industrial chemicals has raised concerns regarding exposure to endocrine-disrupting chemicals (EDCs), which interfere with developmental, reproductive and metabolic processes. Of particular concern is their interaction with adipose tissue, a vital component of the endocrine system regulating metabolic and hormonal functions. The SGBS (Simpson Golabi Behmel Syndrome) cell line, a well-established human-relevant model for adipocyte research, closely mimics native adipocytes' properties. It responds to hormonal stimuli, undergoes adipogenesis and has been successfully used to study the impact of EDCs on adipose biology. In this study, we screened human exposure-relevant doses of various EDCs on the SGBS cell line to investigate their effects on viability, lipid accumulation and adipogenesis-related protein expression. Submicromolar doses were generally well tolerated; however, at higher doses, EDCs compromised cell viability, with cadmium chloride (CdCl2) showing the most pronounced effects. Intracellular lipid levels remained unaffected by EDCs, except for tributyltin (TBT), used as a positive control, which induced a significant increase. Analysis of adipogenesis-related protein expression revealed several effects, including downregulation of fatty acid-binding protein 4 (FABP4) by dibutyl phthalate, upregulation by CdCl2 and downregulation of perilipin 1 and FABP4 by perfluorooctanoic acid. Additionally, TBT induced dose-dependent upregulation of C/EBPα, perilipin 1 and FABP4 protein expression. These findings underscore the importance of employing appropriate models to study EDC-adipocyte interactions. Conclusions from this research could guide strategies to reduce the negative impacts of EDC exposure on adipose tissue.
- MeSH
- adipogeneze * účinky léků MeSH
- buněčné linie MeSH
- endokrinní disruptory * toxicita MeSH
- fluorokarbony toxicita MeSH
- kapryláty toxicita MeSH
- lidé MeSH
- metabolismus lipidů účinky léků MeSH
- proteiny vázající mastné kyseliny * metabolismus genetika MeSH
- trialkylcínové sloučeniny toxicita MeSH
- tuková tkáň účinky léků metabolismus MeSH
- tukové buňky účinky léků metabolismus MeSH
- viabilita buněk * účinky léků MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Metabolic transformation of cancer cells leads to the accumulation of lactate and significant acidification in the tumor microenvironment. Both lactate and acidosis have a well-documented impact on cancer progression and negative patient prognosis. Here, we report that cancer cells adapted to acidosis are significantly more sensitive to oxidative damage induced by hydrogen peroxide, high-dose ascorbate, and photodynamic therapy. Higher lactate concentrations abrogate the sensitization. Mechanistically, acidosis leads to a drop in antioxidant capacity caused by a compromised supply of nicotinamide adenine dinucleotide phosphate (NADPH) derived from glucose metabolism. However, lactate metabolism in the Krebs cycle restores NADPH supply and antioxidant capacity. CPI-613 (devimistat), an anticancer drug candidate, selectively eradicates the cells adapted to acidosis through inhibition of the Krebs cycle and induction of oxidative stress while completely abrogating the protective effect of lactate. Simultaneous cell treatment with tetracycline, an inhibitor of the mitochondrial proteosynthesis, further enhances the cytotoxic effect of CPI-613 under acidosis and in tumor spheroids. While there have been numerous attempts to treat cancer by neutralizing the pH of the tumor microenvironment, we alternatively suggest considering tumor acidosis as the Achilles' heel of cancer as it enables selective therapeutic induction of lethal oxidative stress.
- MeSH
- acidóza patofyziologie MeSH
- citrátový cyklus účinky léků MeSH
- energetický metabolismus MeSH
- fyziologická adaptace MeSH
- glukosa metabolismus MeSH
- glykolýza MeSH
- kapryláty farmakologie MeSH
- koncentrace vodíkových iontů MeSH
- kyselina mléčná metabolismus MeSH
- lidé MeSH
- mitochondrie účinky léků metabolismus patologie MeSH
- nádorové buňky kultivované MeSH
- nádorové mikroprostředí * MeSH
- nádory farmakoterapie metabolismus patologie MeSH
- oxidační stres MeSH
- protinádorové látky farmakologie MeSH
- sulfidy farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Perfluoralkylated substances (PFASs) are persistent and bioaccumulative environmental contaminants. They are included on the list of emergent compounds monitored in the frame of HBM4EU project. OBJECTIVES: To analyze PFASs levels in human milk samples collected in the period 2006 through 2017, to follow their time trends, to assess the PFASs exposure in breastfed infants, to calculate the daily intake of PFASs and to compare it with the tolerable daily/weekly) intakes and to quantify risk from exposure using the hazard quotient and hazard index approach. MATERIAL AND METHODS: A broad spectrum of PFASs were analyzed by means of UHPLC-MS/MS in primipara human milk samples collected in four consecutive time periods 2006, 2010/11, 2014, and 2017; N = 46, 183, 164 and 232, respectively. Mothers living in urban and suburban residences were recruited after their delivery at maternity hospitals, and milk samples were taken within 2 and 8 weeks after delivery. The questionnaire was focused on possible sources of exposure, dietary habits and lifestyle. RESULTS: Only perfluorooctane sulfonate (PFOS) and perfluorooctanoid acid PFOA (in 2017, also perfluorononanoic acid (PFNA)) were quantified in more than 90% of analyzed human milk samples. In all sampling periods, the levels of PFOA were higher than those of PFOS (p < 0.05). A significant downward temporal trend (p < 0.001) was observed for both PFOA and PFOS levels. The median concentrations in sampling years 2006, 2010/11, 2014, and 2017 were 0.075, 0.059, 0.035, and 0.023 ng/mL for PFOA and 0.045, 0.031, 0.029, and 0.020 ng/mL for PFOS, respectively. In 2017, PFNA was also quantified in 99% of samples with the median concentration of 0.007 ng/mL. The levels of PFASs correlated with maternal sea fish consumption. No maternal age-related relationship was observed. Using the tolerably daily intake (TDI) values for PFOS and PFOA set by the European Food Safety Authority (EFSA) in 2008, the calculated daily intakes from breastfeeding were clearly below these limits. Using the new, more conservative EFSA Provisional Tolerably Weekly Intake (PTWI) values set in 2018, we demonstrated a considerable exceedance of PTWI, with a hazard index above 1. CONCLUSION: Significant time-related decreasing trends in the PFOS and PFOA levels in human milk were observed. Nevertheless, the body burden of infants from breastfeeding might pose an enhanced health risk to infants when the current PTWI values are applied. These findings strongly support the present EU efforts to phase out PFOA, its salts and PFOA related compounds. Since PFOS exposure there has still been widely detected despite PFOS usage reduction measures, the major exposure routes should be further monitored and, if possible, eliminated.
- MeSH
- biologický monitoring MeSH
- fluorokarbony * analýza MeSH
- kapryláty analýza MeSH
- kojenec MeSH
- kyseliny alkansulfonové * analýza MeSH
- látky znečišťující životní prostředí * analýza MeSH
- lidé MeSH
- mateřské mléko chemie MeSH
- tandemová hmotnostní spektrometrie MeSH
- těhotenství MeSH
- zvířata MeSH
- Check Tag
- kojenec MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
Perfluorooctanoic acid (PFOA) is an emerging persistent organic pollutant which has been identified at significant levels in soils. Existed ecotoxicological studies have mainly employed earthworms to evaluate the toxicity of PFOA. However, little information do we know about the toxicity of PFOA regarding soil microorganisms. Accordingly, the adverse effects of PFOA on microbial activity in a wheat soil under four fertilization treatments were investigated in this study. The microcalorimetric results revealed that the toxicity of PFOA on soil microbial activity in four treatments followed a descending sequence: Control (no fertilization), NK (no P fertilizer, but N and K fertilizers were used), PK (no N fertilizer, but P and K fertilizers were used), and NPK (N, P and K fertilizers were used). The soil sample with higher available P content had higher resistant to PFOA. There were significant differences in urease activity and alkaline phosphatase activity among the four fertilization treated soils. Molecular modeling studies clearly demonstrated that the binding of PFOA with alkaline phosphatase was more stable than with urease through electrostatic interaction, van der Waals force, and hydrogen bonds. These results are expected to provide more comprehensive information in toxicity of PFOA in soil environment.
- MeSH
- fluorokarbony * MeSH
- kapryláty MeSH
- průmyslová hnojiva MeSH
- pšenice MeSH
- půda * MeSH
- půdní mikrobiologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- Candida MeSH
- fytoterapie * metody MeSH
- kandidóza vulvovaginální * patofyziologie terapie MeSH
- kandidóza * etiologie terapie MeSH
- kapryláty terapeutické užití MeSH
- komplementární terapie * MeSH
- léčivé rostliny MeSH
- lidé MeSH
- měsíček MeSH
- tea tree oil terapeutické užití MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
We have evaluated the therapeutic effect of a compound mixture of caprylic acid (200 mg/kg fish), organic iron (0.2% of diet) and mannan oligosaccharide (0.4% of diet) in gilthead sea bream, Sparus aurata Linnaeus, infected with Sparicotyle chrysophrii Beneden et Hesse, 1863 in controlled conditions. One hundred and ten reared and S. chrysophrii-free fish (197 g) located in a cement tank were infected by the parasite two weeks following the addition of 150 S. chrysophrii-infected fish (70 g). Growth parameters and gill parasitic load were measured in treated against control fish after a ten-week-period. Differences in final weight, feed conversion ratio, specific growth rate and feed efficiency were not statistically significant between the experimental groups, suggesting no evident effect with respect to fish growth during the study period. Although the prevalence of S. chrysophrii was not affected by the mixture at the end of the experiment, the number of adults and larvae was significantly lower. The mean intensity encompassing the number of adults and larvae was 8.1 in treated vs 17.7 in control fish. Individual comparisons of gill arches showed that the preferred parasitism site for S. chrysophrii it the outermost or fourth gill arch, consistently apparent in fish fed the modified diet and in control fish. In conclusion, the combined application of caprylic acid, organic iron and mannan oligosaccharide can significantly affect the evolution of infection with S. chrysophrii in gilthead sea bream, being capable of reducing adult and larval stages of the monogenean. However, no difference in growth improvement was observed after the trial period, potentially leaving space for further optimisation of the added dietary compounds.
- MeSH
- fixní kombinace léků MeSH
- infekce červy třídy Trematoda farmakoterapie veterinární MeSH
- kapryláty farmakologie MeSH
- mannany farmakologie MeSH
- mořan zlatý parazitologie MeSH
- nemoci ryb farmakoterapie MeSH
- oligosacharidy farmakologie MeSH
- potravní doplňky MeSH
- Trematoda účinky léků MeSH
- železo farmakologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The spatial and temporal distribution of per- and polyfluoroalkyl substances (PFASs) in the open Western Mediterranean Sea waters was investigated in this study for the first time. In addition to surface water samples, a deep water sample (1390 m depth) collected in the center of the western basin was analyzed. Perfluorohexanoic acid (PFHxA), perfluoroheptanoic acid (PFHpA), perfluorooctanoic acid (PFOA), perfluorohexanesulfonate (PFHxS) and perfluorooctanesulfonate (PFOS) were detected in all samples and were the dominant PFASs found. The sum of PFAS concentrations (ΣPFASs) ranged 246-515 pg/L for surface water samples. PFASs in surface water had a relatively homogeneous distribution with levels similar to those previously measured in the Atlantic near the Strait of Gibraltar, in water masses feeding the inflow to the Mediterranean Sea. Higher concentrations of PFHxA, PFHpA and PFHxS were, however, found in the present study. Inflowing Atlantic water and river/coastal discharges are likely the major sources of PFASs to the Western Mediterranean basin. Slightly lower (factor of 2) ΣPFASs was found in the deep water sample (141 pg/L). Such a relatively high contamination of deep water is likely to be linked to recurring deep water renewal fed by downwelling events in the Gulf of Lion and/or Ligurian Sea.
- MeSH
- chemické látky znečišťující vodu analýza MeSH
- fluorokarbony analýza MeSH
- kapronáty analýza MeSH
- kapryláty analýza MeSH
- kyseliny alkansulfonové analýza MeSH
- kyseliny sulfonové analýza MeSH
- mořská voda analýza MeSH
- řeky MeSH
- voda MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Středozemní moře MeSH
Altered gap junctional intercellular communication (GJIC) has been associated with chemical carcinogenesis, where both chemical tumor promoters and chemopreventive agents (CPAs) are known to conversely modulate GJIC. The aim of this study was to investigate whether attenuation of chemically inhibited GJIC represents a common outcome induced by different CPAs, which could be effectively evaluated using in vitro methods. Rat liver epithelial cells WB-F344 were pretreated with a CPA for either 30 min or 24 h, and then exposed to GJIC-inhibiting concentration of a selected tumor promoter or environmental toxicant [12-O-tetradecanoylphorbol-13-acetate (TPA), lindane, fluoranthene, 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (DDT), perfluorooctanoic acid (PFOA), or pentachlorophenol]. Out of nine CPAs tested, quercetin and silibinin elicited the most pronounced effects, preventing the dysregulation of GJIC by all the GJIC inhibitors, but DDT. Metformin and curcumin attenuated the effects of three GJIC inhibitors, whereas the other CPAs prevented the effects of two (diallyl sulfide, emodin) or one (indole-3-carbinol, thymoquinone) GJIC inhibitor. Significant attenuation of chemically induced inhibition of GJIC was observed in 27 (50%) out of 54 possible combinations of nine CPAs and six GJIC inhibitors. Our data demonstrate that in vitro evaluation of GJIC can be used as an effective screening tool for identification of chemicals with potential chemopreventive activity.
- MeSH
- antikarcinogenní látky farmakologie MeSH
- DDT toxicita MeSH
- epitelové buňky účinky léků MeSH
- fluoreny toxicita MeSH
- fluorokarbony toxicita MeSH
- hexachlorcyklohexan toxicita MeSH
- játra cytologie účinky léků MeSH
- kapryláty toxicita MeSH
- karcinogeny toxicita MeSH
- krysa rodu rattus MeSH
- kultivované buňky MeSH
- kurkumin farmakologie MeSH
- metformin farmakologie MeSH
- mezerový spoj účinky léků metabolismus MeSH
- mezibuněčná komunikace účinky léků MeSH
- potkani inbrední F344 MeSH
- tetradekanoylforbolacetát toxicita MeSH
- viabilita buněk účinky léků MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The effect of dietary caprylic acid (CA) on Salmonella Enteritidis, as well as the surface treatment of chicken skin contaminated with Salmonella Enteritidis was evaluated. To evaluate the dietary effect of CA on Salmonella Enteritidis, the individually housed broiler chickens (n=48) were divided into 4 groups (positive control, negative control, 2.5 g/kg of CA in the feed, and 5 g/kg of CA in the feed). The feed of all groups, except the negative control, was artificially contaminated with Salmonella Enteritidis ATCC 13076 (10(7) colony-forming units/100 g of feed). Both concentrations of dietary CA significantly decreased counts of Salmonella Enteritidis in the crop and cecum of experimental chickens (p<0.05). The effect of CA in the crop contents was more pronounced than in the cecum. Surface treatment of chilled chicken halves with CA at 1.25 and 2.5 mg/mL significantly decreased Salmonella Enteritidis contamination of chicken skin (p<0.05). The sensory evaluation of the skin and meat showed that treatment of the skin with 1.25 mg/mL of CA worsened odor and appearance of the chicken skin, while sensory traits of chicken meat were not significantly affected. Taste and overall acceptability was not influenced by CA in both meat and skin. Treatment of the skin with 2.5 mg/mL of CA resulted in more pronounced changes of the skin odor and appearance. In conclusion, dietary CA reduced carriage of Salmonella Enteritidis in chickens, whereas surface-treatment reduced or eliminated Salmonella Enteritidis contamination in the processed bird.
- MeSH
- cékum mikrobiologie MeSH
- dieta veterinární MeSH
- kapryláty terapeutické užití MeSH
- krmivo pro zvířata MeSH
- kur domácí MeSH
- maso mikrobiologie MeSH
- počet mikrobiálních kolonií MeSH
- Salmonella enteritidis účinky léků MeSH
- salmonelová infekce u zvířat prevence a kontrola MeSH
- vole ptačí mikrobiologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
