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

Humans are widely exposed to phthalates and their novel substitutes, and considering the negative health effects associated with some phthalates, it is crucial to understand population levels and exposure determinants. This study is focused on 300 urine samples from teenagers (aged 12-17) and 300 from young adults (aged 18-37) living in Czechia collected in 2019 and 2020 to assess 17 plasticizer metabolites as biomarkers of exposure. We identified widespread phthalate exposure in the study population. The diethyl phthalate metabolite monoethyl phthalate (MEP) and three di (2-ethylhexyl) phthalate metabolites were detected in the urine of >99% of study participants. The highest median concentrations were found for metabolites of low-molecular-weight (LMW) phthalates: mono-n-butyl phthalate (MnBP), monoisobutyl phthalate (MiBP) and MEP (60.7; 52.6 and 17.6 μg/L in young adults). 1,2-cyclohexanedicarboxylic acid diisononyl ester (DINCH) metabolites were present in 68.2% of the samples with a median of 1.24 μg/L for both cohorts. Concentrations of MnBP and MiBP were similar to other European populations, but 5-6 times higher than in populations in North America. We also observed large variability in phthalate exposures within the study population, with 2-3 orders of magnitude differences in urinary metabolites between high and low exposed individuals. The concentrations varied with season, gender, age, and lifestyle factors. A relationship was found between high levels of MEP and high overall use of personal care products (PCPs). Cluster analysis suggested that phthalate exposures depend on season and multiple lifestyle factors, like time spent indoors and use of PCPs, which combine to lead to the observed widespread presence of phthalate metabolites in both study populations. Participants who spent more time indoors, particularly noticeably during colder months, had higher levels of high-molecular weight phthalate metabolites, whereas participants with higher PCP use, particularly women, tended to have higher concentration of LMW phthalate metabolites.

• MeSH
• diethylhexylftalát * moč   MeSH
• kosmetické přípravky * analýza   MeSH
• kyseliny ftalové * moč   MeSH
• látky znečišťující životní prostředí * moč   MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• vystavení vlivu životního prostředí analýza   MeSH
• životní styl MeSH
• Check Tag
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Phthalates are chemicals interfering with the function of testosterone and are suspected to play a role in the emergence of neurodevelopmental diseases. This could be due to interference with brain development for which optimal testosterone levels are essential. We investigated the effect of prenatal and early postnatal exposure to a phthalate mixture on the anogenital distance (AGD), plasma testosterone levels and social behavior in rats. Pregnant rats were exposed to a mixture of diethylhexyl, diisononyl and dibutyl phthalate, each at a dose of 4.5 mg/kg/day, from gestational day 15 to postnatal day 4. A social interaction test was performed to assess sociability in the three ontogenetic stages (weaning, puberty, adulthood). AGD was measured in adulthood to assess changes in prenatal testosterone levels. Plasma testosterone levels were measured in adults by a radioimmunoassay. The total frequency and time of socio-cohesive interactions were decreased in phthalate exposed females in weaning, puberty and adulthood. Phthalate exposed males showed a decrease in the frequency of social interactions in weaning only. Shorter anogenital distance was observed in adult males exposed to phthalates. Decreased testosterone levels were observed in the exposed group in both sexes. Our results suggest that early developmental phthalate exposure may play an important role in the hormonal and behavioral changes associated with several neurodevelopmental diseases.

• MeSH
• dibutylftalát toxicita   MeSH
• diethylhexylftalát toxicita   MeSH
• krysa rodu rattus MeSH
• kyseliny ftalové toxicita   MeSH
• matka - expozice noxám škodlivé účinky   MeSH
• novorozená zvířata MeSH
• pohlavní dospělost MeSH
• pohlavní orgány účinky léků   patologie   MeSH
• potkani Wistar MeSH
• sociální chování * MeSH
• těhotenství MeSH
• testosteron krev   MeSH
• změkčovadla toxicita   MeSH
• zpožděný efekt prenatální expozice chemicky indukované   patologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Glucagon-like peptide-1 receptor (GLP1R) agonist is an incretin hormone and regulates glucose metabolism. However, phthalates, known as endocrine disruptors, can interfere with hormone homeostasis. In the present study, we aimed to estimate the impact of GLP1R agonist on di(2 ethylhexyl) phthalate (DEHP)-induced atherosclerosis. For this purpose, the effects of GLP1R agonist on various atherogenesis-related cellular processes and pathways were assessed in vascular smooth muscle cells (VSMCs). DEHP-induced cell proliferation and migration were significantly decreased by GLP1R agonist in VSMCs. Protein levels of matrix metalloproteinase (MMP)-2 and MMP-9 were significantly decreased in cells exposed to GLP1R agonist, compared with DEHP-treated cells. Expression levels of intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 were also reduced in GLP1R agonist-treated cells. Similarly, DEHP-associated phosphorylation of protein kinase B and extracellular signal-regulated kinase 1/2 was decreased in GLP1R agonist-treated cells, compared with DEHP-treated cells. Our findings suggest that treatment with GLP1R agonist counteracts the activation of pathways related to atherosclerosis.

• MeSH
• ateroskleróza chemicky indukované   farmakoterapie   metabolismus   patologie   MeSH
• diethylhexylftalát toxicita   MeSH
• inkretiny farmakologie   MeSH
• krysa rodu rattus MeSH
• kultivované buňky MeSH
• mezibuněčná adhezivní molekula-1 genetika   metabolismus   MeSH
• mitogenem aktivovaná proteinkinasa 3 genetika   metabolismus   MeSH
• proliferace buněk MeSH
• receptor pro glukagonu podobný peptid 1 agonisté   MeSH
• signální transdukce účinky léků   MeSH
• svaly hladké cévní účinky léků   metabolismus   patologie   MeSH
• změkčovadla toxicita   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Di-(2-ethylhexyl)-phthalate (DEHP) is a compound widely used as a plasticizer, which can leach from plastics into the environment and thus influence human health. The aim of this study was to analyze whether exposure to an environmentally relevant dose of DEHP during mice fetal development or puberty can cause long-lasting changes detectable month/s after the last exposure. We used a DEHP concentration relevant to a daily human intake of 2.4-3 μg/kg of body weight/day. CD1 outbred mice were treated either in utero or postnatally during puberty and analyzed in adulthood. Analyzing fertility parameters using morphometric, histologic, genomic and proteomic methods we showed that DEHP exposure leads to decreased sperm concentration and quality, in both experimental groups. Moreover, the changes in anogenital distance, seminal vesicle weight, and testicular gene expression suggest a disturbance of androgen signaling in exposed animals. In conclusion, we hereby present, that the prenatal and pubertal exposure to a low dose of DEHP negatively influenced reproductive endpoints in male mice, and some of the effects were persistent until adulthood.

• MeSH
• anální kanál anatomie a histologie   účinky léků   MeSH
• diethylhexylftalát toxicita   MeSH
• endokrinní disruptory toxicita   MeSH
• maternofetální výměna látek MeSH
• mužské pohlavní orgány anatomie a histologie   účinky léků   MeSH
• myši inbrední ICR MeSH
• pohlavní dospělost účinky léků   MeSH
• spermie účinky léků   MeSH
• těhotenství MeSH
• testis anatomie a histologie   účinky léků   MeSH
• vývojová regulace genové exprese účinky léků   MeSH
• změkčovadla toxicita   MeSH
• zpožděný efekt prenatální expozice chemicky indukované   genetika   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

To improve physical characteristics of plastics such as flexibility and durability, producers enrich materials with phthalates such as di-2-(ethylhexyl) phthalate (DEHP). DEHP is a high production volume chemical associated with metabolic and immune disruption in animals and humans. To reveal mechanisms implicated in phthalate-related disruption in the gastrointestinal system, male and female zebrafish were fed DEHP (3 ppm) daily for two months. At the transcriptome level, DEHP significantly upregulated gene networks in the intestine associated with helper T cells' (Th1, Th2, and Th17) specific pathways. The activation of gene networks associated with adaptive immunity was linked to the suppression of networks for tight junction, gap junctional intercellular communication, and transmembrane transporters, all of which are precursors for impaired gut integrity and performance. On a class level, DEHP exposure increased Bacteroidia and Gammaproteobacteria and decreased Verrucomicrobiae in both the male and female gastrointestinal system. Further, in males there was a relative increase in Fusobacteriia and Betaproteobacteria and a relative decrease in Saccharibacteria. Predictive algorithms revealed that the functional shift in the microbiome community, and the metabolites they produce, act to modulate intestinal adaptive immunity. This finding suggests that the gut microbiota may contribute to the adverse effects of DEHP on the host by altering metabolites sensed by both intestinal and immune Th cells. Our results suggest that the microbiome-gut-immune axis can be modified by DEHP and emphasize the value of multiomics approaches to study microbiome-host interactions following chemical perturbations.

• MeSH
• adaptivní imunita MeSH
• dánio pruhované MeSH
• diethylhexylftalát * MeSH
• kyseliny ftalové * MeSH
• lidé MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Knowledge of population exposure to phthalates based on the urinary metabolite levels is of the highest importance for health risk assessment. Such data are scarce in the Czech population. In the study conducted in 2016, six urinary phthalate metabolites were analysed in a total of 370 first morning urine samples of healthy children aged 5 and 9 years, namely mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP), mono(2-ethyl-5-oxohexyl) phthalate (5oxo-MEHP), mono-benzyl phthalate (MBzP), mono-iso-butyl phthalate (MiBP), and mono-n-butyl phthalate (MnBP). The two latter mono-butyl phthalate isoforms dominated among all samples with geometric means of 63.0 µg/L (MnBP) and 44.1 µg/L (MiBP), followed by 5OH-MEHP (20.6 µg/L), 5oxo-MEHP (12.9 µg/L), MBzP (3.65 µg/L), and MEHP (2.31 µg/L). Daily intake (DI) of the parent phthalates was estimated using the creatinine-based model. The highest DI values were found for di-n-butyl phthalate (DnBP) (median 2.5 µg/kg bw/day; 95th percentile 7.8 µg/kg bw/day) and di-2-ethylhexyl phthalate (DEHP) (median 2.3 µg/kg bw/day; 95th percentile 8.9 µg/kg bw/day) in 5-year-old children. The tolerable daily intake (TDI) set by the European Food Safety Authority (EFSA) was exceeded in case of DnBP (in 1% of 9-year-olds and in 3% of 5-year-olds). Exposure risk was assessed based on hazard quotients calculation and cumulative approach for similar health effect. The combined exposure to four phthalates expressed by hazard index (HI) for reprotoxicity revealed exceeding of HI threshold in 14% of 5-year-olds and in 9% of 9-year-olds. These findings strongly support the need to reduce the burden of children by phthalates.

• MeSH
• dávka bez pozorovaného nepříznivého účinku MeSH
• diethylhexylftalát aplikace a dávkování   analogy a deriváty   moč   MeSH
• dítě MeSH
• hodnocení rizik MeSH
• kreatinin moč   MeSH
• kyseliny ftalové aplikace a dávkování   moč   MeSH
• látky znečišťující životní prostředí aplikace a dávkování   moč   MeSH
• lidé MeSH
• předškolní dítě MeSH
• školy MeSH
• vystavení vlivu životního prostředí analýza   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

Sledování expozice látkám, široce užívaným v průmyslu, a vyhodnocení jejich koncentrací v těle člověka, je jedním z hlavních cílů biologického monitorování obyvatel. V pilotní studii byla sledována hladina metabolitů ftalátu dietylhexylftalátu (DEHP), vybraných metabolitů polyaromatických uhlovodíků a bisfenolu A v moči ve vztahu k možným expozičním zdrojům sledovaných dotazníkovým šetřením. Do studie bylo zařazeno 95 studentů nekuřáků ve věkovém rozmezí 20 až 29 let (44 mužů a 51 žen) z Prahy a Ostravy. Analyty byly stanovovány v moči pomocí metody kapalinové chromatografie s tandemovou hmotnostně-spektrometrickou detekcí typu trojitý kvadrupól (LC-MS/MS). Hodnoty metabolitů DEHP u žádného jedince nepřekročily zdravotně významné limitní hodnoty. Za pomoci dotazníku, který byl součástí studie, nebyly zjištěny žádné skutečnosti, které by významně ovlivňovaly hladiny vybraných látek v moči. Byl zjištěn pouze signifikantní vliv pohlaví u 5-OH-MEHP a sumy 5-OH-MEHP a 5-oxo-MEHP, kdy ostravské ženy mají významně vyšší hladiny metabolitů než muži.

The main target of human biomonitoring is monitoring of exposure and effects of substances used in industry and determination of their concentrations in the human body. In this pilot study the metabolite levels of phthalates, polycyclic aromatic hydrocarbons and bisphenol A were determined in urine. Their association with possible exposure sources was analyzed. The study comprised 95 adults (44 males and 51 females) aged 20 and 29 years from Prague and Ostrava. The analytes in urine samples were determined by liquid chromatography with triple quadrupole tandem mass spectrometry detection (LC-MS/MS). Metabolite levels did not exceed limit values for these biomarkers for any participant. The questionnaire survey, as part of the study, revealed no factors that might affect levels of the selected substances in urine. However, a significant gender-related difference was detected for the level of 5-OH-MEHP and sums of 5-OH-MEHP and 5-oxo-MEHP, where women from Ostrava had significantly higher metabolite values than men.

• Klíčová slova
• bisfenol A,
• MeSH
• benzhydrylové sloučeniny moč   MeSH
• biologické markery moč   MeSH
• biologický monitoring MeSH
• chromatografie kapalinová MeSH
• diethylhexylftalát * metabolismus   moč   MeSH
• dospělí MeSH
• epidemiologické monitorování MeSH
• fenoly * moč   MeSH
• kyseliny ftalové moč   MeSH
• látky znečišťující životní prostředí metabolismus   moč   MeSH
• lidé MeSH
• lineární modely MeSH
• mladý dospělý MeSH
• monitorování životního prostředí metody   statistika a číselné údaje   MeSH
• pilotní projekty MeSH
• polycyklické aromatické uhlovodíky * metabolismus   moč   MeSH
• rozložení podle pohlaví MeSH
• tandemová hmotnostní spektrometrie statistika a číselné údaje   MeSH
• vystavení vlivu životního prostředí * analýza   statistika a číselné údaje   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH

Di-(2-ethylhexyl) phthalate (DEHP) interferes with male reproductive endocrine system in mammals, however its effects on fish reproduction are largely unknown. We evaluated sperm quality and investigated reproductive endocrine system in mature goldfish (Carassius auratus) exposed to nominal 1, 10, and 100μg/L DEHP. To examine DEHP estrogenic activity, one group of goldfish was exposed to 17β-estradiol (5μg/L E2) for comparison. Following 30d of exposure, sperm production was decreased and suppressed in DEHP and E2 treated goldfish, respectively. Sperm motility and velocity were decreased in goldfish exposed to 100 and 10μg/L DEHP at 15s post-sperm activation, respectively. Compared to control, 11-ketotestosterone (11-KT) levels were decreased at 10 and 1μg/L DEHP at day 15 and 30, respectively. In E2 treated goldfish, 11-KT levels were decreased compared to control during the period of exposure. E2 levels were increased in goldfish exposed to E2, but remained unchanged in DEHP treated goldfish during the period of exposure. StAR mRNA levels encoding regulator of cholesterol transfer to steroidogenesis were decreased in DEHP and E2 treated goldfish following 15 and 30d of exposure, respectively. Luteinizing hormone (LH) levels were decreased in DEHP and E2 treated goldfish following 15 and 30d of exposure, respectively. In DEHP treated goldfish, gnrh3, kiss1 and its receptor (gpr54) mRNA levels did not change during the experimental period. In E2 treated goldfish, gnrh3 mRNA levels were decreased at day 7, but kiss1 and gpr54 mRNA levels were increased at day 30 of exposure. The mRNA levels of genes encoding testicular LH and androgen receptors remained unchanged in DEHP and E2 treated goldfish. In contrast to E2 treated goldfish, vitellogenin production was not induced in DEHP treated goldfish and mRNA levels of genes with products mediating estrogenic effects remained unchanged or decreased. In conclusion, DEHP interferes with testis and pituitary hormonal functions to reduce sperm quality in goldfish and does not exhibit estrogenic activity.

• MeSH
• androgenní receptory genetika   metabolismus   MeSH
• chemické látky znečišťující vodu chemie   toxicita   MeSH
• diethylhexylftalát toxicita   MeSH
• estradiol farmakologie   MeSH
• hormon uvolňující gonadotropiny MeSH
• hypofýza účinky léků   metabolismus   MeSH
• imunoanalýza MeSH
• karas zlatý metabolismus   MeSH
• kisspeptiny genetika   metabolismus   MeSH
• kyselina pyrrolidonkarboxylová analogy a deriváty   MeSH
• lidé MeSH
• luteinizační hormon analýza   MeSH
• messenger RNA metabolismus   MeSH
• motilita spermií účinky léků   MeSH
• receptory spřažené s G-proteiny genetika   metabolismus   MeSH
• spermie účinky léků   fyziologie   MeSH
• testis účinky léků   metabolismus   MeSH
• testosteron analogy a deriváty   analýza   MeSH
• vitelogeniny analýza   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• bezpečnost vybavení MeSH
• bisfenol A-glycidyl methakrylát normy   škodlivé účinky   toxicita   MeSH
• diethylhexylftalát normy   škodlivé účinky   toxicita   MeSH
• Evropská unie MeSH
• hodnocení rizik MeSH
• kyseliny ftalové škodlivé účinky   MeSH
• poskytování zdravotní péče MeSH
• stažení zdravotnických prostředků z trhu z bezpečnostních důvodů MeSH
• ustanovení a nařízení MeSH
• zdravotnická zařízení MeSH
• zdravotnické prostředky MeSH
• Publikační typ
• směrnice MeSH

• Konspekt
• Veřejné zdraví a hygiena
• NLK Obory
• veřejné zdravotnictví