Sensitive analysis of very low-molecular weight metabolites using liquid chromatography with quadrupole-time-of-flight mass spectrometry is challenging due to the high losses of ions in a time-of-flight analyzer. Improvement in sensitivity for these analytes via the optimization of advanced parameters, including quadrupole profile, ion guide parameters, and duty cycle, has been achieved. The optimization of the method was carried out using a large spectrum of structurally different compounds including (iso)flavonoids and their known metabolites. These compounds can be categorized into two major groups, that is, compounds with (iso)flavonoid core and low-molecular weight phenolics. The optimization of the duty cycle enabled up to a 15-fold increase in analyte responses while the contribution of tuning ion optics and quadrupole profile was negligible. The limits of quantifications of our new method were assessed using both standard solutions and rat plasma. They were decreased at least 10 times for several low-molecular weight phenolics enabling measurement of their concentrations in a range of 1-50 ng/mL in rat plasma after protein precipitation. Concurrently, the limits of quantifications for compounds with (iso)flavonoid core did not increase distinctly allowing their detection in a range of 0.5-10 ng/mL. The new method was used for the targeting of phenolics in biological samples from pharmacokinetics experiments.
After menopause, when estrogen levels decrease, there is room for the activity of anthropogenic substances with estrogenic properties - endocrine disruptors (EDs) - that can interfere with bone remodeling and changes in calcium-phosphate metabolism. Selected unconjugated EDs of the bisphenol group - BPA, BPS, BPF, BPAF, and the paraben family - methyl-, ethyl-, propyl-, butyl-, and benzyl-parabens - were measured by high performance liquid chromatography-tandem mass spectrometry in the plasma of 24 postmenopausal women. Parameters of calcium-phosphate metabolism and bone mineral density were assessed. Osteoporosis was classified in 14 women, and 10 women were put into the control group. The impact of EDs on calcium-phosphate metabolism was evaluated by multiple linear regressions. In women with osteoporosis, concentrations of BPA ranged from the lower limit of quantification (LLOQ) - 104 pg/ml and methyl paraben (MP) from LLOQ - 1120 pg/ml. The alternative bisphenols BPS, BPF and BPAF were all under the LLOQ. Except for MP, no further parabens were detected in the majority of samples. The multiple linear regression model found a positive association of BPA (beta=0.07, p<0.05) on calcium (Ca) concentrations. Furthermore, MP (beta=-0.232, p<0.05) was negatively associated with C-terminal telopeptide. These preliminary results suggest that these EDs may have effects on calcium-phosphate metabolism.
- MeSH
- absorpční fotometrie metody MeSH
- benzhydrylové sloučeniny škodlivé účinky krev MeSH
- endokrinní disruptory škodlivé účinky krev MeSH
- fenoly škodlivé účinky krev MeSH
- kostní denzita účinky léků fyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- parabeny škodlivé účinky metabolismus MeSH
- postmenopauzální osteoporóza krev chemicky indukované diagnostické zobrazování MeSH
- remodelace kosti účinky léků fyziologie MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
In this study, a novel liquid chromatography - tandem mass spectrometry method for the simultaneous determination of bisphenols (BPA, BPS, BPF, BPAF), parabens (methyl-, ethyl-, propyl-, butyl-, benzyl-paraben) and estrogens (estrone, estradiol, estriol) in human plasma is presented. Since all analytes possess the phenolic group, dansyl chloride derivatization was applied in order to gain high sensitivity. The method was validated according to FDA guidelines, and all validation requirements were satisfactory. The lower limits of quantifications were 41.6, 54.9, 43.5 and 150.8pg/mL for BPA, BPS, BPF and BPAF; 172, 149, 171, 134 and 202pg/mL for methyl-, ethyl-, propyl-, butyl- and benzyl-paraben; 10.5, 6.7 and 9.4pg/mL for estrone, estradiol and estriol, respectively. This is the first method allowing the determination of plasma bisphenols, parabens and estrogens in one run, and also the first determination of BPF levels in human plasma. The method was used to examine the plasma levels of healthy normospermic men, where three times higher plasma levels of BPF than BPA were found.
- MeSH
- biochemická analýza krve metody MeSH
- chromatografie kapalinová MeSH
- estrogeny krev MeSH
- fenoly krev MeSH
- lidé MeSH
- limita detekce MeSH
- parabeny analýza MeSH
- tandemová hmotnostní spektrometrie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: In the testis, steroid hormones play an important role in spermatogenesis, the production of semen, and the maintenance of secondary sex characteristics and libido. They may also play a role as a target for substances called endocrine disruptors (EDs). As yet, however, no complex study has been conducted evaluating the relationships between EDs and the steroid spectrum in the plasma and seminal plasma. OBJECTIVES: To shed more light into mechanisms of EDs and the effects of bisphenol A (BPA) and polychlorinated biphenyls (PCBs) on human spermatogenesis and steroidogenesis. METHODS: We determined BPA and 11 steroids in the plasma and seminal plasma of 191 men with different degrees of fertility, using a newly developed liquid-chromatography mass spectrometry method. Concurrently, plasma levels of 6 congeners of PCBs, gonadotropins, selenium, zinc and homocysteine were measured. Partial correlations adjusted for age, BMI and abstinence time were performed to evaluate relationships between these analytes. RESULTS: Seminal BPA, but not plasma BPA, was negatively associated with sperm concentration (r=-0.198; p=0.009), sperm count (r=-0.178; p=0.018) and morphology (r=-0.160; p=0.044). Divergent and sometimes opposing associations of steroids and BPA were found in both body fluids. The sum of PCB congeners was negatively associated with testosterone, free testosterone, the free androgen index and dihydrotestosterone in plasma. CONCLUSION: BPA may negatively contribute to the final state of sperm quality. Moreover, our data indicate that BPA influences human gonadal and adrenal steroidogenesis at various steps. Environmental levels of PCBs negatively correlated with androgen levels, but surprisingly without negative effects on sperm quality.
- MeSH
- benzhydrylové sloučeniny analýza krev toxicita MeSH
- chromatografie kapalinová metody MeSH
- dospělí MeSH
- endokrinní disruptory analýza krev toxicita MeSH
- fenoly analýza krev toxicita MeSH
- lidé MeSH
- mužská infertilita krev chemicky indukované epidemiologie MeSH
- počet spermií MeSH
- pohlavní steroidní hormony krev MeSH
- polychlorované bifenyly analýza krev toxicita MeSH
- sperma chemie účinky léků MeSH
- spermatogeneze účinky léků MeSH
- spermie chemie účinky léků patologie MeSH
- testosteron krev MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The general population is potentially exposed to many chemicals that can affect the endocrine system. These substances are called endocrine disruptors (EDs), and among them bisphenol A (BPA) is one of the most widely used and well studied. Nonetheless, there are still no data on simultaneous measurements of various EDs along with steroids directly in the seminal fluid, where deleterious effects of EDs on spermatogenesis and steroidogenesis are assumed. We determined levels of BPA and 3 estrogens using LC-MS/MS in the plasma and seminal plasma of 174 men with different degrees of infertility. These men were divided according their spermiogram values into 4 groups: (1) healthy men, and (2) slightly, (3) moderate, and (4) severely infertile men. Estradiol levels differed across the groups and body fluids. Slightly infertile men have significantly higher BPA plasma and seminal plasma levels in comparison with healthy men (p<0.05 and p<0.01, respectively). Furthermore, seminal BPA, but not plasma BPA, was negatively associated with sperm concentration and total sperm count (-0.27; p<0.001 and -0.24; p<0.01, respectively). These findings point to the importance of seminal plasma in BPA research. Overall, a disruption of estrogen metabolism was observed together with a weak but significant impact of BPA on sperm count and concentration.
- MeSH
- benzhydrylové sloučeniny krev metabolismus MeSH
- biologické markery krev metabolismus MeSH
- dospělí MeSH
- estrogeny krev metabolismus MeSH
- fenoly krev metabolismus MeSH
- lidé MeSH
- mužská infertilita krev diagnóza metabolismus MeSH
- počet spermií metody MeSH
- sperma metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Bisphenol A (BPA) is a widely known endocrine disruptor with estrogenic, antiestrogenic or antiandrogenic properties. BPA could interfere with estrogen metabolism as well with receptor-mediated estrogen actions. Both environmental BPA and estrogens may be traced in body fluids, of which, besides the blood plasma, the seminal fluid is of particular interest regarding their possible interactions in the testis. The method for simultaneously determining BPA and estrogens is then needed, taking into account that their concentrations in these body fluid may differ. Here the method was developed and validated for measurements of BPA, estrone (E1), estradiol (E2) and estriol (E3) in blood plasma and seminal plasma using liquid chromatography-tandem mass spectrometry. Due to the phenolic moiety of all compounds, dansyl chloride derivatization could be used. The analytical criteria of the method with respect to expected concentration of the analytes were satisfactory. The lower limits of quantifications (LLOQ) amounted to 43.5, 4.0, 12.7, 6.7 pg/mL for plasma BPA, E1, E2 and E3, and 28.9, 4.9, 4.5, 3.4 pg/mL for seminal BPA, E1, E2 and E3, respectively. The concentrations of individual steroids differed between body fluids. To the best of our knowledge, this is the first method that enabled the measurement of estrogens and BPA together in one run. The concentrations of E1, E2 and for the first time also of E3 in seminal plasma in normospermic men are reported.
- MeSH
- benzhydrylové sloučeniny analýza krev MeSH
- chromatografie kapalinová metody MeSH
- endokrinní disruptory analýza krev MeSH
- estrogeny analýza krev MeSH
- estron analýza krev MeSH
- fenoly analýza krev MeSH
- lidé MeSH
- limita detekce MeSH
- sperma chemie MeSH
- tandemová hmotnostní spektrometrie metody MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- validační studie MeSH
The aim of this study was to assess the influence of regular daily consumption of white wine on oxidative stress and cardiovascular risk markers. Forty-two healthy male volunteers consumed 375 ml of white wine daily. Each participant provided three venous blood samples (before wine consumption, following the wine consumption period and again a month later). Levels of superoxide dismutase, glutathione peroxidase, reduced glutathione, total antioxidant capacity, total cholesterol, HDL-cholesterol, apolipoprotein A I, apolipoprotein B, triglycerides, paraoxonase 1, C-reactive protein, homocysteine, thiobarbituric acid reactive substances (TBARS) and advanced oxidation protein products (AOPP) were measured. Immediately following the month of white wine consumption there was a significant increase in HDL-cholesterol (p<0.0001), paraoxonase 1 (p<0.001), glutathione peroxidase (p<0.001) and reduced glutathione (p<0.01) levels, a decrease in superoxide dismutase activities (p<0.0001), and a decrease in oxidation protein products (p<0.001) and TBARS (p<0.05) concentrations. However, there was also a clear increase in homocysteine (p<0.0001) after a month of white wine consumption. The results of our non-placebo controlled trial suggest that regular daily white wine consumption is associated not only with both antioxidative and antiatherogenic effects but also with a potentially proatherogenic increase of homocysteine concentrations.
- MeSH
- antioxidancia fyziologie metabolismus MeSH
- fenoly farmakokinetika krev metabolismus MeSH
- finanční podpora výzkumu jako téma MeSH
- homocystein krev metabolismus škodlivé účinky MeSH
- inhibitory agregace trombocytů farmakokinetika metabolismus MeSH
- kardiovaskulární systém metabolismus účinky léků MeSH
- lidé MeSH
- oxidační stres genetika účinky záření MeSH
- víno analýza využití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- klinické zkoušky MeSH
- MeSH
- analýza potravin MeSH
- fenoly chemie krev metabolismus MeSH
- nádory prevence a kontrola MeSH
- nemoc prevence a kontrola MeSH
- ovoce MeSH
- zelenina MeSH
- Publikační typ
- přehledy MeSH
34 s. ; 18 cm
- MeSH
- dialýza ledvin MeSH
- dospělí MeSH
- draslík aplikace a dávkování MeSH
- extracelulární prostor chemie metabolismus MeSH
- fenoly farmakokinetika krev MeSH
- hemoglobiny analýza metabolismus MeSH
- kompartmenty tělních tekutin genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- uremie krev terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
