Refine
Has Fulltext
- no (18) (remove)
Language
- English (18)
Is part of the Bibliography
- yes (18)
Keywords
- arsenolipids present (2)
- cod-liver (2)
- fatty-acids (2)
- identification (2)
- manganese (2)
- Antioxidant (1)
- BeWo b30 (1)
- Biochemistry (1)
- Biological Sciences (1)
- Biomarker (1)
Institute
- Institut für Chemie (18) (remove)
Boric acid and sodium borates are currently classified in the EU-CLP regulation as "toxic to reproduction" under "Category 1B", with hazard statement of H360FD. However, so far field studies on male reproduction in China and in Turkey could not confirm such boron-associated toxic effects. As validation by another independent study is still required, the present study has investigated possible boron-associated effects on male reproduction in workers (n = 212) under different boron exposure conditions. The mean daily boron exposure (DBE) and blood boron concentration of workers in the extreme exposure group (n = 98) were 47.17 +/- 17.47 (7.95-106.8) mg B/day and 570.6 +/- 160.1 (402.6-1100) ng B/g blood, respectively. Nevertheless, boron-associated adverse effects on semen parameters, as well as on FSH, LH and total testosterone levels were not seen, even within the extreme exposure group. With this study, a total body of evidence has accumulated that allows to conclude that male reproductive effects are not relevant to humans, under any feasible and realistic conditions of exposure to inorganic boron compounds.
Arsenic-containing hydrocarbons are one group of fat-soluble organic arsenic compounds (arsenolipids) found in marine fish and other seafood. A risk assessment of arsenolipids is urgently needed, but has not been possible because of the total lack of toxicological data. In this study the cellular toxicity of three arsenic-containing hydrocarbons was investigated in cultured human bladder (UROtsa) and liver (HepG2) cells. Cytotoxicity of the arsenic-containing hydrocarbons was comparable to that of arsenite, which was applied as the toxic reference arsenical. A large cellular accumulation of arsenic, as measured by ICP-MS/MS, was observed after incubation of both cell lines with the arsenolipids. Moreover, the toxic mode of action shown by the three arsenic-containing hydrocarbons seemed to differ from that observed for arsenite. Evidence suggests that the high cytotoxic potential of the lipophilic arsenicals results from a decrease in the cellular energy level. This first in vitro based risk assessment cannot exclude a risk to human health related to the presence of arsenolipids in seafood, and indicates the urgent need for further toxicity studies in experimental animals to fully assess this possible risk.
This study aims to further mechanistically understand toxic modes of action after chronic inorganic arsenic exposure. Therefore long-term incubation studies in cultured cells were carried out, to display chronically attained changes, which cannot be observed in the generally applied in vitro short-term incubation studies. Particularly, the cytotoxic, genotoxic and epigenetic effects of an up to 21 days incubation of human urothelial (UROtsa) cells with pico- to nanomolar concentrations of iAsIII and its metabolite thio-DMAV were compared. After 21 days of incubation, cytotoxic effects were strongly enhanced in the case of iAsIII and might partly be due to glutathione depletion and genotoxic effects on the chromosomal level. These results are in strong contrast to cells exposed to thio-DMAV. Thus, cells seemed to be able to adapt to this arsenical, as indicated among others by an increase in the cellular glutathione level. Most interestingly, picomolar concentrations of both iAsIII and thio-DMAV caused global DNA hypomethylation in UROtsa cells, which was quantified in parallel by 5-medC immunostaining and a newly established, reliable, high resolution mass spectrometry (HRMS)-based test system. This is the first time that epigenetic effects are reported for thio-DMAV; iAsIII induced epigenetic effects occur in at least 8000 fold lower concentrations as reported in vitro before. The fact that both arsenicals cause DNA hypomethylation at really low, exposure-relevant concentrations in human urothelial cells suggests that this epigenetic effect might contribute to inorganic arsenic induced carcinogenicity, which for sure has to be further investigated in future studies.
Arsenic-containing fatty acids are a group of fat-soluble arsenic species (arsenolipids) which are present in marine fish and other seafood. Recently, it has been shown that arsenic-containing hydrocarbons, another group of arsenolipids, exert toxicity in similar concentrations comparable to arsenite although the toxic modes of action differ. Hence, a risk assessment of arsenolipids is urgently needed. In this study the cellular toxicity of a saturated (AsFA 362) and an unsaturated (AsFA 388) arsenic-containing fatty acid and three of their proposed metabolites (DMAV, DMAPr and thio-DMAPr) were investigated in human liver cells (HepG2). Even though both arsenic-containing fatty acids were less toxic as compared to arsenic-containing hydrocarbons and arsenite, significant effects were observable at μM concentrations. DMAV causes effects in a similar concentration range and it could be seen that it is metabolised to its highly toxic thio analogue thio-DMAV in HepG2 cells. Nevertheless, DMAPr and thio-DMAPr did not exert any cytotoxicity. In summary, our data indicate that risks to human health related to the presence of arsenic-containing fatty acids in marine food cannot be excluded. This stresses the need for a full in vitro and in vivo toxicological characterisation of these arsenolipids.
Arsenolipids, especially arsenic-containing hydrocarbons (AsHC), are an emerging class of seafood originating contaminants. Here we toxicologically characterize a recently identified oxo-AsHC 332 metabolite, thioxo-AsHC 348 in cultured human liver (HepG2) cells. Compared to results of previous studies of the parent compound oxo-AsHC 332, thioxo-AsHC 348 substantially affected cell viability in the same concentration range but exerted about 10-fold lower cellular bioavailability. Similar to oxo-AsHC 332, thioxo-AsHC 348 did not substantially induce oxidative stress nor DNA damage. Moreover, in contrast to oxo-AsHC 332 mitochondria seem not to be a primary subcellular toxicity target for thioxo-AsHC 348. This study indicates that thioxo-AsHC 348 is at least as toxic as its parent compound oxo-AsHC 332 but very likely acts via a different mode of toxic action, which still needs to be identified.
Selenoneine, a naturally occurring form of selenium, is the selenium analogue of ergothioneine, a sulfur species with health relevance not only as a purported antioxidant but likely also beyond. Selenoneine has been speculated to exhibit similar effects. To study selenoneine's health properties as well as its metabolic transformation, the pure compound is required. Chemical synthesis of selenoneine, however, is challenging and biosynthetic approaches have been sought. We herein report the biosynthesis and isolation of selenoneine from genetically modified fission yeast Schizosaccharomyces pombe grown in a medium containing sodium selenate. After cell lysis and extraction with methanol, selenoneine was purified by three consecutive preparative reversed-phase HPLC steps. The product obtained at the mg level was characterised by high resolution mass spectrometry, NMR and HPLC/ICPMS. Biosynthesis was found to be a promising alternative to chemical synthesis, and should be suitable for upscaling to produce higher amounts of this important selenium species in the future.
Selenoneine and ergothioneine in human blood cells determined simultaneously by HPLC/ICP-QQQ-MS
(2019)
The possible relevance to human health of selenoneine and its sulfur-analogue ergothioneine has generated interest in their quantitative determination in biological samples. To gain more insight into the similarities and differences of these two species, a method for their simultaneous quantitative determination in human blood cells using reversed-phase high performance liquid chromatography (RP-HPLC) coupled to inductively coupled plasma triple quadrupole mass spectrometry (ICP-QQQ-MS) is presented. Spectral interferences hampering the determination of sulfur and selenium by ICPMS are overcome by introducing oxygen to the reaction cell. To access selenoneine and ergothioneine in the complex blood matrix, lysis of the cells with cold water followed by cut-off filtration (3000 Da) is performed. Recoveries based on blood cells spiked with selenoneine and ergothioneine were between 80% and 85%. The standard deviation of the method was around 0.10 mg S per L for ergothioneine (corresponding to relative standard deviations (RSD) between 10-1% for ergothioneine concentrations of 1-10 mg S per L) and 0.25 g Se per L for selenoneine (RSDs of 25-2% for concentrations of 1-10 g Se per L). The method was applied to blood cell samples from three volunteers which showed selenoneine and ergothioneine concentrations in the range of 3.25 to 7.35 g Se per L and 0.86 to 6.44 mg S per L, respectively. The method is expected to be of wide use in future studies investigating the dietary uptake of selenoneine and ergothioneine and their relevance in human health.
Here, a reliable and sensitive method for the determination of 38 (modified) mycotoxins was developed. Using a QuEChERS-based extraction method [acetonitrile/water/formic acid (75:20:5, v/v/v)], followed by two runs of high performance liquid chromatography tandem mass spectrometry with different conditions, relevant mycotoxins in cereals were analyzed. The method was validated according to the performance criteria defined by the European Commission (EC) in Commission Decision no. 657/2002. Limits of quantification ranged from 0.05 to 150 μg/kg. Good linearity (R2 > 0.99), recovery (61–120%), repeatability (RSDr < 15%), and reproducibility (RSDR < 20%) were obtained for most mycotoxins. However, validation results for Alternaria toxins and fumonisins were unsatisfying. Matrix effects (−69 to +59%) were compensated for using standard addition. Application on reference materials gave correct results while analysis of samples from local retailers revealed contamination, especially with deoxynivalenol, deoxynivalenol-3-glucoside, fumonisins, and zearalenone, in concentrations up to 369, 58, 1002, and 21 μg/kg, respectively.
Scope: Trace element (TE) deficiencies often occur accumulated, as nutritional intake is inadequate for several TEs, concurrently. Therefore, the impact of a suboptimal supply of iron, zinc, copper, iodine, and selenium on the TE status, health parameters, epigenetics, and genomic stability in mice are studied. Methods and results: Male mice receive reduced or adequate amounts of TEs for 9 weeks. The TE status is analyzed mass‐spectrometrically in serum and different tissues. Furthermore, gene and protein expression of TE biomarkers are assessed with focus on liver. Iron concentrations are most sensitive toward a reduced supply indicated by increased serum transferrin levels and altered hepatic expression of iron‐related genes. Reduced TE supply results in smaller weight gain but higher spleen and heart weights. Additionally, inflammatory mediators in serum and liver are increased together with hepatic genomic instability. However, global DNA (hydroxy)methylation is unaffected by the TE modulation. Conclusion: Despite homeostatic regulation of most TEs in response to a low intake, this condition still has substantial effects on health parameters. It appears that the liver and immune system react particularly sensitive toward changes in TE intake. The reduced Fe status might be the primary driver for the observed effects.
Hazelnuts are rarely cultivated in Germany, although they are a valuable source for macro- and micronutrients and can thus contribute to a healthy diet. Near the present, 15 varieties were cultivated in Thuringia, Germany, as a pilot study for further research. The aim of our study was to evaluate the micro- and macronutrient composition of representative, randomly mixed samples of the 15 different hazelnut cultivars. Protein, fat, and fiber contents were determined using established methods. Fatty acids, tocopherols, minerals, trace elements, and ultra-trace elements were analyzed using gas chromatography, high-performance liquid chromatography, and inductively coupled plasma triple quadrupole mass-spectrometry, respectively. We found that the different hazelnut varieties contained valuable amounts of fat, protein, dietary fiber, minerals, trace elements, and alpha-tocopherol, however, in different quantities. The variations in nutrient composition were independent of growth conditions, which were identical for all hazelnut varieties. Therefore, each hazelnut cultivar has its specific nutrient profile.