New insight in beryllium toxicity excluding exposure to beryllium-containing dust: accumulation patterns, target organs, and elimination.

There is much contradiction between different experimental studies on beryllium (Be) toxicity. The majority of studies focus on occupational pathologies, caused by the exposure to Be dust. However, Be pollution may affect wide population groups through other exposure routes. The discrepancies between experimental studies may be attributed to the lack of adequate Be toxicity model since conventional administration routes are hampered by high acidity and low solubility of Be compounds. This study was aimed to develop a novel way to implement Be toxicity avoiding side effects, related to high acidity or low solubility of Be salts. Intraperitoneal injection of Be-glycine composition (containing BeSO4, glycine, purified water, pH adjusted to 5.5 with NaOH) was tested in the dose range 238-7622 µmol Be kg-1 (body weight, b/w) in full-grown Wistar male rats. The model provided reliable uptake of Be from the peritoneum into general circulation for at least 48 h. LD50 was found to be 687 µmol Be kg-1 (b/w). The established LD50 value differed from previous data on gastrointestinal, intramuscular or intravenous administration of Be compounds. The liver was found to act as a primary elimination route for Be and related to the highest Be content in the animal. However, it had no signs of morphological damage, which was observed only in the testes (deterioration of germinal epithelium). At the same time, the lungs, stated as a primary target tissue for Be in the models of chronic beryllium disease, did not show strong Be accumulation nor morphological changes. Survived animals showed behavioral changes, including increased motor activity and aggressive reactions in some cases, and complete spasticity in other. The obtained data show the applicability of the established modeling protocol and testified for the independence of chronic beryllium disease on Be2+ ion toxicity per se.

Selenium at the Neural Barriers: A Review.

Selenium (Se) is known to contribute to several vital physiological functions in mammals: antioxidant defense, fertility, thyroid hormone metabolism, and immune response. Growing evidence indicates the crucial role of Se and Se-containing selenoproteins in the brain and brain function. As for the other essential trace elements, dietary Se needs to reach effective concentrations in the central nervous system (CNS) to exert its functions. To do so, Se-species have to cross the blood-brain barrier (BBB) and/or blood-cerebrospinal fluid barrier (BCB) of the choroid plexus. The main interface between the general circulation of the body and the CNS is the BBB. Endothelial cells of brain capillaries forming the so-called tight junctions are the primary anatomic units of the BBB, mainly responsible for barrier function. The current review focuses on Se transport to the brain, primarily including selenoprotein P/low-density lipoprotein receptor-related protein 8 (LRP8, also known as apolipoprotein E receptor-2) dependent pathway, and supplementary transport routes of Se into the brain via low molecular weight Se-species. Additionally, the potential role of Se and selenoproteins in the BBB, BCB, and neurovascular unit (NVU) is discussed. Finally, the perspectives regarding investigating the role of Se and selenoproteins in the gut-brain axis are outlined.

Capabilities of selenoneine to cross the in vitro blood-brain barrier model.

The naturally occurring selenoneine (SeN), the selenium analogue of the sulfur-containing antioxidant ergothioneine, can be found in high abundance in several marine fish species. However, data on biological properties of SeN and its relevance for human health are still scarce. This study aims to investigate the transfer and presystemic metabolism of SeN in a well-established in vitro model of the blood-brain barrier (BBB). Therefore, SeN and the reference Se species selenite and Se-methylselenocysteine (MeSeCys) were applied to primary porcine brain capillary endothelial cells (PBCECs). Se content of culture media and cell lysates was measured via ICP-MS/MS. Speciation analysis was conducted by HPLC-ICP-MS. Barrier integrity was shown to be unaffected during transfer experiments. SeN demonstrated the lowest transfer rates and permeability coefficient (6.7 × 10-7 cm s-1) in comparison to selenite and MeSeCys. No side-directed accumulation was observed after both-sided application of SeN. However, concentration-dependent transfer of SeN indicated possible presence of transporters on both sides of the barrier. Speciation analysis demonstrated no methylation of SeN by the PBCECs. Several derivatives of SeN detected in the media of the BBB model were also found in cell-free media containing SeN and hence not considered to be true metabolites of the PBCECs. In concluding, SeN is likely to have a slow transfer rate to the brain and not being metabolized by the brain endothelial cells. Since this study demonstrates that SeN may reach the brain tissue, further studies are needed to investigate possible health-promoting effects of SeN in humans.

Selenium-rich mushrooms cultivation on a wheat straw substrate from seleniferous area in Punjab, India.

Intensive rice-wheat cultivation cycle in Northern belt of India in general and in the State of Punjab in particular results in large volumes of straw and other post-harvest residue annually. The agricultural area, bordering the districts of Nawanshahr and Hoshiarpur, is popularly known as the seleniferous belt of India. The agri-residues, generated in seleniferous region of this state, are observed to contain significantly high concentration of selenium (Se). The present study was aimed to evaluate the Se uptake by different mushroom species: Pleurotus sajor-caju, Pleurotus ostreatus, Pleurotus citrinopileatus, Agaricus bisporus, and Volvariella volvacea, cultivated on Se-rich wheat and paddy straw from the seleniferous region. Wheat (Pleurotus species and A. bisporus) and paddy straw (V. volvacea) was inoculated with the mycelium spawn and left for 7-20 days, depending on the species, to grow. Control mushrooms were grown analogously using the agricultural residues from non-seleniferous area of the State of Punjab. All fruiting bodies were collected and analyzed in triplicate. Se was quantified using inductively coupled plasma sector field mass spectrometry. The Se accumulation was high in all species under study, being the highest in A. bisporus (1396 µg/g vs. 46.8 µg/g in controls - dry weight) and V. volvacea (231 µg/g vs. 3.77 µg/g - dry weight). The observed biological efficiency and total yield for all mushroom species showed good and unaltered productivity in Se-rich conditions, if compared to the controls. The Se-rich mushrooms can be prospective Se-supplements sourcing and biofortified foods, providing readily bioavailable and accessible Se for the diets deficient of this biologically essential element.

Accumulation Patterns of Sub-chronic Aluminum Toxicity Model After Gastrointestinal Administration in Rats.

Although aluminum chronic neurotoxicity is well documented, there are no well-established experimental protocols of Al exposure. In the current study, toxic effects of sub-chronic Al exposure have been evaluated in outbreed male rats (gastrointestinal administration). Forty animals were used: 10 were administered with AlCl3 water solution (2 mg/kg Al per day) for 1 month, 10 received the same concentration of AlCl3 for 3 month, and 20 (10 per observation period) saline as control. After 30 and 90 days, the animals underwent behavioral tests: open field, passive avoidance, extrapolation escape task, and grip strength. At the end of the study, the blood, liver, kidney, and brain were excised for analytical and morphological studies. The Al content was measured by inductively coupled plasma mass-spectrometry. Essential trace elements-Co, Cr, Cu, Fe, Mg, Mn, Mo, Se, and Zn-were measured in whole blood samples. Although no morphological changes were observed in the brain, liver, or kidney for both exposure terms, dose-dependent Al accumulation and behavioral differences (increased locomotor activity after 30 days) between treatment and control groups were indicated. Moreover, for 30 days exposure, strong positive correlation between Al content in the brain and blood for individual animals was established, which surprisingly disappeared by the third month. This may indicate neural barrier adaptation to the Al exposure or the saturation of Al transport into the brain. Notably, we could not see a clear neurodegeneration process after rather prolonged sub-chronic Al exposure, so probably longer exposure periods are required.

Selenium, selenoprotein P, and Alzheimer's disease: is there a link?

The essential trace element, selenium (Se), is crucial to the brain but it may be potentially neurotoxic, depending on dosage and speciation; Se has been discussed for decades in relation to Alzheimer's disease (AD). Selenoprotein P (SELENOP) is a secreted heparin-binding glycoprotein which serves as the main Se transport protein in mammals. In vivo studies showed that this protein might have additional functions such as a contribution to redox regulation. The current review focuses on recent research on the possible role of SELENOP in AD pathology, based on model and human studies. The review also briefly summarizes results of epidemiological studies on Se supplementation in relation to brain diseases, including PREADViSE, EVA, and AIBL. Although mainly positive effects of Se are assessed in this review, possible detrimental effects of Se supplementation or exposure, including potential neurotoxicity, are also mentioned. In relation to AD, various roles of SELENOP are discussed, i.e. as the means of Se delivery to neurons, as an antioxidant, in cytoskeleton assembly, in interaction with redox-active metals (copper, iron, and mercury) and with misfolded proteins (amyloid-beta and hyperphosphorylated tau-protein).

Trace element biomonitoring in hair of school children from a polluted area by sector field inductively coupled plasma mass spectrometry.

In the current study, a biomonitoring of 18 hair trace elements (Al, As, Cd, Co, Cr, Cu, Fe, Hg, Mg, Mn, Ni, Pb, Se, V, Zn, Ca, Na and P) in school children from Leningradskaya Oblast' is reported. A case group, residing in a proximity to the toxic waste disposal grounds (Krasniy Bor), has been assessed vs. controls from a non-urban settlement Seltso. In total, 166 hair samples were analysed using double focusing sector field inductively coupled plasma mass spectrometry after microwave-assisted sample digestion with nitric acid. For the determination of Ca, Na and P inductively coupled plasma optical emission spectrometry was employed. For the validation, a reference material and spiked hair samples were analysed. The data obtained was processed using parametric statistics and factor analysis. Determined concentrations of trace elements were in agreement with the previously published results on chemically polluted areas. In the case group, linear correlations between Al, Cr, Cu, Fe, Ni and V were observed. Also, these metals correlated to selenium hair content in the case group. Additionally, a correlation between hair Se and P was observed in the case subjects. Several gender differences in trace content were observed within each group. However, no age- or body index-related difference was found. The obtained results show that closely located waste disposal grounds intensifies trace element exposure in school children of Krasniy Bor. However, judging from rather high values for the controls, total environmental status of the region seems to be unstable, so additional monitoring and chemical safety measures are required.

Anticancer activity and tissue distribution of platinum (II) complex with lignin-derived polymer of benzene-poly-carboxylic acids.

Platinum-containing antineoplastic agents with physiologically active ligands seem to be a promising direction in anticancer drug design. PDBA is a novel promising antineoplastic agent, containing polymer ligand of natural origin (international patent WO2013/143549 A1). Polymer ligand of PDBA has a highly functionalised polyphenolic backbone, which exerts its own pharmacological effect via immune modulation and regulation of gene expression. PDBA is a cis-diammineplatinum(II) complex, containing mono-deprotonated benzene-poly-carboxylic acids, derived from lignin, and hydroxyl group as O-donor ligands (approximate bulk formula C83H70N2O27Pt). The agent is being evaluated in Phase II controlled clinical trials in metastatic breast cancer patients. In the present study, tissue distribution and tumour growth inhibition effects of PDBA, cisplatin and carboplatin were compared in SHR female mice, bearing inoculated solid Ehrlich carcinoma. The agents were administered subcutaneously every second day for the period of 10days (5 injections) at 62.5mg/kg, 3.0mg/kg and 18.5mg/kg for PDBA, cisplatin and carboplatin, respectively. Experimental animals were sacrificed on the Days 11, 16 and 23 after the inoculation of the tumour. The doses of all studied drugs were selected to obtain similar antitumour efficacy with ca. 50% growth inhibition of the Ehrlich tumour at the end of the study. The efficacy of a single platinum reactive moiety [cis-diammineplatinum(II)] was shown to be the highest for cisplatin, followed by PDBA and finally carboplatin. However, the toxicity of PDBA was considerably lower than that of carboplatin and especially cisplatin. The drugs were mainly distributed in lungs, kidneys, liver, spleen and tumour tissue. PDBA showed quite high accumulation in the tumour tissue, possibly, owing to the effect of the lignin-derived ligand.