Nutraceuticals as Potential Radionuclide Decorporation Agents.

Exposure of individuals to radioactive material as a result of ingestion of contaminated food and water is an increasing public health concern. Unfortunately, there are limited treatment modalities for dealing with these types of potentially toxic exposures. Recent research suggests that many plant-based nutraceuticals may possess metal-binding properties. This preliminary study investigated the ability of genistein, curcumin, quercetin, and lentinan to bind metals considered internal contamination risks, namely cesium, uranium, cobalt, and strontium, in a variety of matrices. The efficacy of these nutraceuticals in protecting cultured cells from metal-induced toxicity was also explored. Results showed that none of the compounds bound cesium or strontium. However, genistein, curcumin, and quercetin could bind uranium. Curcumin and quercetin also bound cobalt and could also protect cultured cells from metal-induced cytotoxicity. Lentinan did not bind any of the metals tested. Metal binding was also pH dependent, with no binding observed at lower pH values. This project showed that nutraceuticals could function as chelators for metals considered internal radionuclide contamination hazards. Further investigations are required in order to determine whether these compounds will become a new nontoxic arsenal of pharmaceutical compounds with which to treat radionuclide contamination.

Evaluation of the Neurotoxicity of Strontium and Glycyrrhiza Glabra: First Report.

AIM: To investigate the neurotoxic effects of strontium (Sr) compounds and Glycyrrhiza glabra (licorice, G. glabra). MATERIAL AND METHODS: In this study, we conducted neurotoxicity assays on the human cortical neuronal cell line HCN-2 (CRL- 10742) to determine the potential neurotoxic effects of Sr and G. glabra. RESULTS: No significant decrease in HCN-2 cell viability was observed with longer Sr exposure or Sr concentrations up to 2000 ?g/mL. The IC < sub > 50 < /sub > values of Sr for 24 and 48 hours of exposure were > 2000 ?g/mL, and 936.9 ± 0.09 ?g/mL for 72 hours. However, we observed a significant reduction in HCN-2 cell viability with longer exposure and higher concentrations of G. glabra. The IC < sub > 50 < /sub > values of G. glabra for 24, 48, and 72 hours were 545.1 ± 0.03 ?g/mL, 398.1 ± 0.03 ?g/mL, and 393.3 ± 0.02 ?g/mL, respectively. CONCLUSION: Additional studies are needed to further investigate the neurotoxicity of Sr and G. glabra, and elucidate the pathway by which these compounds exert their therapeutic effects in pathological conditions.

Toxicity assessment of artificially added zinc, selenium, and strontium in water.

The present research was to study the toxicology of artificially added Zn, Se and Sr in water. Specifically, we investigated the mortality and liver toxicity in zebrafish (Danio rerio), caused by different water concentrations of zinc sulfate (ZnSO4), sodium selenite (Na2SeO3), and strontium chloride hexahydrate (6H2O·SrCl2). Adult and embryo-larval zebrafish were used in the experiment. Analysis was performed of mortality, liver area and impermeability, delayed absorption area of the yolk sac, and liver tissue structure. The concentration change of sodium selenite exerted the most significant effect on the mortality of adult zebrafish, followed by that of strontium chloride hexahydrate, and zinc sulfate. Elevated strontium chloride hexahydrate concentration was associated with liver toxicity in zebrafish in the preliminary experiment. However, embryo-larval zebrafish were observed to die when the concentration of Zn2+ or Se4+ increased to a certain extent, without obvious liver toxicity. Our results indicated strontium chloride hexahydrate was hepatotoxic to embryo-larval zebrafish, which was manifested mainly as hepatomegaly and delayed absorption of the yolk sac. In addition, the artificially added strontium chloride hexahydrate destroyed liver tissue structure, resulting in hepatocyte enlargement, cell nucleus enlargement, blurred cytoplasmic boundaries, and formation of a vacuolar liver. These findings suggest the amount of strontium chloride hexahydrate added in soft drinks should be limited to certain levels.

Effect of Long-Term Strontium Exposure on the Content of Phytoestrogens and Allantoin in Soybean.

Abiotic stress, including metal excess, can modify plant metabolism. Here we investigated the influence of long-term strontium exposure (12 weeks, 0.5⁻4.0 mM Sr) on the content of phytoestrogens and allantoin as well as the mineral composition in soybean. Seven phytoestrogens were identified in the soybean: daidzin, glycitin, genistin, malonyldaidzin, malonylgenistin, daidzein, and coumestrol. The results showed that both malonyldaidzin and malonylgenistin were dominant phytoestrogens; however, the roots contained a relatively high amount of daidzein. It was found that strontium reduced the phytoestrogen content and decreased the antioxidant capacity. Strontium evoked depletion of the sum of all phytoestrogens by 40⁻70% in the leaves, 25⁻50% in the stems and in the seeds, depending on the strontium concentration. In the roots, 0.5 and 4.0 mM of strontium decreased the total phytoestrogen content by 25 and 55%, respectively, while 2.0 mM of strontium did not exert an effect on their accumulation. On the other hand, strontium ions induced allantoin accumulation mainly in the roots. Strontium was preferentially accumulated in the leaves, with a slight impact on macro- and micro-nutrients. Our research showed strontium-secondary metabolites interaction in the soybean, which can be useful for obtaining a natural pharmaceutical product containing both strontium and phytoestrogens for remediation of postmenopausal osteoporosis.

Association of soil selenium, strontium, and magnesium concentrations with Parkinson's disease mortality rates in the USA.

Among the 41 soil elements analyzed from 4856 sites across the contiguous 48 states, average Parkinson's disease (PD) mortality rates between 1999 and 2014 have the most significant positive correlation with the average soil strontium (Sr) concentrations (correlation r = 0.47, significance level p = 0.00), and average PD mortality rates have the most significant inverse correlation with the average soil selenium (Se) concentrations (r = -0.44, p = 0.00). Multivariate regression models indicate that soil Sr and Se concentrations can explain 35.4% of spatial disparities of the state average PD mortality rates between 1999 and 2014 (R 2 = 0.354). When the five outlier states were removed from the model, concentrations of soil Sr and Se can explain 62.4% (R 2 = 0.624) of the spatial disparities of PD mortality rates of the 43 remaining states. The results also indicate that high soil magnesium (Mg) concentrations suppressed the growth rate of the PD mortality rates between 1999 and 2014 in the 48 states (r = -0.42, p = 0.000). While both Se and Sr have been reported to affect the nervous system, this study is the first study that reported the statistically significant association between the PD mortality rates and soil concentrations of Se, Sr, and Mg in the 48 states. Given that soil elemental concentration in a region is broad indicator of the trace element intake from food, water, and air by people, implications of the results are that high soil Se and Mg concentrations helped reduce the PD mortality rates and benefited the PD patients in the 48 states.

Chronic exposure to low concentrations of strontium 90 affects bone physiology but not the hematopoietic system in mice.

The aim of this work was to delineate the effects of chronic ingestion of strontium 90 ((90) Sr) at low concentrations on the hematopoiesis and the bone physiology. A mouse model was used for that purpose. Parent animals ingested water containing 20 kBq l(-1) of (90) Sr two weeks before mating. Offspring were then continuously contaminated with (90) Sr through placental transfer during fetal life, through lactation after birth and through drinking water after weaning. At various ages between birth and 20 weeks, animals were tested for hematopoietic parameters such as blood cell counts, colony forming cells in spleen and bone marrow and cytokine concentrations in the plasma. However, we did not find any modification in (90) Sr ingesting animals as compared with control animals. By contrast, the analysis of bone physiology showed a modification of gene expression towards bone resorption. This was confirmed by an increase in C-telopeptide of collagen in the plasma of (90) Sr ingesting animals as compared with control animals. This modification in bone metabolism was not linked to a modification of the phosphocalcic homeostasis, as measured by calcium, phosphorus, vitamin D and parathyroid hormone in the blood. Overall these results suggest that the chronic ingestion of (90) Sr at low concentration in the long term may induce modifications in bone metabolism but not in hematopoiesis.

Radio frequency induced hyperthermia mediated by dextran stabilized LSMO nanoparticles: in vitro evaluation of heat shock protein response.

Dextran stabilized La(0.7)Sr(0.3)MnO(3) (Dex-LSMO) is an alternative cancer hyperthermia agent holding considerable promise. Here, we have carried out a comparative study on radio frequency (~264 kHz) induced Dex-LSMO mediated heating and extraneous heating (mimicking generalized hyperthermia) in terms of changes in the morphology, proliferation pattern and induction of heat shock proteins in a human melanoma cell line (A375). Our results clearly show that the cellular effects seen with extraneous heating (60 min at 43 °C) could be reproduced by just six minutes of radio frequency induced Dex-LSMO mediated heating. More importantly, the observed enhanced levels of HSP 70 and 90 (molecular markers of heat shock that trigger favorable immunological reactions) seen with Dex-LSMO mediated heating were comparable to extraneous heating. These results suggest the possible utility of Dex-LSMO as a cancer hyperthermia agent.

Coal fly ash basins as an attractive nuisance to birds: parental provisioning exposes nestlings to harmful trace elements.

Birds attracted to nest around coal ash settling basins may expose their young to contaminants by provisioning them with contaminated food. Diet and tissues of Common Grackle (Quiscalus quiscala) nestlings were analyzed for trace elements to determine if nestlings were accumulating elements via dietary exposure and if feather growth limits elemental accumulation in other tissues. Arsenic, cadmium, and selenium concentrations in ash basin diets were 5× higher than reference diets. Arsenic, cadmium, and selenium concentrations were elevated in feather, liver, and carcass, but only liver Se concentrations approached levels of concern. Approximately 15% of the total body burden of Se, As, and Cd was sequestered in feathers of older (>5 days) nestlings, whereas only 1% of the total body burden of Sr was sequestered in feathers. Feather concentrations of only three elements (As, Se, and Sr) were correlated with liver concentrations, indicating their value as non-lethal indicators of exposure.

Preclinical assessment of gastrooesophageal tolerance of the new antiosteoporotic drug strontium ranelate: an endoscopic study in monkeys.

This study was aimed at evaluating the digestive tolerance of the new antiosteoporotic drug, strontium ranelate, and to compare it to that of another strontium salt, strontium chloride (SrCl2). Strontium ranelate, SrCl2, or placebo were administered orally (capsules) to 3 groups of 2 male and 2 female cynomolgus monkeys (Macaca fascicularis) once a day for 7 days at a dose of 2 g/day, which is the recommended therapeutic dose in man. Endoscopic examination of the oesophagus, the stomach and the first part of the duodenum was performed on fasted animals approximately 3 hr after the first (Day 1) and last dosing (Day 7), and, on Day 8 and Day 14 in case of lesions on Day 7. Strontium ranelate did not induce any acute or subchronic toxic effect on the gastric mucosa, the oesophagus and the first part of the duodenum. On the contrary, acute and superficial damages were noted on all animals receiving SrCl2 such as haemorrhagic and erosive lesions (formation of an ulcer in one male and a marked congestive antritis in one female). These effects were reversible after cessation of treatment. The microscopic examination of biopsies sampled at the site of gastric lesions revealed moderate granulocyte infiltration, indicating a local irritating origin of the lesions. Strontium ranelate by oral route is safe for the gastric mucosa while SrCl2 induced superficial and reversible lesions.

Elevated silver, barium and strontium in antlers, vegetation and soils sourced from CWD cluster areas: do Ag/Ba/Sr piezoelectric crystals represent the transmissible pathogenic agent in TSEs?

High levels of Silver (Ag), Barium (Ba) and Strontium (Sr) and low levels of copper (Cu) have been measured in the antlers, soils and pastures of the deer that are thriving in the chronic wasting disease (CWD) cluster zones in North America in relation to the areas where CWD and other transmissible spongiform encephalopathies (TSEs) have not been reported. The elevations of Ag, Ba and Sr were thought to originate from both natural geochemical and artificial pollutant sources--stemming from the common practise of aerial spraying with 'cloud seeding' Ag or Ba crystal nuclei for rain making in these drought prone areas of North America, the atmospheric spraying with Ba based aerosols for enhancing/refracting radar and radio signal communications as well as the spreading of waste Ba drilling mud from the local oil/gas well industry across pastureland. These metals have subsequently bioconcentrated up the foodchain and into the mammals who are dependent upon the local Cu deficient ecosystems. A dual eco-prerequisite theory is proposed on the aetiology of TSEs which is based upon an Ag, Ba, Sr or Mn replacement binding at the vacant Cu/Zn domains on the cellular prion protein (PrP)/sulphated proteoglycan molecules which impairs the capacities of the brain to protect itself against incoming shockbursts of sound and light energy. Ag/Ba/Sr chelation of free sulphur within the biosystem inhibits the viable synthesis of the sulphur dependent proteoglycans, which results in the overall collapse of the Cu mediated conduction of electric signals along the PrP-proteoglycan signalling pathways; ultimately disrupting GABA type inhibitory currents at the synapses/end plates of the auditory/circadian regulated circuitry, as well as disrupting proteoglycan co-regulation of the growth factor signalling systems which maintain the structural integrity of the nervous system. The resulting Ag, Ba, Sr or Mn based compounds seed piezoelectric crystals which incorporate PrP and ferritin into their structure. These ferrimagnetically ordered crystals multireplicate and choke up the PrP-proteoglycan conduits of electrical conduction throughout the CNS. The second stage of pathogenesis comes into play when the pressure energy from incoming shock bursts of low frequency acoustic waves from low fly jets, explosions, earthquakes, etc. (a key eco-characteristic of TSE cluster environments) are absorbed by the rogue 'piezoelectric' crystals, which duly convert the mechanical pressure energy into an electrical energy which accumulates in the crystal-PrP-ferritin aggregates (the fibrils) until a point of 'saturation polarization' is reached. Magnetic fields are generated on the crystal surface, which initiate chain reactions of deleterious free radical mediated spongiform neurodegeneration in surrounding tissues. Since Ag, Ba, Sr or Mn based piezoelectric crystals are heat resistant and carry a magnetic field inducing pathogenic capacity, it is proposed that these ferroelectric crystal pollutants represent the transmissible, pathogenic agents that initiate TSE.

An ultrastructural study of osteoclasts and chondroclasts in poorly calcified mandible induced by high doses of strontium diet to fetal mice.

A high dose strontium diet was fed to fetal mice from day 1 of gestation to birth in order to investigate the ultrastructural changes of osteoclasts/chondroclasts when associated with poorly calcified bone/cartilage. Calcification in the mandibular bone and condylar cartilage was extensively inhibited by this diet. Multinucleated osteoclasts and chondroclasts were observed on the mandibular alveolar bone and in the resorption area of the condylar cartilage, respectively. However, both cell types never formed ruffled borders and clear zones at the cell surfaces facing the matrices indicative of bone resorption, although they had well-developed organelles and vacuoles. Furthermore, they revealed signs of phagocytosis of the matrix vesicles. These results indicate that osteoclasts/chondroclasts can exhibit phagocytotic activity in response to requirements.

[Thermodynamic approach to the selection of polyuronide sequestrants for the protection of the human body from toxic metal ions. Interactions of polyuronides with strontium and calcium ions]. / Termodinamicheskii podkhod k vyboru poliuronidnykh kompleksoobrazovatelei dlia zashchity organizma cheloveka ot toksichnykh ionov metallov. Vzaimodeistvie poliuronidov s ionami strontsiia i kal'tsiia.

Selectivity of polyuronide sequestrants (pectate, alginates of various uronide composition) in respect to Sr2+ and Ca2+ ions has been evaluated in terms of thermodynamic affinity. It is suggested that there is no point in the use of pectate as a Sr(2+)-binding agent because at initial stages of reaction it reveals higher affinity to Ca2+ ions in comparison to Sr2+ ions. Contrary to pectate, alginates under similar conditions have higher affinity to Sr2+ ions. It is shown that these ions are bound only by blocks of L-guluronic acid residues in alginate macromolecules. The results obtained lend support to the advisability of the use of alginate preparations with the high content of L-guluronic acid residues for the excretion of Sr2+ ions from human body.

Strontium alters the complexed acidic phospholipid content of mineralizing tissues.

High dietary strontium induces rickets in both calcium-replete and calcium-deficient animals. To test the hypothesis that strontium directly perturbs complexed acidic phospholipid (CPLX) metabolism and thus, mineralization, the effect of strontium treatment on CPLX formation was studied in solution, in culture, and in growing rats. Synthetic CPLX containing calcium or strontium were found to be similar in composition. Strontium, however, appeared to incorporate into CPLX less avidly than calcium. Mineralizing chick limb bud mesenchymal cell cultures treated with strontium demonstrated a significantly increased CPLX content and decreased 45Ca uptake compared to calcium-treated cultures. Long bones from young growing rats fed a diet supplemented with strontium demonstrated defective mineralization based on radiologic and histologic analyses. Metaphyseal bone of strontium-fed rats contained significantly greater amounts of CPLX and had significantly lower ash weights compared with control bone. Thus, treatment of mineralizing tissues with strontium both in vitro and in vivo resulted in defective mineralization and an accumulation of CPLX. Strontium appears to perturb mineralization, in part, by a direct effect on the cells of mineralizing tissues.

[Toxic action of ergocalciferol in strontium rickets]. / Toksicheskoe deistvie érgokal'tsiferola pri strontsievom rakhite.

Tests conducted on albino rats of the Wistar line demonstrated that introduction of large doses of ergocalciferol (vitamin D2) to animals kept on a strontium-rich diet exhibiting signs of rickets brings about the development in them of specific manifestations of the D-vitamin activity, viz. rising level of calcium, strontium and inorganic phosphorus in the blood serum, lowering of the alkaline phosphatase activity and a greater degree of the soft tissues calcification.