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Selenium (Se) compounds have demonstrated anticancer properties in both preclinical and clinical studies, with particular promise in combination therapy where the optimal form and dose of selenium has yet to be established. In a phase I randomised double-blinded study, the safety, tolerability and pharmacokinetic (PK) profiles of sodium selenite (SS), Se-methylselenocysteine (MSC) and seleno-l-methionine (SLM) were compared in patients with chronic lymphocytic leukaemia and a cohort of patients with solid malignancies. Twenty-four patients received 400 μg of elemental Se as either SS, MSC or SLM for 8 weeks. None of the Se compounds were associated with any significant toxicities, and the total plasma Se AUC of SLM was markedly raised in comparison to MSC and SS. DNA damage assessment revealed negligible genotoxicity, and some minor reductions in lymphocyte counts were observed. At the dose level used, all three Se compounds are well-tolerated and non-genotoxic. Further analyses of the pharmacodynamic effects of Se on healthy and malignant peripheral blood mononuclear cells will inform the future evaluation of higher doses of these Se compounds. The study is registered under the Australian and New Zealand Clinical Trials Registry No: ACTRN12613000118707.

Quantum dots have been used in biomedical research for imaging 1 , 2 , diagnostics 3 , 4 and sensing purposes 5 , 6 . However, concerns over the cytotoxicity of their heavy metal constituents 7 , 8 and conflicting results from in vitro 7 , 9 and small animal 10 , 11 , 12 , 13 , 14 toxicity studies have limited their translation towards clinical applications. Here, we show in a pilot study that rhesus macaques injected with phospholipid micelle-encapsulated CdSe/CdS/ZnS quantum dots do not exhibit evidence of toxicity. Blood and biochemical markers remained within normal ranges following treatment, and histology of major organs after 90 days showed no abnormalities. Our results show that acute toxicity of these quantum dots in vivo can be minimal. However, chemical analysis revealed that most of the initial dose of cadmium remained in the liver, spleen and kidneys after 90 days. This means that the breakdown and clearance of quantum dots is quite slow, suggesting that longer-term studies will be required to determine the ultimate fate of these heavy metals and the impact of their persistence in primates. Six rhesus macaques injected with a cadmium-based quantum-dot formulation survived without any evidence of toxicity, but cadmium remained in certain organs after 90 days.

[...]the European Food Safety Authority established a TUIL of 60 and 90 μg/d, for 1 to 3 and 3 to 6 y olds, respectively, reflecting the poorer selenium status of European soils [11]. Because chemical content of biological samples correlate poorly with degree of toxicity [12] a more physiological approach assesses the amount of selenium necessary to optimize function of the glutathione peroxidise (GPx) selenoenzymes that regulate cellular redox processes by catalyzing the reduction of organic hydroperoxides [13].

Detailed safety assessment of sodium selenite and bioselenium (bio-Se) was conducted and the results were compared and discussed for the purpose of assessing safety of bio-Se for use in food applications. In this work, acute toxicity studies, micronucleus test, and sperm aberration study in mice, 30-day feeding test of mice, were conducted to evaluate the toxicity of bio-Se obtained from yeast with different fermentation time (transformative time: one month, three months, and six months), and the results were compared with that of inorganic Se (sodium selenite). LD50 of sodium selenite was calculated to be 21.17 mg/kg. LD50 of bio-Se obtained from yeast with different fermentation time was calculated to be 740.2 mg/kg, 915.3 mg/kg, and 1179.0 mg/kg, respectively. In the genotoxicity test, bio-Se did not show cytotoxicity and genotoxicity of mice while sodium selenite at all dose groups was significantly different from the negative group. In the 30-day subchronic oral toxicity study, sodium selenite may slow down the growth of the mice and lead to organic damage to some extent. Bio-Se had facilitated effect towards the body weight of the mice and had no significant effect on the shape and function of the important organs of the mice.

Quantum dots that contain cadmium, selenium and zinc are not toxic to monkeys for periods of up to 90 days, but longer-term studies are needed to determine the ultimate fate of the heavy metals that accumulate in the organs.

The cluster Re6Se8I63− has been shown to induce preferential cell death of a hepatic carcinoma cell line, thus becoming a promising anti-cancer drug. Whether this cluster induces acute hemolysis or if it interacts with albumin remains unclear. The effect of acute exposure of human red blood cells to different concentrations of the cluster with and without albumin is described. Red blood cells from healthy donors were isolated, diluted at 1% hematocrit and exposed to the cluster (25–150 µM) at 37 °C, under agitation. Hemolysis and morphology were analyzed at 1 and 24 h. The potential protection of 0.1% albumin was also evaluated. Exposition to therapeutic doses of the cluster did not induce acute hemolysis. Similar results were observed following 24 h of exposition, and albumin slightly reduced hemolysis levels. Furthermore, the cluster induced alteration in the morphology of red blood cells, and this was prevented by albumin. Together, these results indicate that the cluster Re6Se8I63− is not a hemolytic component and induces moderate morphological alterations of red blood cells at high doses, which are prevented by co-incubation with albumin. In conclusion, the cluster Re6Se8I63− could be intravenously administered in animals at therapeutic doses for in vivo studies.

Selenium is one of the elements classified within the group of micronutrients which are necessary in trace amounts for the proper functioning of organisms. Selenium participates in the protection of cells against excess H2O2, in heavy metal detoxification, and regulation of the immune and reproductive systems as well. It also ensures the proper functioning of the thyroid gland. Selenium induces the occurrence of the selenoprotein synthesis process involved in the antioxidant defense mechanism of the organism. Recent years have brought much success in the studies on selenium. Anticarcinogenic properties of selenium against some cancers have been reported. Supplementation is increasingly becoming a solution to this problem. A large number of different supplementation methods are promoting studies in this area. Slight differences in the selenium content can result in excess or deficiency, therefore supplementation has to be done carefully and cautiously.

Selenium is generally known as an antioxidant due to its presence in selenoproteins as selenocysteine, but it is also toxic. The toxic effects of selenium are, however, strictly concentration and chemical species dependent. One class of selenium compounds is a potent inhibitor of cell growth with remarkable tumor specificity. These redox active compounds are pro-oxidative and highly cytotoxic to tumor cells and are promising candidates to be used in chemotherapy against cancer. Herein we elaborate upon the major forms of dietary selenium compounds, their metabolic pathways, and their antioxidant and pro-oxidant potentials with emphasis on cytotoxic mechanisms. Relative cytotoxicity of inorganic selenite and organic selenocystine compounds to different cancer cells are presented as evidence to our perspective. Furthermore, new novel classes of selenium compounds specifically designed to target tumor cells are presented and the potential of selenium in modern oncology is extensively discussed.

Morphogenesis of the clearnose skate, Raja eglanteria, was not significantly inhibited as a result of 7 days of exposure to 1-2 mM selenate in the sea water during Days 59-69 of embryonic development (hatching would normally have occurred at 82 +/- 4 days of incubation). Although corneal transparency appeared normal in the eye, preliminary measurements of the thickness of Bowman's layer of the cornea suggested that it was significantly thinner in the corneas of embryos exposed to 1-2 mM selenate. Selenate is an ion reported to inhibit sulfation of glycosaminoglycans in connective tissue.

This study attempted to address molecular, developmental, and physiological responses of tomato plants to foliar applications of selenium nanoparticles (nSe) at 0, 3, and 10 mgl -1 or corresponding doses of sodium selenate (BSe). The BSe/nSe treatment at 3 mgl -1 increased shoot and root biomass, while at 10 mgl -1 moderately reduced biomass accumulation. Foliar application of BSe/nSe, especially the latter, at the lower dose enhanced fruit production, and postharvest longevity, while at the higher dose induced moderate toxicity and restricted fruit production. In leaves, the BSe/nSe treatments transcriptionally upregulated miR172 (mean = 3.5-folds). The Se treatments stimulated the expression of the bZIP transcription factor (mean = 9.7-folds). Carotene isomerase ( CRTISO ) gene was transcriptionally induced in both leaves and fruits of the nSe-treated seedlings by an average of 5.5 folds. Both BSe or nSe at the higher concentration increased proline concentrations, H 2 O 2 accumulation, and lipid peroxidation levels, suggesting oxidative stress and impaired membrane integrity. Both BSe or nSe treatments also led to the induction of enzymatic antioxidants (catalase and peroxidase), an increase in concentrations of ascorbate, non-protein thiols, and soluble phenols, as well as a rise in the activity of phenylalanine ammonia-lyase enzyme. Supplementation at 3 mgl -1 improved the concentration of mineral nutrients (Mg, Fe, and Zn) in fruits. The bioaccumulated Se contents in the nSe-treated plants were much higher than the corresponding concentration of selenate, implying a higher efficacy of the nanoform towards biofortification programs. Se at 10 mgl -1 , especially in selenate form, reduced both size and density of pollen grains, indicating its potential toxicity at the higher doses. This study provides novel molecular and physiological insights into the nSe efficacy for improving plant productivity, fruit quality, and fruit post-harvest longevity.