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Here, we addressed the pharmacology and toxicology of synthetic organoselenium compounds and some naturally occurring organoselenium amino acids. The use of selenium as a tool in organic synthesis and as a pharmacological agent goes back to the middle of the nineteenth and the beginning of the twentieth centuries. The rediscovery of ebselen and its investigation in clinical trials have motivated the search for new organoselenium molecules with pharmacological properties. Although ebselen and diselenides have some overlapping pharmacological properties, their molecular targets are not identical. However, they have similar anti-inflammatory and antioxidant activities, possibly, via activation of transcription factors, regulating the expression of antioxidant genes. In short, our knowledge about the pharmacological properties of simple organoselenium compounds is still elusive. However, contrary to our early expectations that they could imitate selenoproteins, organoselenium compounds seem to have non-specific modulatory activation of antioxidant pathways and specific inhibitory effects in some thiol-containing proteins. The thiol-oxidizing properties of organoselenium compounds are considered the molecular basis of their chronic toxicity; however, the acute use of organoselenium compounds as inhibitors of specific thiol-containing enzymes can be of therapeutic significance. In summary, the outcomes of the clinical trials of ebselen as a mimetic of lithium or as an inhibitor of SARS-CoV-2 proteases will be important to the field of organoselenium synthesis. The development of computational techniques that could predict rational modifications in the structure of organoselenium compounds to increase their specificity is required to construct a library of thiol-modifying agents with selectivity toward specific target proteins.

The advance in the area of synthesis and reactivity of organoselenium, as well as the discovery that selenium was the cause of severe intoxication episodes of livestock in the 1930s and the subsequent determination that selenium was an essential trace element in the diet for mammals, has motivated intense studies of the biological properties of both organic and inorganic selenium compounds. In this review, we shall cover a wide range of toxicological and pharmacological effects, in which organoselenium compounds are involved but the effects of inorganic compounds were not discussed in detail here. The molecular toxicity of inorganic selenium was described in relation to its interaction with endogenous –SH groups to allow a comparison with that of synthetic organoselenium compounds. Furthermore, in view of the recent points of epidemiological evidence that overexposure to selenium can facilitate the appearance of chronic degenerative diseases, we also briefly revised the history of selenium toxicity and physiology and how environmental selenium can reach inside the mammalian cells. The biological narrative of the element selenium, in the last century, has been marked by a contrast between its toxic and its beneficial effects. Thus, the potential therapeutic use of simple organoselenium compounds has not yet been sufficiently explored and, consequently, we cannot discard this class of compounds as promising pharmaceutical agents. In effect, the future of the organochalcogens as pharmacological agents will depend on more detailed toxicological studies in the oncoming years.

Ebselen, an organoselenium compound, mimics glutathione peroxidase activity. It is a multifunctional compound, which catalyzes several essential reactions for the protection of cellular components from oxidative and free radical damage. Based on a number of in vitro and in vivo studies, various mechanisms are proposed to understand the biomedical actions of ebselen in health and diseases. It modulates metallo-proteins, enzymatic cofactors, gene expression, epigenetics, antioxidant defenses and immune systems. Owing to these properties, ebselen is currently under clinical trials for the prevention and treatment of various disorders such as cardiovascular diseases, arthritis, stroke, atherosclerosis, and cancer. A few ebselen-based pharmaceutical agents are under extensive investigation. As ebselen has been shown to have significant cellular toxicity, appropriate studies are needed to redesign the ebselen-based therapy for clinical trials. This review summarizes current understanding of the biochemical and molecular properties, and pharmacological applications of ebselen and future directions in this area of research.

Studies of recent decades have repeatedly demonstrated the cytotoxic effect of selenium-containing compounds on cancer cells of various origins. Particular attention in these studies is paid to methylseleninic acid, a widespread selenium-containing compound of organic nature, for several reasons: it has a selective cytotoxic effect on cancer cells, it is cytotoxic in small doses, it is able to generate methylselenol, excluding the action of the enzyme β-lyase. All these qualities make methylseleninic acid an attractive substrate for the production of anticancer drugs on its basis with a well-pronounced selective effect. However, the studies available to date indicate that there is no strictly specific molecular mechanism of its cytotoxic effect in relation to different cancer cell lines and cancer models. This review contains generalized information on the dose- and time-dependent regulation of the toxic effect of methylseleninic acid on the proliferative properties of a number of cancer cell lines. In addition, special attention in this review is paid to the influence of this selenium-containing compound on the regulation of endoplasmic reticulum stress and on the expression of seven selenoproteins, which are localized in the endoplasmic reticulum.

This paper presents a new method for the simultaneous speciation analysis of arsenic (As(III)-arsenite, As(V)-arsenate, DMA-dimethylarsinic acid, MMA-methylarsonic acid, and AsB-arsenobetaine) and selenium (Se(IV)-selenite, Se(VI)-selenate, Se-Methionine, and Se-Cystine), which was applied to a variety of seafood and onion samples. The determination of the forms of arsenic and selenium was undertaken using the High-Performance Liquid Chromatography Inductively Coupled Plasma Mass Spectrometry (HPLC–ICP–MS) analytical technique. The separation of both organic and inorganic forms of arsenic and selenium was performed using two analytical columns: an anion exchange column, Dionex IonPac AS22, containing an alkanol quaternary ammonium ion, and a double bed cation–anion exchange guard column, Dionex Ion Pac CG5A, containing, as a first layer, fully sulfonated latex for cation exchange and a fully aminated layer for anion exchange as the second layer. The ammonium nitrate, at pH = 9.0, was used as a mobile phase. The method presented here allowed us to separate the As and Se species within 10 min with a suitable resolution. The applicability was presented with different sample matrix types: seafood and onion.

Without a doubt, our current antimicrobials are losing the battle in the fight against newly-emerged multidrug-resistant pathogens. There is a pressing, unmet need for novel antimicrobials and novel approaches to develop them; however, it is becoming increasingly difficult and costly to develop new antimicrobials. One strategy to reduce the time and cost associated with antimicrobial innovation is drug repurposing, which is to find new applications outside the scope of the original medical indication of the drug. Ebselen, an organoselenium clinical molecule, possesses potent antimicrobial activity against clinical multidrug-resistant Gram-positive pathogens, including Staphylococcus, Streptococcus, and Enterococcus, but not against Gram-negative pathogens. Moreover, the activity of ebselen against Gram-positive pathogens exceeded those activities determined for vancomycin and linezolid, drugs of choice for treatment of Enterococcus and Staphylococcus infections. The minimum inhibitory concentrations of ebselen at which 90% of clinical isolates of Enterococcus and Staphylococcus were inhibited (MIC90) were found to be 0.5 and 0.25 mg/L, respectively. Ebselen showed significant clearance of intracellular methicillin-resistant S. aureus (MRSA) in comparison to vancomycin and linezolid. We demonstrated that ebselen inhibits the bacterial translation process without affecting mitochondrial biogenesis. Additionally, ebselen was found to exhibit excellent activity in vivo in a Caenorhabditis elegans MRSA-infected whole animal model. Finally, ebselen showed synergistic activities with conventional antimicrobials against MRSA. Taken together, our results demonstrate that ebselen, with its potent antimicrobial activity and safety profiles, can be potentially used to treat multidrug resistant Gram-positive bacterial infections alone or in combination with other antibiotics and should be further clinically evaluated.

To investigate whether selenium (Se) accumulation in plants provides a chemical defense against generalist insect herbivores, the feeding preference and performance of a mix of orthopteran species were investigated. The selenium hyperaccumulator Stanleya pinnata and accumulator Brassica juncea were used in herbivory studies in the laboratory, and S. pinnata was also used in a manipulative field experiment. In laboratory studies, both crickets and grasshoppers avoided plants pretreated with selenate, while those given no choice died after eating leaves with elevated Se (447 ± 68 and 230 ± 68 μg Se g⁻¹ DW, respectively). B. juncea has previously been shown to accumulate selenate, while S. pinnata hyperaccumulates methyl-selenocysteine. Thus, these findings demonstrate that both inorganic and organic forms of selenium protect plants from herbivory. Grasshoppers fed S. pinnata contained methylselenocysteine in their midgut and absorbed this form into surrounding tissues. In a manipulative field experiment, methylselenocysteine protected S. pinnata from invertebrate herbivory and increased its long-term survival rate over an entire growth season. In native habitats of selenium hyperaccumulators, orthopterans represent a major group of insect herbivores. Protection offered by organic selenium accumulation against these herbivores may have promoted the evolution of selenium hyperaccumulation in plants.

Variously synthesized and fabricated Bi 2 Se 3 nanoparticles (NPs) have recently been explored for their theranostic properties. Herein, we investigated the long term in-vivo biodistribution of Bi 2 Se 3 NPs and systematically screened its immune-toxic potential over lungs and other secondary organs post intratracheal instillation. X-Ray CT scan and ICP MS results revealed significant particle localization and retention in lungs monitored for 1 h and 6 months time period respectively. Subsequent particle trafficking was observed in liver, the major reticuloendothelial organ followed by gradual but incomplete renal clearance. Pulmonary cytotoxicity was also found to be associated with persistent neutrophilic and ROS generation at all time points following NP exposure. The inflammatory markers along with ROS generation further promoted oxidative stress and exaggerated additional inflammatory pathways leading to cell death. The present study, therefore, raises serious concern about the hazardous effects of Bi 2 Se 3 NPs and calls for further toxicity assessments through different administration routes and doses as well.

Background: Selenium is an essential trace element that also elicits toxic effects at modest intakes. Investigations of selenium metabolites in urine can help our understanding of the transformations taking place in the body that produce these beneficial and detrimental effects. There is, however, considerable discord in the scientific literature regarding the selenium metabolites thought to play important roles in these biotransformation processes. Approach: We critically assessed the published reports on selenium urinary metabolites, from the first report in 1969 to the present, in terms of the rigor of the data on which structures have been proposed. Content: We present and discuss data from ∼60 publications reporting a total of 16 identified selenium metabolites in urine of humans or rats, a good model for human selenium metabolism. We assessed the analytical methods used and the validity of the ensuing structural assignments. Summary: Many of the studies of selenium metabolites in urine appear to have assigned incorrect structures to the compounds. The long-held view that trimethylselenonium ion is a major human urinary metabolite appears unjustified. On the other hand, recent work describing selenosugars as major urinary metabolites looks sound and provides a firm basis for future studies.

This study investigates the efficacy of diphenyl diselenide [(PhSe)2] in attenuating methylmercury- (MeHg-)induced toxicity in rats. Adult rats were treated with MeHg [5 mg/kg/day, intragastrically (i.g.)] and/ or (PhSe)2 [1 mg/kg/day, intraperitoneally (i.p.)] for 21 days. Body weight gain and motor deficits were evaluated prior to treatment, on treatment days 11 and 21. In addition, hepatic and cerebral mitochondrial function (reactive oxygen species (ROS) formation, total and nonprotein thiol levels, membrane potential (ΔΨm), metabolic function, and swelling), hepatic, cerebral, and muscular mercury levels, and hepatic, cerebral, and renal thioredoxin reductase (TrxR) activity were evaluated. MeHg caused hepatic and cerebral mitochondrial dysfunction and inhibited TrxR activity in liver (38,9%), brain (64,3%), and kidney (73,8%). Cotreatment with (PhSe)2 protected hepatic and cerebral mitochondrial thiols from depletion by MeHg but failed to completely reverse MeHg’s effect on hepatic and cerebral mitochondrial dysfunction or hepatic, cerebral, and renal inhibition of TrxR activity. Additionally, the cotreatment with (PhSe)2 increased Hg accumulation in the liver (50,5%) and brain (49,4%) and increased the MeHg-induced motor deficits and body-weight loss. In conclusion, these results indicate that (PhSe)2 can increase Hg body burden as well as the neurotoxic effects induced by MeHg exposure in rats.