IngredientsSelenodiglutathione is most commonly abbreviated SDG or GSSeSG, and is also rendered in the chemical literature as GS-Se-SG. The name reflects its structure: two molecules of the tripeptide glutathione (GSH) bridged by a single selenium atom in place of the sulfur-to-sulfur bond found in ordinary oxidized glutathione (GSSG). The compound is therefore a selenium-bridged glutathione conjugate, formally classified as a selenotrisulfide (a three-atom chalcogen bridge of the form âSâSeâSâ). The PubChem CID for the neutral molecule is 108069, with the molecular formula CââHââNâOââSâSe and the characteristic selenium isotopic pattern in mass spectra centered at m/z 693.1 for the [M+H]âș âžâ°Se ion.
Selenodiglutathione carries the molecular formula CââHââNâOââSâSe and is registered in PubChem under CID 108069. Its dianion form (CID 70679037) exists under physiological pH conditions. The compound is denoted GS-Se-SG in the research literature, and was formally identified by analytical methods in aqueous yeast extracts alongside the related mixed selenotrisulfide of glutathione and cysteinylglycine (GS-Se-SCG).
Selenium is an essential trace element for higher eukaryotes and is chemically closely related to sulfur. The capacity of selenium to substitute for sulfur in thiol-containing biomolecules underlies the formation of SDG. Selenium compounds like selenite (SeOâÂČâ») may form a covalent adduct with glutathione (GSH) in the form of selenodiglutathione (GS-Se-SG), which is assumed to be important in the metabolism of selenium.
SDG should be distinguished from the related but structurally distinct compound selenoglutathione (GSeH), in which the cysteine sulfur of a single glutathione molecule is replaced by selenium. Selenoglutathione (GSeH) is a water-soluble tripeptide in which the sulfur atom of biologically important reductant glutathione (GSH) is replaced by a selenium atom, and exhibits a higher reducing activity than GSH. GSSeSG is thus the selenium analogue of oxidized glutathione (GSSG), whereas GSeH is the selenium analogue of reduced glutathione (GSH).
SDG is not a conventional dietary ingredient in the way that selenomethionine or selenium-enriched yeast are. It is instead a metabolic intermediate that arises transiently in living cells whenever inorganic selenite encounters the intracellular glutathione pool. In reaction with reduced glutathione (GSH), inorganic selenium in the form of selenite forms a covalent adduct, selenodiglutathione (GS-Se-SG), which is further metabolized into selenide (HSeâ») by the thioredoxin or glutaredoxin systems.
In addition to its intracellular metabolic role, SDG has been identified as a natural constituent of selenium-enriched yeast. An approach for the identification of unknown selenium-containing biomolecules was developed, enabling the identification of selenodiglutathione (GS-Se-SG) and the mixed selenotrisulfide of glutathione and cysteinylglycine (GS-Se-SCG) in aqueous yeast extracts. The identification was achieved by two-dimensional liquid chromatography coupled with inductively coupled plasma mass spectrometry (ICPMS) and nanoelectrospray tandem mass spectrometry.
The transformation of selenite (SeOâÂČâ») with the participation of glutathione is slightly complicated because selenite (IV) reacts spontaneously with the reduced form of glutathione (GSH), resulting in the formation of selenodiglutathione (GS-Se-SG) and the oxidized form of glutathione (GSSG). This reaction has been confirmed both in isolated cell systems and in yeast metabolism studies. Recently, new selenium-containing glutathione species, including S-selenomethyl-glutathione and glutathione-S-selenoglutathione, have been identified in aqueous extracts of selenium-enriched yeast.
SDG itself is not commercially available as a direct dietary supplement in pure form. As a research tool and for biochemical studies, it is prepared synthetically by reacting stoichiometric amounts of reduced glutathione with sodium selenite under controlled conditions, or isolated from reaction mixtures. Selenium compounds like selenite may form a covalent adduct with glutathione (GSH) in the form of selenodiglutathione (GS-Se-SG); this has been studied by isolating GS-Se-SG and examining its reactions with NADPH and thioredoxin reductase from calf thymus or from Escherichia coli.
In the context of selenium supplementation, consumers most commonly encounter SDG indirectly, as a transient metabolite formed in the body from inorganic selenite. Naturally occurring selenium compounds like selenite and selenodiglutathione are metabolized to selenide in plants and animals. Selenium-enriched yeast preparations, which contain a complex mixture of selenium species including GS-Se-SG, represent the closest commercially available source.
Selenodiglutathione as an isolated or defined compound has no documented history of traditional use in any ethnobotanical, herbal, or cultural pharmacopoeia. Its chemical identity was only established in the latter decades of the twentieth century, and its biochemical role was characterised principally in the 1990s. The compound does not appear in the German Commission E monographs, ESCOP monographs, WHO herbal monographs, the United States Pharmacopeia, the European Pharmacopoeia, or any traditional medicine system.
The broader element selenium has no substantial pre-modern medical tradition either. Selenium was discovered as a chemical element in 1817, was recognized as an essential trace element only in the 1950sâ1970s, and its supplemental dietary use arose primarily in the context of twentieth-century nutritional science. Accordingly, any "traditional use" attributed to SDG would be a retroactive projection onto selenium-containing dietary sources (such as selenium-rich grains or animal proteins), not a historically documented practice involving SDG per se.
The formation of SDG from selenite and reduced glutathione is spontaneous, non-enzymatic, and occurs rapidly under physiological conditions. In the first step, GSH directly reacts to form diglutathione (GSSG) and unstable selenodiglutathione (GS-Se-SG); then selenodiglutathione further reacted with remaining GSH to form diglutathione and elemental selenium, Se(0). The reaction is governed by the redox potential of the glutathione couple and the reactivity of selenite toward thiol groups.
Glutathione and selenite spontaneously react to produce several selenium-containing compounds including selenodiglutathione, glutathioselenol, hydrogen selenide, and elemental selenium, as well as reactive oxygen species. This reaction sequence means that SDG is a transient but important node in the broader selenium metabolic pathway, particularly when the selenium source is selenite.
As a result of the reaction between selenite (IV) and GSH, selenodiglutathione (GS-Se-SG) and the oxidized form of glutathione (GSSG) are formed. The oxidized GSSG, a hazardous compound that forms disulfides with thiol-containing proteins, is transported to the vacuole or converted back into reduced GSH by glutathione reductase. In a further step, intracellular selenodiglutathione is converted into glutathionyselenol (GS-Se-H), and then to hydrogen selenide (HâSe/HSeâ»), with simultaneous formation of GSSG.
Naturally occurring selenium compounds like selenite and selenodiglutathione are metabolized to selenide in plants and animals. This highly reactive form of selenium can undergo methylation to form monomethylated and multimethylated species. These redox-active selenium metabolites are of particular biological and pharmacological interest since they are potent inducers of apoptosis in cancer cells.
The thioredoxin and glutaredoxin systems serve as the primary enzymatic drivers of SDG reduction. The mammalian thioredoxin and glutaredoxin systems efficiently reduce selenite and selenodiglutathione to selenide. The reactions are non-stoichiometric aerobically due to redox cycling of selenide with oxygen and thiols.
In yeast, SDG plays a dual role: it is a metabolic intermediate of selenite detoxification and a transport species for vacuolar selenium sequestration. Under high concentrations of selenium, yeasts store this element in cell vacuoles. The transport of selenium to the yeast cell interior is carried out using glutathione through a transporter belonging to the ABC family (protein Ycf1p) located in the vacuolar membrane. However, this mechanism, despite an efficient transfer of selenium in the form of selenodiglutathione (GS-Se-SG) into the vacuole, does not contribute to reduced toxicity.
Selenium present inside the yeast cell reacts with thiol groups of glutathione leading to the formation of selenodiglutathione and oxidization of glutathione; GS-Se-SG is then reduced via three pathways: (a) by GSH, (b) as a result of enzymatic processes by glutathione, and (c) thioredoxin reductase to GS-Se-H, and finally to hydrogen selenide.
In the liver, SDG serves as a principal vehicle for biliary elimination of selenium following selenite exposure. This study revealed that the biliary excretion of selenium depended on availability of hepatic GSH, probably for formation of GS-Se-SG, the putative cholephilic selenite metabolite. Biotransformation of selenite involves both reactions with GSH and methylations.
HPLC analysis of bile indicated absence of selenite and presence of selenodiglutathione (GS-Se-SG) and/or its hydrolysis products as the major biliary selenite metabolites. Depletion of hepatic glutathione decreased selenium excretion into bile by 60 and 80%, respectively, depending on the depleting agent. In contrast, inhibitors of methylation doubled the rate of biliary selenium excretion, indicating that methylation of downstream metabolites normally competes with biliary excretion of GS-Se-SG.
GSH is involved in the efflux of low-molecular-weight selenium compounds from cells, presumably via the formation of selenodiglutathione. Selenite inhibited the efflux of a fluorescent bimane-GS conjugate that is mediated by ATP-dependent multidrug-resistant proteins, implying the existence of an active transporter for selenodiglutathione.
The most thoroughly characterized biochemical action of SDG is its potent interaction with the mammalian thioredoxin system. The landmark study by Björnstedt, Kumar, and Holmgren (1992) published in the Journal of Biological Chemistry established this interaction definitively. Selenodiglutathione is a highly efficient oxidant of reduced thioredoxin and a substrate for mammalian thioredoxin reductase.
Isolated GS-Se-SG was studied in its reactions with NADPH and thioredoxin reductase from calf thymus or with thioredoxin reductase and thioredoxin from E. coli. Incubation of 0.1 ”M calf thymus thioredoxin reductase or 0.1 ”M thioredoxin reductase and 1 ”M thioredoxin from E. coli with 5, 10, or 20 ”M GS-Se-SG resulted in a fast initial reaction, followed by a large and continued oxidation of NADPH. Anaerobic incubation of calf thymus thioredoxin reductase and GS-Se-SG resulted only in oxidation of a stoichiometric amount of NADPH; admission of oxygen started continuous NADPH oxidation. This oxygen-dependent non-stoichiometric NADPH consumption is the hallmark of a redox-cycling mechanism generating reactive oxygen species (ROS).
Selenite and GS-Se-SG are efficient oxidants of thioredoxin (Trx) and inhibit the functions of the thioredoxin system. In addition, these selenium derivatives will also oxidize non-catalytic or structural cysteine residues which are characteristic of mammalian thioredoxins.
The ROS-generating capacity of SDG is central to its biological activities, whether cytotoxic or potentially chemopreventive. During the reduction of selenite by glutathione, the selenodiglutathione metabolite is formed. Through glutaredoxin and thioredoxin systems activity, selenodiglutathione is reduced to hydrogen selenide by glutathione. This pro-oxidant plays a central role in redox cycling with glutathione and producing superoxides and hydrogen peroxide, which further results in ROS generation.
The highly reactive selenide redox-cycles with oxygen and oxidizes NADPH, generating a massive non-stoichiometric reactive oxygen species (ROS) production. The downstream radical speciesâsuperoxide and hydrogen peroxideâmediate much of SDG's cellular toxicity, including DNA strand breaks and oxidative damage.
A distinct mechanism governs how SDG enters cells, which differs importantly from that of inorganic selenite. Cellular SDG uptake was decreased by pretreatment with specific inhibitors against gamma-glutamyl transpeptidase (GGT) or the cystine/glutamate antiporter (system xcâ»). Furthermore, siRNA against xCT, which is the light chain component of system xcâ», significantly decreased SDG incorporation. These data suggest an involvement of SDG in selenium incorporation, with SDG processed at the cell surface by GGT, leading to formation of selenodicysteine which, in turn, is likely to be imported via xCT.
Because GGT and xCT are highly expressed in cancer cells, these mechanisms mediated by the cystine transporter might underlie the cancer-selective toxicity of selenium. This differential expression pattern between cancer cells and normal cells is thought to be a key reason why SDG preferentially accumulates in, and is more toxic to, malignant cells.
SDG increases intracellular selenium accumulation and is more toxic than selenous acid (HâSeOâ), but the mechanisms for importing selenium compounds into cells are not fully understood.
An early line of biochemical research, dating to 1979, identified protein synthesis inhibition as a primary cellular action of SDG. GSSeSG inhibits the incorporation of [ÂłH]leucine into protein by 3T3-f cells. This inhibition cannot be reversed by removing GSSeSG and is correlated with the uptake of GSSeSG. Sodium selenite (NaâSeOâ) and oxidized glutathione had no inhibitory effect in this system. ÂłH-Uridine or ÂłH-thymidine incorporation into RNA or DNA was not inhibited, indicating that the primary action of GSSeSG was on protein synthesis. The irreversibility and specificity of this inhibitionâabsent for selenite and GSSG individuallyâpointed early on to SDG as having distinct intracellular targets.
A 1994 study from the Beatson Institute for Cancer Research provided pivotal evidence that SDG induces the tumor suppressor protein p53 and triggers apoptotic cell death. Selenodiglutathione (SDG), the initial metabolite of selenite, is shown to be a more powerful inhibitor of cell growth in vitro than selenite itself. This was established both with mouse erythroleukemia (MEL) cells and an ovarian cell line (A2780) known to contain wild-type p53.
Selenodiglutathione showed apoptotic effects in the low ”M concentration range towards different cancer cells including breast, ovarian, cervical, lymphoma, promyelocytic leukemia, and oral squamous cancer cells.
At nutritionally relevant (nanomolar) concentrations, SDG may serve as a selenium source supporting selenoprotein biosynthesis. Incubations with 100 nM sodium selenite, l- or dl-selenocystine, selenodiglutathione, or selenomethyl-selenocysteine increased selenoprotein P (SEPP) concentrations in culture medium up to 6.5-fold over control after 72 hours. This suggests that SDG, at low concentrations, can funnel selenium into the selenoprotein synthesis pathway rather than exerting cytotoxicityâa concentration-dependent duality that is characteristic of selenium biochemistry more broadly.
The most established physiological function of selenium is its presence in the detoxifying enzyme glutathione peroxidase as a selenocysteine residue in the active site. SDG, by contributing to the cellular selenide pool, participates in the upstream metabolism required for selenocysteine biosynthesis and incorporation into selenoproteins such as glutathione peroxidases and thioredoxin reductases.
Evidence strength: Preclinical only (cell-based and animal models); no direct human clinical evidence for SDG as an isolated compound.
The anticancer research on SDG is extensive at the preclinical level. Selenium is an essential antioxidative micronutrient but can exert cancer-selective cytotoxicity if the nutritional levels are too high. Selenodiglutathione (GSSeSG) is a primary selenium metabolite conjugated with two glutathione (GSH) moieties. GSSeSG has been suggested to be an important molecule for cytotoxicity. The proposed underlying mechanisms for the potent cytotoxicity of GSSeSG include: cellular intake; reductive metabolism; production of reactive oxygen species; oxidative damage to DNA; and apoptosis induction.
The 2015 study by Tobe et al. in the Journal of Biological Inorganic Chemistry examined GSSeSG cytotoxicity in MCF-7 human breast cancer cells. GSSeSG rather than selenite decreased cell viability and induced apoptosis accompanied by increases in intracellular selenium contents, such that GSSeSG-specific cytotoxicity may be ascribed to its preferable incorporation. Base oxidation and strand fragmentation in genomic DNA preceded cell death, suggesting that oxidative stress (including DNA damage) is crucial for GSSeSG cytotoxicity.
Selenite reacted with glutathione and produces hydrogen selenide via selenodiglutathione (SeDG), which induces cytotoxicity as cell apoptosis, ROS production, DNA damage, and adenosine-methionine methylation in the cellular nucleus.
SDG has also been positioned as an intermediate in broader selenium chemopreventive pathways. Numerous studies in animal models and more recent studies in humans have demonstrated cancer chemopreventive effects with selenium. There is extensive evidence that monomethylated forms of selenium are critical metabolites for chemopreventive effects. SDG, as an upstream metabolite on the pathway to monomethylated selenium species, may therefore contribute indirectly to these effects, though direct evidence is limited to cell culture and animal models.
Limitation: All mechanistic evidence for SDG-specific anticancer activity derives from in vitro cell culture studies. No controlled human clinical trials have tested SDG as an isolated intervention. The broader human evidence for selenium and cancer prevention, which involves the whole selenium metabolic network rather than SDG specifically, remains mixed and inconclusive in randomized controlled trials.
Evidence strength: Established biochemical mechanism (in vitro and cell-free systems); no human clinical data for SDG specifically.
The interaction of SDG with mammalian thioredoxin reductase is one of the best-characterized aspects of its biochemistry. Björnstedt M, Kumar S, Holmgren A demonstrated in a 1992 paper in the Journal of Biological Chemistry (267(12):8030â8034) that selenodiglutathione is a highly efficient oxidant of reduced thioredoxin and a substrate for mammalian thioredoxin reductase.
Selenite and GS-Se-SG are efficient oxidants of thioredoxin (Trx) and inhibit the functions of the thioredoxin system. In addition, these selenium derivatives also oxidize non-catalytic or structural cysteine residues characteristic of mammalian thioredoxins.
The thioredoxin system is recognized as a key regulator of cell growth, apoptosis, and the cellular redox environment. Thioredoxin (Trx) and thioredoxin reductase (TrxR) are redox-active proteins that participate in multiple cellular events, including growth promotion, apoptosis, and cytoprotection. SDG's capacity to efficiently oxidize and thereby inhibit this system at micromolar concentrations provides a mechanistic explanation for its growth-inhibitory and apoptosis-inducing effects.
Evidence strength: Strong biochemical and animal evidence; no dedicated human bioavailability studies for isolated SDG.
SDG occupies a pivotal position in the metabolic pathway through which inorganic selenium (primarily selenite) is assimilated in mammals. In reaction with reduced glutathione (GSH), inorganic selenium in the form of selenite forms a covalent adduct, selenodiglutathione (GS-Se-SG), which is further metabolized into selenide (HSeâ») by the thioredoxin or glutaredoxin systems.
Selenide may either transform to elemental selenium (Se°), or may undergo methylation, participate in biosynthesis and incorporation as selenocysteine in proteins, form selenosugars, and sequester metal ions. SDG thus serves as a key branch point from which selenium can be directed toward either excretion (as biliary GS-Se-SG) or utilization (via selenocysteine synthesis for selenoproteins).
Evidence strength: Established in animal models; emerging human observational evidence.
SDG and its downstream metabolite selenide participate in a well-characterized biochemical antagonism with arsenic, which has both toxicological and potential therapeutic significance. Glutathione and selenite spontaneously react to produce several selenium-containing compounds (selenodiglutathione, glutathioselenol, hydrogen selenide, and elemental selenium) as well as reactive oxygen species. Studies examined which compounds in the reaction pathway between glutathione and sodium selenite are responsible for toxicity; involvement of selenodiglutathione, elemental selenium, or reactive oxygen species in the thiol-assisted yeast toxicity could be ruled out.
The antagonism operates through the formation of a ternary selenium-arsenic-glutathione complex. Certain arsenic and selenium compounds show a remarkable mutual cancellation of toxicities, where a lethal dose of one can be voided by an equimolar and otherwise lethal dose of the other. The molecular basis of this antagonism is the formation and biliary excretion of seleno-bis-(S-glutathionyl) arsinium anion [(GS)âAsSe]â».
Evidence strength: Cell-line and biochemical evidence; no dedicated human studies.
Beyond its role in selenium uptake, SDG participates in cellular selenium efflux. Although previous studies have suggested the involvement of glutathione and/or thioredoxin reductase in selenite metabolism, intracellular selenite metabolism remains largely unknown. GSH depletion did not affect the amount of selenoprotein in Hepa 1â6 cells, suggesting that GSH does not play a central role in the reduction of selenite in selenoprotein biosynthesis. On the other hand, GSH is involved in the efflux of low-molecular-weight selenium compounds from cells, presumably via the formation of selenodiglutathione.
This efflux function implies that SDG contributes to selenium homeostasis not just by metabolizing selenite within cells but also by facilitating the secretion of selenium species, a process relevant to understanding selenium distribution across tissues.
SDG is deeply embedded in the cellular redox network. The thioredoxin and glutaredoxin systems are essential to preserve the intracellular redox balance via reduction of protein disulfides and glutathione mixed disulfides. SDG, by engaging both systems as a substrate, influences the overall redox state of the cell. At high concentrations, this engagement is destructive (through ROS generation); at lower, more physiological concentrations, it may support the controlled turnover of these systems.
The most extensively studied health-relevant context for SDG is cancer cell biology. The proposed underlying mechanisms for the potent cytotoxicity of GSSeSG include: cellular intake; reductive metabolism; production of reactive oxygen species; oxidative damage to DNA; and apoptosis induction. The cancer-selectivity of SDG's cytotoxicity has been attributed partly to differential expression of its cellular uptake machinery (GGT and xCT) in malignant versus normal cells.
Selenium is an essential trace element and is regarded as a protective agent against cancer. In particular, antioxidant effects of selenoenzymes contribute to cancer prevention. Selenium can also produce reactive oxygen species and, thereby, exert cancer-selective cytotoxicity.
As a precursor to selenide and subsequently to selenoprotein biosynthesis, SDG participates indirectly in immune regulation. Selenoproteins act as antioxidant warriors for thyroid regulation, male-fertility enhancement, and anti-inflammatory actions. They also participate indirectly in the mechanism of wound healing as oxidative stress reducers. Glutathione peroxidase (GPX) is the major selenoprotein present in the human body, which assists in the control of excessive production of free radicals at the site of inflammation. To the extent that SDG contributes to the supply pool for selenoprotein synthesis, it may support these functions, but no studies have examined this relationship directly in human subjects.
The liver is the primary site of SDG formation and biliary handling. The biliary excretion of selenium depended on availability of hepatic GSH, probably for formation of GS-Se-SG, the putative cholephilic selenite metabolite. Hepatic glutathione status is therefore a key determinant of how efficiently inorganic selenium is excreted versus retained and further metabolized.
Research on selenium- and glutathione-enriched yeast provides some indirect context. Enriched yeast with the highest selenium and glutathione levels reduced weight loss induced by diabetes, inhibited increases in plasma cholesterol and triglycerides caused by a high-cholesterol and high-fat diet, increased the time taken for oxidation of lower density lipoproteins (lag time), and inhibited the formation of atherosclerosis better than low selenium/glutathione yeast supplementation. These effects were attributed to the combined antioxidant actions of the selenium-glutathione complex, though this study used a hamster model and did not test SDG as an isolated compound. Evidence is preliminary and animal-model based.
Because SDG has not been developed as a standardized human dietary supplement, there are no established human clinical dosages. The concentrations employed across published research are summarized below, drawn exclusively from stated experimental conditions in the primary literature:
No human pharmacokinetic data or dose-response studies for orally administered SDG are available in the peer-reviewed literature retrieved. The compound is not listed in official dietary reference intakes (DRIs) for selenium, which are instead expressed in terms of total selenium intake from all dietary sources.
SDG occupies a dual position in selenium biochemistry: at physiological concentrations, it serves as a metabolic intermediate required for selenoprotein synthesis and cellular selenium homeostasis; at supraphysiological concentrations, it is a potent cytotoxin. Selenium is an essential antioxidative micronutrient but can exert cancer-selective cytotoxicity if the nutritional levels are too high.
Selenodiglutathione, an intermediate in the formation of superoxide from selenite and glutathione, has been found to be even more toxic than selenite itself. This heightened toxicity relative to its precursor (selenite) is important: it means that conditions that accelerate SDG formationâsuch as high selenium intake combined with a replete glutathione poolâcould generate a more reactive and cytotoxic selenium species than selenite alone.
The formation and fate of SDG are tightly coupled to intracellular glutathione (GSH) availability. HPLC analysis showed that selenodiglutathione and/or its hydrolysis products are the major biliary selenite metabolites, and depletion of hepatic glutathione decreased selenium excretion into bile by 60â80%. Consequently, conditions that deplete GSH (disease states, chemotherapy, nutritional deficiency) may alter SDG metabolism and selenium homeostasis in clinically relevant ways.
Conversely, conditions that markedly elevate GSH (as in cancer cells, which often overexpress GSH biosynthetic enzymes) may increase SDG formation from selenite, potentially amplifying both selenium cytotoxicity and cellular selenium accumulation.
By acting as a potent oxidant and substrate for thioredoxin reductase, SDG can impair the function of the thioredoxin system at high concentrations. Selenite and GS-Se-SG are efficient oxidants of thioredoxin (Trx) and inhibit the functions of the thioredoxin system. The thioredoxin system is indispensable for maintaining cellular redox homeostasis, DNA synthesis (via ribonucleotide reductase), and the regulation of transcription factors including NF-ÎșB and AP-1. Disruption of this system has broad consequences for cell survival, which underlies both the cytotoxic and potential anticancer properties of SDG.
SDG's downstream metabolite, selenide, reacts with arsenic compounds to form the biliary co-excretion product [(GS)âAsSe]â». Certain arsenic and selenium compounds show a remarkable mutual cancellation of toxicities, where a lethal dose of one can be voided by an equimolar and otherwise lethal dose of the other. This interaction has been confirmed in animal models and represents a case where selenium metabolism via the SDG/selenide pathway is directly relevant to the safety profile of co-exposure to arsenic.
The highly reactive selenide generated from SDG redox-cycles with oxygen and oxidizes NADPH, generating a massive non-stoichiometric reactive oxygen species (ROS) production. At high concentrations or in cells with limited antioxidant capacity, this ROS burden can damage DNA, lipids, and proteins. Selenite and other selenium compounds have strong inhibitory or, at low concentrations, stimulatory effects on the growth of normal as well as tumor cells by yet incompletely characterized mechanisms.
Trial evidence has suggested that supplementing those who already have adequate selenium intake and maximal selenoprotein activity/concentration with additional selenium may increase the risk of alopecia, dermatitis, and type-2 diabetes, reminding us that selenium was first known as a toxic element. These findings, while attributable to total selenium intake rather than SDG specifically, are relevant because SDG is a metabolic intermediate formed from supplemental inorganic selenium (selenite), and its formation and intracellular actions are concentration-dependent.
Health conditions that Selenodiglutathione may help support.
Body systems that Selenodiglutathione may help support.
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