Immunomodulatory and Anti-Inflammatory Properties of Selenium-Containing Agents: Their Role in the Regulation of Defense Mechanisms against COVID-19.

The review presents the latest data on the role of selenium-containing agents in the regulation of diseases of the immune system. We mainly considered the contributions of selenium-containing compounds such as sodium selenite, methylseleninic acid, selenomethionine, and methylselenocysteine, as well as selenoproteins and selenium nanoparticles in the regulation of defense mechanisms against various viral infections, including coronavirus infection (COVID-19). A complete description of the available data for each of the above selenium compounds and the mechanisms underlying the regulation of immune processes with the active participation of these selenium agents, as well as their therapeutic and pharmacological potential, is presented. The main purpose of this review is to systematize the available information, supplemented by data obtained in our laboratory, on the important role of selenium compounds in all of these processes. In addition, the presented information makes it possible to understand the key differences in the mechanisms of action of these compounds, depending on their chemical and physical properties, which is important for obtaining a holistic picture and prospects for creating drugs based on them.

Selenium Kinetics in Humans Change Following 2 Years of Supplementation With Selenomethionine.

Background: Selenium (Se) is a nutritionally essential trace element and health may be improved by increased Se intake. Previous kinetic studies have shown differences in metabolism of organic vs. inorganic forms of Se [e.g., higher absorption of selenomethionine (SeMet) than selenite (Sel), and more recycling of Se from SeMet than Sel]. However, the effects on Se metabolism after prolonged Se supplementation are not known. Objective: To determine how the metabolism and transport of Se changes in the whole-body in response to Se-supplementation by measuring Se kinetics before and after 2 years of Se supplementation with SeMet. Methods: We compared Se kinetics in humans [n = 31, aged 40 ± 3 y (mean ± SEM)] studied twice after oral tracer administration; initially (PK1), then after supplementation for 2 y with 200 µg/d of Se as selenomethionine (SeMet) (PK2). On each occasion, we administered two stable isotope tracers of Se orally: SeMet, the predominant food form, and selenite (Na276SeO3, or Sel), an inorganic form. Plasma and RBC were sampled for 4 mo; urine and feces were collected for the initial 12 d of each period. Samples were analyzed for tracers and total Se by isotope dilution GC-MS. Data were analyzed using a compartmental model, we published previously, to estimate fractional transfer between pools and pool masses in PK2. Results: We report that fractional absorption of SeMet or Sel do not change with SeMet supplementation and the amount of Se absorbed increased. The amount of Se excreted in urine increases but does not account for all the Se absorbed. As a result, there is a net incorporation of SeMet into various body pools. Nine of the 11 plasma pools doubled in PK2; two did not change. Differences in metabolism were observed for SeMet and Sel; RBC uptake increased 247% for SeMet, urinary excretion increased from two plasma pools for Sel and from two different pools for SeMet, and recycling to liver/tissues increased from one plasma pool for Sel and from two others for SeMet. One plasma pool increased more in males than females in PK2. Conclusions: Of 11 Se pools identified kinetically in human plasma, two did not increase in size after SeMet supplementation. These pools may be regulated and important during low Se intake.

A general covalent binding model between cytotoxic selenocompounds and albumin revealed by mass spectrometry and X-ray absorption spectroscopy.

Selenocompounds (SeCs) are promising therapeutic agents for a wide range of diseases including cancer. The treatment results are heterogeneous and dependent on both the chemical species and the concentration of SeCs. Moreover, the mechanisms of action are poorly revealed, which most probably is due to the detection methods where the quantification is based on the total selenium as an element. To understand the mechanisms underlying the heterogeneous cytotoxicity of SeCs and to determine their pharmacokinetics, we investigated selenium speciation of six SeCs representing different categories using liquid chromatography-mass spectrometry (LC-MS) and X-ray absorption spectroscopy (XAS) and the cytotoxicity using leukemic cells. SeCs cytotoxicity was correlated with albumin binding degree as revealed by LC-MS and XAS. Further analysis corroborated the covalent binding between selenol intermediates of SeCs and albumin thiols. On basis of the Se-S model, pharmacokinetic properties of four SeCs were for the first time profiled. In summary, we have shown that cytotoxic SeCs could spontaneously transform into selenol intermediates that immediately react with albumin thiols through Se-S bond. The heterogeneous albumin binding degree may predict the variability in cytotoxicity. The present knowledge will also guide further kinetic and mechanistic investigations in both experimental and clinical settings.

Feed-to-Fillet Transfer of Selenite and Selenomethionine Additives to Plant-Based Feeds to Farmed Atlantic Salmon Fillet.

This study investigated the transfer kinetics of dietary selenite and selenomethionine (SeMet) to the fillet of farmed Atlantic salmon (Salmo salar). The uptake and elimination rate constants of the two selenium (Se) forms were determined in Atlantic salmon fed either selenite- or SeMet-supplemented diets followed by a depuration period. The fillet half-life of selenite and SeMet was 779 ± 188 and 339 ± 103 days, respectively. The elimination and uptake rates were used in a simple one-compartmental kinetic model to predict levels in fillet based on long-term (whole production cycle) feeding with given dietary Se levels. Model predictions for Atlantic salmon fed plant-based feeds low in natural Se and supplemented with either 0.2 mg of selenite or SeMet kg-1 gave a predicted fillet level of 0.042 and 0.058 mg Se kg-1 wet weight, respectively. Based on these predictions and the European Food Safety Authority risk assessment of Se feed supplementation for food-producing terrestrial farm animals, the supplementation with 0.2 mg of selenite kg-1 would likely be safe for the most sensitive group of consumers (toddlers). However, supplementing feed to farm animals, including salmon, with 0.2 mg of SeMet kg-1 would give a higher (114%) Se intake than the safe upper intake limit for toddlers.

Toxicity of dietary selenomethionine in juvenile steelhead trout, Oncorhynchus mykiss: tissue burden, growth performance, body composition, hematological parameters, and liver histopathology.

The steelhead trout (Oncorhynchus mykiss) is the species most at risk from selenium (Se) exposure in the San Francisco Bay Delta (SFBD). However, although steelhead trout are usually exposed to environmental Se in the juvenile stage, data to test their sensitivity to excess Se, especially its organic form, in the juvenile stage are scarce. Therefore, the objective of the current study was to assess the sensitivity of juvenile steelhead trout to ecologically relevant forms of Se using integrated sensitive endpoints. Fish (mean weight: 22.3 g) were fed one of five diets containing 1.1 (control), 8.8, 15.4, 30.8, and 61.6 µg Se/g diet dw (Se1.1, Se8.8, Se15.4, Se30.8, and Se61.6, respectively) in the form of selenomethionine for 4 weeks. After 4 weeks, Se significantly accumulated in a dose-dependent manner in all tissues at different rates. The growth rate and plasma cholesterol were significantly depressed in fish fed diets containing Se30.8 and above. Hematological parameters and mortality were significantly elevated in fish fed the Se61.6 diet. Marked histopathological alterations were observed in fish fed the Se8.8 diet (the lowest observed effect concentration, LOEC) and above. The current results suggest that the steelhead trout is more sensitive to excess Se than nonanadromous rainbow trout used in previous studies because of its lower LOEC despite the use of selenomethionine and the shorter experimental duration. Additionally, it should be noted that the current Se levels found in the SFBD are already a threat to the threatened population of steelhead trout on the central California coast.

The Effects of Selenomethionine on the Escape Behaviours of Fathead Minnows.

Selenium (Se) is an essential micronutrient for animals and yet becomes toxic with only a small increase in concentration. Toxicological studies have reported various effects of Se on fishes, including developmental impacts and deformities of the musculature and sensory systems. This paper investigates the impact of sublethal concentrations of Se on the ability of the Fathead Minnow (Pimephales promelas) to perform escape responses, a routine behaviour important to predator-prey dynamics. Predation is among the strongest evolutionary driving forces in nature. Changes to this dynamic can have effects that cascade through the ecosystem. We used responses to mechanical and visual stimuli to determine the impact of environmentally relevant concentrations of dietary selenomethionine on the behaviour of minnows. Latency to respond to the stimulus and kinematic performance were assessed. Our results indicated that there was no significant effect of selenomethionine on either the visual response to a threat or burst swimming behaviours of the fast-start response in minnows. Levels of Se in tissues approached that of tissue-specific guidelines set by regulatory bodies across North America. This suggests that current regulations are adequately protecting this key component of predator avoidance in Fathead Minnows.

Impaired Metabolism of Selenomethionine in Graves' Disease: A Biokinetics Study of Soft Gel Capsule Formulation.

Patients with Graves' disease are known to have low selenium (Se) status, Se supplementation resulting in clinical and biochemical improvement. Selenomethionine (SeMet) in a new soft gel capsule formulation was used in a pilot study in 6 patients with acute Graves' disease and low selenium levels (61.3±12.9 µg/l) before and in 4/6 patients 3 months after combined treatment with methimazole and SeMet 200 µg/day (113.3±46.3 µg/l), as well as in 6 euthyroid controls (82±11.8 µg/l). The biokinetics were studied following ingestion of 200 µg SeMet (single dose) soft gel capsule, Se serum concentrations being measured at various time points within 24 h. Se levels rose variably in all patients and controls. While levels peaked in all subjects following 8 h of intake, the increase was somewhat slower in acute hyperthyroidism as compared to 3 months later when these patients had been rendered euthyroid, this possibly due to derangement of Se storage capacity by SEPP or increased requirements in the acute phase of the disease, leading to depletion of the trace element. The compound was shown to be bioavailable and safe and patients treated for 3 months exhibited higher Se levels at the different time points. These findings are of major importance for sufferers of GD since they indicate that early Se supplementation, with its beneficial antioxidant impact on inflammatory activity, could slow, or possibly even forestall, the clinical progression of the disease.

Selenomethionine and methyl selenocysteine: multiple-dose pharmacokinetics in selenium-replete men.

According to the Nutritional Prevention of Cancer (NPC) trial, a selenized yeast supplement containing selenium, 200 mcg/day, decreased the incidence of total cancer, cancers of the prostate, colon and lung, and cancer mortality. The active agent in the selenized yeast supplement was assumed to be selenomethionine (SEMET), although the supplement had not been well speciated. The SELECT study, largely motivated by the NPC trial, enrolling nearly 40 times as many subjects, showed unequivocally that selenium 200 mcg/day, with selenium in the form of SEMET, does not protect selenium-replete men against prostate or other major cancer. The agent tested by SELECT, pure SEMET, could have been different from the selenized yeast tested in NPC. One of the selenium forms suspected of having chemopreventive effects, and which may have been present in the NPC agent, is methyl selenocysteine (MSC). This study, with 29 selenium-replete patients enrolled in a randomized, double-blind trial, compared the multiple-dose toxicity, pharmacokinetics and pharmacodynamics of MSC and SEMET. Patients were on trial for 84 days. No toxicity was observed. Although SEMET supplementation increased blood selenium concentration more than MSC did, neither form had a more than minimal impact on the two major selenoproteins: selenoprotein P(SEPP1) and glutathione peroxidase(GPX).

Effects of Different Forms of Selenium Fertilizers on Se Accumulation, Distribution, and Residual Effect in Winter Wheat-Summer Maize Rotation System.

Foliar Se fertilizers were applied to investigate the effects of Se forms on Se accumulation and distribution in the wheat-maize rotation system and residual concentration of Se in subsequent crops. Sodium selenite, sodium selenate, selenomethionine, chemical nano-Se, humic acid + sodium selenite, and compound fertilizer + sodium selenite were applied once at the flowering stage of wheat (30 g ha-1) and at the bell stage of maize (60 g ha-1). Compared with the control treatment, foliar Se applications significant increased the grain Se concentration of wheat and maize by 0.02-0.31 and 0.07-1.09 mg kg-1, respectively. Wheat and maize grain Se recoveries were 3.0-10.4 and 4.1-18.5%, respectively. However, Se concentrations in the grain of subsequent wheat and maize significantly decreased by 77.9 and 91.2%, respectively. The change of Se concentration in soil was a dynamic process with Se depletion after harvest of maize.

The Effect of Zinc and Selenium Supplementation Mode on Their Bioavailability in the Rat Prostate. Should Administration Be Joint or Separate?

It is thought that zinc and selenium deficiency may play a significant role in the etiology of prostate cancer. Although joint zinc and selenium supplementation is frequently applied in the prevention of prostate diseases, the bioavailability of these elements in the prostate after co-administration is still unknown. The study examines the effect of subchronic supplementation of zinc gluconate and selenium compounds (sodium selenite or selenomethionine), administered together or separately, on their bioavailability in the prostate, as well as the induction of metallothionein-like proteins (MTs) bound to zinc in the prostate and liver. Zinc concentration in the dorso-lateral lobe of the prostate was significantly elevated already after the first month of supplementation of zinc alone. In the supplementation period, the MTs level increased together with zinc concentration. In contrast, the ventral lobe of the prostate did not demonstrate significantly higher levels of zinc until after three months of supplementation, despite the MTs induction noted after one-month supplementation. Increased selenium levels in the dorsolateral lobe were observed throughout the administration and post-administration periods, regardless of the selenium compound used or whether zinc was co-administered. The results of our studies suggested for the first time that these elements should not be administered jointly in supplementation.

Human metabolism and renal excretion of selenium compounds after oral ingestion of sodium selenite and selenized yeast dependent on the trimethylselenium ion (TMSe) status.

A human in vivo metabolism study was carried out to investigate the impact of the trimethylselenium ion (TMSe) status on metabolism and toxicokinetics of sodium selenite and selenized yeast. Nine healthy human volunteers were orally exposed to 200 µg selenium as sodium selenite and seven with selenized yeast (100 µg selenium). In each intervention group, three subjects belong to TMSe eliminators. Blood samples were withdrawn before and up to 6 h after administration. Urine samples were collected before and within 24 h after administration. Total selenium (Se) was quantified in blood plasma and urine and low molecular Se species in urine. Selenium concentration in plasma increased from 84.5 ± 13.2 µg Se/L before to 97.4 ± 13.2 µg Se/L 2-3 h after selenite supplementation and 89.5 ± 12.9 µg Se/L to 92.1 ± 13.9 µg Se/L after selenized yeast intake. The oral ingestion caused an additional Se elimination via urine of 16.9 ± 10.6 µg/24 h (TMSe elim.: 10.8 ± 6.9 µg/24 h; non-TMSe elim.: 20.0 ± 11.3 µg Se/24 h) after selenite exposure and 11.8 ± 4.1 µg/24 h (TMSe elim.: 10.8 ± 4.6 µg/24 h; non-TMSe elim.: 12.6 ± 4.2 µg Se/24 h) after selenized yeast exposure. Methyl-2-acetamido-2-deoxy-1-seleno-ß-D-galactopyranoside (SeSug1) was the main metabolite in all urine samples, whereas TMSe was another main metabolite in TMSe eliminators' urine. After selenite exposure, a small amount of the dose (0.5 ± 0.2 %) was oxidized to selenate and rapidly excreted via urine. With the exception of selenite exposure in TMSe eliminators, the comparison of total Se and the sum of quantified Se species revealed a high renal portion of unidentified species. The study indicated a different metabolism of inorganic and organic Se compounds in human, but also crucial differences of Se metabolism in TMSe eliminators and non-TMSe eliminators.

Gamma camera imaging for studying intestinal absorption and whole-body distribution of selenomethionine.

Se metabolism in humans is not well characterised. Currently, the estimates of Se absorption, whole-body retention and excretion are being obtained from balance and tracer studies. In the present study, we used gamma camera imaging to evaluate the whole-body retention and distribution of radiolabelled selenomethionine (SeMet), the predominant form of Se present in foods. A total of eight healthy young men participated in the study. After consumption of a meal containing 4 MBq [75Se]L-SeMet ([75Se]SeMet), whole-body gamma camera scanning was performed for 45 min every hour over a 6 h period, every second hour for the next 18 h and once on each of the subsequent 6 d. Blood, urine and faecal samples were collected to determine the plasma content of [75Se]SeMet as well as its excretion in urine and faeces. Imaging showed that 87·9 (sd 3·3)% of the administered activity of [75Se]SeMet was retained within the body after 7 d. In contrast, the measured excretion in urine and faeces for the 7 d period was 8·2 (sd 1·1)% of the activity. Time-activity curves were generated for the whole body, stomach, liver, abdomen (other than the stomach and the liver), brain and femoral muscles. Gamma camera imaging allows for the assessment of the postprandial absorption of SeMet. This technique may also permit concurrent studies of organ turnover of SeMet.

Supplementary seleno-L-methionine suppresses active cutaneous anaphylaxis reaction.

To clarify the relationship between selenium supplementation and type I allergic reaction, we investigated the effect of seleno-L-methionine (SeMet) supplementation on the active cutaneous anaphylaxis (ACA) reaction and cytokine production in splenocytes. Female BALB/c mice were sensitized by intraperitoneal injection of ovalbumin (OVA), and SeMet was administered orally for 2 weeks followed by a challenge with OVA to induce an ACA reaction. SeMet supplementation suppressed the ACA reaction in a dose-dependent manner. Plasma OVA-specific immunoglobulin E (IgE) level was strongly inhibited in SeMet-supplemented mice compared with control mice. The mRNA expression levels of the T helper 2 (Th2) cytokines interleukin (IL)-4 and IL-13 in the spleen of SeMet-supplemented mice were lower than those in control mice. The mRNA expression level of a Th1 cytokine, interferon (IFN)-γ, in the spleen of SeMet-supplemented mice was higher than that in control mice. Splenocytes restimulated with OVA in vitro from SeMet-supplemented mice produced lower amounts of IL-4 and IL-13 than those of control mice and higher amounts of IFN-γ than those from the control mice. These results suggest that oral SeMet supplementation suppresses OVA-induced ACA reaction by lowered Th2 cytokine production and augmenting Th1 cytokine production.

Dietary selenomethionine exposure induces physical malformations and decreases growth and survival to metamorphosis in an amphibian (Hyla chrysoscelis).

Selenium (Se) is an essential micronutrient with a narrow therapeutic concentration range. The relative toxicity of Se increases as it is biotransformed into organic compounds, primarily selenomethionine (SeMet), within the aquatic food chain. Effects of aquatic Se contamination are well quantified for many freshwater fish and aquatic bird species, but impacts on amphibians are not well known. This study investigated the responses of larval Cope's gray tree frogs (Hyla chrysoscelis) fed a diet enriched with one of two concentrations of SeMet (50.1 and 489.9 µg Se g(-1) dw [low and high groups, respectively]) by way of a food-limited (ration) or ad libitum (ad lib) feeding regimen. The high dose caused 100 % mortality during the larval period independent of resource provision levels. Regardless of feeding regimen, the low dose decreased larval survival and successful metamorphosis relative to control treatments. The low dose also induced rear limb deformities in ≤73 % of individuals initiating metamorphosis. Providing low-dose food by way of a rationed feeding regimen decreased observed toxicity, likely because of decreased dietary exposure to SeMet relative to the low ad lib treatment. Individuals from the low ration treatment had decreased wet mass at initiation and completion of metamorphic climax (Gosner stages 42 through 46) compared with those from the control ad lib treatment, indicating that resource limitation combined with Se exposure might negatively affect energy stores after metamorphosis. However, lipid content analyses of recently metamorphosed individuals did not reveal any influence of treatment or resource provision on energy stored as lipids. The mean tissue Se concentration of individuals that received the low dose and completed metamorphosis was significantly greater than that of control ad lib or ration individuals at the same developmental stage. This study demonstrates that larval exposure to dietary SeMet can decrease growth and survival and induce deformities in a developing amphibian. Furthermore, retention of Se body burdens through metamorphosis suggests that surviving individuals can transport Se accumulated from contaminated aquatic environments into terrestrial food webs.

Tissue-specific accumulation and speciation of selenium in rainbow trout (Oncorhynchus mykiss) exposed to elevated dietary selenomethionine.

The toxicity of selenium in fish is influenced by its chemical speciation and the exposure route. In the natural environment, selenium exposure to fish occurs primarily in the form of selenomethionine in diet. Thus, the main objective of this study was to examine the tissue-specific selenium burden and speciation in fish exposed to elevated dietary selenomethionine. Rainbow trout (Oncorhynchus mykiss) were treated with dietary selenomethionine (40 µg g(-1) dry mass) for 2 weeks, and at the end of the exposure different tissue samples were collected to assess the tissue-specific distribution and speciation of selenium. We used synchrotron-based X-ray absorption near edge spectroscopy (XANES) to determine the selenium speciation profile. Selenomethionine, selenocysteine and selenocystine were found to be the predominant form of selenium in all of the tissues; however their relative proportion varied across different tissues. In general, the organs primarily involved in selenium handling in fish (e.g., liver, kidney) accumulated a higher percentage of selenocystine. We also found that dietary selenomethionine exposure resulted into a marked increase in selenium burden of all major tissues in fish including the brain. Collectively, our findings provide new insights into the tissue-specific distribution and speciation of selenium in fish exposed to selenomethionine via diet.

Differential responses to selenomethionine supplementation by sex and genotype in healthy adults.

A year-long intervention trial was conducted to characterise the responses of multiple biomarkers of Se status in healthy American adults to supplemental selenomethionine (SeMet) and to identify factors affecting those responses. A total of 261 men and women were randomised to four doses of Se (0, 50, 100 or 200 µg/d as L-SeMet) for 12 months. Responses of several biomarkers of Se status (plasma Se, serum selenoprotein P (SEPP1), plasma glutathione peroxidase activity (GPX3), buccal cell Se, urinary Se) were determined relative to genotype of four selenoproteins (GPX1, GPX3, SEPP1, selenoprotein 15), dietary Se intake and parameters of single-carbon metabolism. Results showed that supplemental SeMet did not affect GPX3 activity or SEPP1 concentration, but produced significant, dose-dependent increases in the Se contents of plasma, urine and buccal cells, each of which plateaued by 9-12 months and was linearly related to effective Se dose (µg/d per kg0·75). The increase in urinary Se excretion was greater for women than men, and for individuals of the GPX1 679 T/T genotype than for those of the GPX1 679 C/C genotype. It is concluded that the most responsive Se-biomarkers in this non-deficient cohort were those related to body Se pools: plasma, buccal cell and urinary Se concentrations. Changes in plasma Se resulted from increases in its non-specific component and were affected by both sex and GPX1 genotype. In a cohort of relatively high Se status, the Se intake (as SeMet) required to support plasma Se concentration at a target level (Se(pl-target)) is: Se(in) = [(Se(pl - target) - Se(pl))/(18.2ng d kg°.75/ml per mu g)] .

In vitro and in vivo percutaneous absorption of seleno-L-methionine, an antioxidant agent, and other selenium species.

AIM: To investigate the in vitro and in vivo percutaneous absorption of seleno-L-methionine (Se-L-M), an ultraviolet (UV)-protecting agent, from aqueous solutions. METHODS: Aqueous solutions of Se-L-M were prepared in pH 4, 8, and 10.8 buffers. The pH 8 buffer contained 30% glycerol, propylene glycol (PG) and polyethylene glycol (PEG) 400. The in vitro skin permeation of Se-L-M via porcine skin and nude mouse skin was measured and compared using Franz diffusion cells. The in vivo skin tolerance study was performed, which examined transepidermal water loss (TEWL), skin pH and erythema. RESULTS: In the excised porcine skin, the flux was 0.1, 11.4 and 8.2 µg·cm(-2)·h(-1) for the pH 4, 8, and 10.8 buffers, respectively. A linear correlation between the flux and skin deposition was determined. According to permeation across skin with different treatments (stripping, delipidation, and ethanol treatments), it was determined that the intracellular route comprised the predominant pathway for Se-L-M permeation from pH 8 buffer. Aqueous solutions of seleno-DL-methionine (Se-DL-M), selenium sulfide and selenium-containing quantum dot nanoparticles were also used as donor systems. The DL form showed a lower flux (7.0 vs 11.4 µg·cm(-2)·h(-1)) and skin uptake (23.4 vs 47.3 µg/g) as compared to the L form, indicating stereoselective permeation of this compound. There was no or only negligible permeation of selenium sulfide and quantum dots into and across the skin. With in vivo topical application for 4 and 8 h, the skin deposition of Se-L-M was about 7 µg/g, and values were comparable to each other. The topical application of Se-L-M for up to 5 d did not caused apparent skin irritation. However, slight inflammation of the dermis was noted according to the histopathological examination. CONCLUSION: Se-L-M was readily absorbed by the skin in both the in vitro and in vivo experiments. The established profiles of Se-L-M skin absorption will be helpful in developing topical products of this compound.

Selenium bioaccumulation and speciation in Chironomus dilutus exposed to water-borne selenate, selenite, or seleno-DL-methionine.

The objective of the present study was to describe the uptake and elimination kinetics of selenium (Se) administered in the forms of selenate, selenite, and selenomethionine (seleno-DL-methionine) in different life stages of the midge Chironomus dilutus, and to determine the relationship between Se bioavailability and Se speciation using X-ray absorption spectroscopy (XAS). Midge larvae exposed to 4.3 µg/L as dissolved selenate for 10 d of had negligible accumulation of Se (indistinguishable from control organisms). However, larvae rapidly accumulated Se over 10 d of exposure to 3.8 and 1.8 µg/L selenite and seleno-DL-methionine (Se-met), respectively. Most Se accumulated by larvae exposed to selenite or Se-met was retained after 10 d of elimination in clean water. When additional midge larvae were exposed to Se until emergence, Se accumulated during the larval stage was largely retained in the adults. Although a strong correlation was found between the adult whole-body Se concentration and the Se concentration in the exuvia after emergence, only a minor loss of Se occurred in the shed exuvia compared with larvae and adult whole-body concentrations. X-ray absorption spectroscopy analysis showed that organic selenides and diselenides, modeled as Se-met and selenocystine, respectively, were the dominant forms of Se in both the larval and adult insect stages. The proportion and concentration of organic selenides (selenomethionine) increased in larvae and adults exposed to Se-met and selenite compared with larvae exposed to selenate, whereas the concentration of diselenides (selenocystine) remained relatively constant for all treatments.

A human model of selenium that integrates metabolism from selenite and selenomethionine.

Selenium (Se) metabolism is affected by its chemical form in foods and by its incorporation (specific vs. nonspecific) into multiple proteins. Modeling Se kinetics may clarify the impact of form on metabolism. Although the kinetics of Se forms have been compared in different participants, or the same participants at different times, direct comparisons of their respective metabolism in the same participants have not been made. The aim of this study was to simultaneously compare kinetics of absorbed Se from inorganic selenite (Sel) and organic selenomethionine (SeMet) in healthy participants (n = 31). After oral administration of stable isotopic tracers of each form, urine and feces were collected for 12 d and blood was sampled over 4 mo. Tracer enrichment was determined by isotope-dilution-GC-MS. Using WinSAAM, a compartmental model was fitted to the data. Within 30 min of ingestion, Se from both forms entered a common pool, and metabolism was similar for several days before diverging. Slowly turning-over pools were required in tissues and plasma for Se derived from SeMet to account for its 3-times-higher incorporation into RBC compared with Se from Sel; these presumably represent nonspecific incorporation of SeMet into proteins. Pool sizes and transport rates were determined and compared by form and gender. The final model consisted of 11 plasma pools, 2 pools and a delay in RBC, and extravascular pools for recycling of Se back into plasma. This model will be used to evaluate changes in Se metabolism following long-term (2 y) Se supplementation.

Effect of dietary selenite on development and intestinal absorption in offspring rats.

AIM: The present study aims to compare selenium (Se) status in offspring rats born to selenium-deficient and selenium supplemented dams and to analyse Se's influence on intestinal parameters and the intestinal absorption of selenomethionine (Se-Met). MAIN METHODS: Male and female Wistar rats (150-200 g) were randomised in: control (C) (0.1 ppm Se), Se-deficient (SD) (0.01 ppm Se) and Se-supplemented (SS) (0.5 ppm Se) groups; and were mated to obtain their offspring. Se levels in serum, urine and faeces in offspring and in mothers' milk were measured by graphite-furnace atomic absorption spectrometry. Duodenal transport studies in offspring were performed using an in vivo perfusion of different Se-Met concentrations (2, 5, 10, 25, 75 and 150 µM). KEY FINDING: A Se-deficient diet provoked a decrease in the offspring's body weight and intestinal parameters, while the supplemented diet increased these values. Serum Se levels were similar between Se-deficient and control offspring because the urinary excretion of Se was smaller to compensate for Se homeostasis. Intestinal Se-Met absorption obeys the Michaelis-Menten equation with lower apparent constant (K(m)) and maximal velocity (V(max)) in the SD group. However, the C and SS groups presented similar K(m) and different V(max). The V(max) showed greater values in the following order of rank: SS>C>SD groups. SIGNIFICANCE: Selenium intake deficiencies in offspring lead to the development of compensatory mechanisms in order to normalise serum selenium levels. These mechanisms, however, do not permit normal body development; nor do they regulate intestinal parameters and Se-Met transport.