This paper looks back on the setting and messages of the review ‘Selenium in Global Food Systems’(1) (see Abstract, Fig. 1) and highlights related findings over the 20 years since its publication. Key papers are cited.

Chronic tubulointerstitial nephropathy (CTIN) is one of the most common kidney diseases. However, treatment for CTIN has multiple limits. Adjuvant therapy through nutritional regulation has become a hot research topic at present. Icariin (ICA), an extraction of Chinese herbal medicine epimedium, has many pharmacological functions including anti-inflammation and tonifying kidney. Selenomethionine (SeMet) possesses the effects of antioxidant and lightening nephrotoxicity. However, little is known about the combined nephroprotection of them. This study was investigated to evaluate the joint effects of ICA and SeMet on CTIN and explore the mechanism. Based on a novel CTIN model developed in our previous study, mice were randomly divided into five groups (a: control; b: model; c: model + ICA; d: model + SeMet; e: model + ICA + SeMet). Renal tubule epithelial cells were treated with cyclosporine A and ochratoxin A without/with ICA or/and SeMet. The results showed that ICA or/and SeMet ameliorated CTIN by inhibiting the uptrends of blood urine nitrogen, serum creatinine, urine protein, urine gravity, histopathological damage degree and collagen I deposition. ICA or/and SeMet also increased cell proliferation and decreased apoptosis and the expression of transforming growth factor-beta 1 and α-smooth muscle actin. Emphatically, ICA and SeMet joint had better nephroprotection than alone in most indexes including fibrosis. Furthermore, ICA and SeMet joint decreased the activation of toll-like receptor 4 (TLR4)/NFκB pathway induced by CTIN. TLR4 overexpression counteracted the joint protection of ICA and SeMet. Therefore, ICA and SeMet in combination could protect against CTIN through blocking TLR4/NFκB pathway. The study will provide novel insights to explore an adjuvant therapeutic orientation.

This study evaluated how different forms of selenium (Se) supplementation into rainbow trout broodstock diets modified the one-carbon metabolism of the progeny after the beginning of exogenous feeding and followed by hypoxia challenge. The progeny of three groups of rainbow trout broodstock fed either a control diet (Se level: 0·3 µg/g) or a diet supplemented with inorganic sodium selenite (Se level: 0·6 µg/g) or organic hydroxy-selenomethionine (Se level: 0·6 µg/g) was cross-fed with diets of similar Se composition for 11 weeks. Offspring were sampled either before or after being subjected to an acute hypoxic stress (1·7 mg/l dissolved oxygen) for 30 min. In normoxic fry, parental Se supplementation allowed higher glutathione levels compared with fry originating from parents fed the control diet. Parental hydroxy-selenomethionine treatment also increased cysteine and cysteinyl–glycine concentrations in fry. Dietary Se supplementation decreased glutamate–cysteine ligase (cgl) mRNA levels. Hydroxy-selenomethionine feeding also lowered the levels of some essential free amino acids in muscle tissue. Supplementation of organic Se to parents and fry reduced betaine-homocysteine S-methyltransferase (bhmt) expression in fry. The hypoxic stress decreased whole-body homocysteine, cysteine, cysteinyl-glycine and glutathione levels. Together with the higher mRNA levels of cystathionine beta-synthase (cbs), a transsulphuration enzyme, this suggests that under hypoxia, glutathione synthesis through transsulphuration might have been impaired by depletion of a glutathione precursor. In stressed fry, S-adenosylmethionine levels were significantly decreased, but S-adenosylhomocysteine remained stable. Decreased bhmt and adenosylmethionine decarboxylase 1a (amd1a) mRNA levels in stressed fry suggest a nutritional programming by parental Se also on methionine metabolism of rainbow trout.

The present study compared the protective effect of sodium selenite (SS) and selenomethionine (SeMet) on heat stress (HS)-invoked porcine IPEC-J2 cellular damage and integrate potential roles of corresponding selenoprotein. Cells were cultured at 37°C until 80 % confluence and then subjected to four different conditions for 24 h: at 37°C (control), 41·5°C (HS), 41·5°C supplied with 0·42 µmol Se/L SS (SS), or SeMet (SeMet). HS significantly decreased cell viability, up-regulated mRNA and protein levels of heat shock protein 70 (HSP70) and down-regulated mRNA and protein levels of tight junction-related proteins (claudin-1 (CLDN-1) and zonula occludens-1 (ZO-1)). HS-induced cell injury was associated with the up-regulation (P < 0·05) of six inflammation-related genes and fourteen selenoprotein encoding genes and down-regulation (P < 0·05) of two inflammation-related genes and five selenoprotein encoding genes. Compared with the HS group, SS and SeMet supplementation resulted in an increase (P < 0·05) in cell viability, decreased (P < 0·05) mRNA expression of HSP70 and six inflammation-related genes and rescue (P < 0·05) of mRNA and protein levels of CLDN-1 and ZO-1. SS and SeMet supplementation changes the expressions of nineteen selenoprotein encoding genes in cells affected by HS. Both Se supplementation significantly recovered the protein level of glutathione peroxidase-1 and increased selenoprotein P in the IPEC-J2 cells under HS, respectively. In summary, Se supplementation alleviated the negative impact of HS on IPEC-J2 cells, and their cellular protective effect was associated with regulation expression of selenoproteins, and SeMet exhibited a better protective effect.

Selenomethionine (SeMet) is an important organic nutritional source of Se, but the uptake and metabolism of SeMet are poorly characterised in humans. Dynamic gamma camera images of the abdominal region were acquired from eight healthy young men after the ingestion of radioactive 75Se-l-SeMet (75Se-SeMet). Scanning started simultaneously to the ingestion of 75Se-SeMet and lasted 120 min. We generated time-activity curves from two-dimensional regions of interest in the stomach, small intestine and liver. During scanning, blood samples were collected at 10-min intervals to generate plasma time-activity curves. A four-compartment model, augmented with a delay between the liver and plasma, was fitted to individual participants’ data. The mean rate constant for 75Se-SeMet transport was 2·63 h–1 from the stomach to the small intestine, 13·2 h–1 from the small intestine to the liver, 0·261 h–1 from the liver to the plasma and 0·267 h–1 from the stomach to the plasma. The delay in the liver was 0·714 h. Gamma camera imaging provides data for use in compartmental modelling of 75Se-SeMet absorption and metabolism in humans. In clinical settings, the obtained rate constants and the delay in the liver may be useful variables for quantifying reduced intestinal absorption capacity or liver function.

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.

Two experiments were conducted on broiler chickens to compare the effect of a new organic Se source, 2-hydroxy-4-methylselenobutanoic acid (HMSeBA; SO), with two practical Se additives, sodium selenite (SS) and Se yeast (SY). The relative bioavailability of the different Se sources was compared on muscle (pectoralis major) total Se, selenomethionine (SeMet) and selenocysteine (SeCys) concentrations and apparent digestibility of total Se (ADSe). In the first experiment, from day (d) 0 to d21, Se sources were tested at different supplied levels and compared with an unsupplemented diet (NC). No significant effects were observed on growth performance during the experimental period. However, the different Se sources and levels improved muscle Se concentration compared with the NC, with a significant source effect in the following order: SS < SY < SO (P< 0·05). Seleno-amino acids speciation results for NC, SY and SO at 0·3 mg Se/kg feed indicated that muscle Se was only present as SeMet or SeCys, showing a full conversion of Se by the bird. The second experiment (d0–d24) compared SS, SY or SO at 0·3 mg Se/kg feed. The ADSe measurements carried out between d20 and d23 were 24, 46 and 49 % for SS, SY and SO, respectively, with significant differences between the organic and mineral Se sources (P< 0·05). These results confirmed the higher bioavailability of organic Se sources compared with the mineral source and demonstrated a significantly better efficiency of HMSeBA compared with SY for muscle Se enrichment.

The objective of this study was to determine the concentration of total selenium (Se) and the proportions of total Se comprised as selenomethionine (SeMet) and selenocysteine (SeCys) in the postmortem tissues of female pheasants (Phasianus Colchicus Torquator) offered diets that contained graded additions of selenised-enriched yeast (SY) or a single comparative dose of sodium selenite (SS). Thiobarbituric acid reactive substances (TBARS) and tissue glutathione peroxidase (GSH-Px) activity of breast (Pectoralis Major) were assessed at 0 and 5 days postmortem. A total of 216 female pheasant chicks were enrolled into the study. Twenty-four birds were euthanased at the start of the study, and samples of blood, breast muscle, leg muscle (M. Peroneus Longus and M. Gastrocnemius), heart, liver, kidney and gizzard were collected for determination of total Se. Remaining birds were blocked by live weight and randomly allocated to one of four dietary treatments (n = 48 birds/treatment) that either differed in Se source (SY v. SS) or dose (control (0.17 mg total Se/kg), SY-L and SS-L (0.3 mg/kg total Se as SY and SS, respectively) and SY-H (0.45 mg total Se/kg)). Following 42 and 91 days of treatment, 24 birds per treatment were euthanased, and samples of blood, breast muscle, leg muscle, heart, liver, kidney and gizzard were retained for determination of total Se and the proportion of total Se comprised as SeMet or SeCys. Whole blood GSH-Px activity was determined at each time point. Tissue GSH-Px activity and TBARS were determined in breast tissue at the end of the study. There were increases in both blood and tissues to the graded addition of SY to the diet (P < 0.001), but the same responses were not apparent with the blood and tissues of selenite-supplemented birds receiving a comparable dose (SY-L v. SS-L). Although there were differences between tissue types in the distribution of SeMet and SeCys, there were few differences between treatments. There were effects of treatment on erythrocyte GSH-Px activity (P = 0.012) with values being higher in treatments SY-H and SS-L when compared with the negative control and treatment SY-L. There were no effects of treatment on tissue GSH-Px activity, which is reflected in the overall lack of any treatment effects on TBARS.

The objective of this study was to determine the concentration of total selenium (Se) and proportions of total Se comprised as selenomethionine (SeMet) and selenocysteine (SeCys) in the tissues of female turkeys offered diets containing graded additions of selenized-enriched yeast (SY), or sodium selenite (SS). Oxidative stability and tissue glutathione peroxidase (GSH-Px) activity of breast and thigh muscle were assessed at 0 and 10 days post mortem. A total of 216 female turkey poults were enrolled in the study. A total of 24 birds were euthanized at the start of the study and samples of blood, breast, thigh, heart, liver, kidney and gizzard were collected for determination of total Se. Remaining birds were blocked by live weight and randomly allocated to one of four dietary treatments (n = 48 birds/treatment) that differed either in Se source (SY v. SS) or dose (Con [0.2 mg/kg total Se], SY-L and SS-L [0.3 mg/kg total Se as SY and SS, respectively] and SY-H [0.45 mg total Se/kg]). Following 42 and 84 days of treatment 24 birds per treatment were euthanized and samples of blood, breast, thigh, heart, liver, kidney and gizzard were retained for determination of total Se and the proportion of total Se comprised as SeMet or SeCys. Whole blood GSH-Px activity was determined at each time point. Tissue GSH-Px activity and thiobarbituric acid reactive substances were determined in breast and thigh tissue at the end of the study. There were responses (P < 0.001) in all tissues to the graded addition of dietary Se, although rates of accumulation were highest in birds offered SY. There were notable differences between tissue types and treatments in the distribution of SeMet and SeCys, and the activity of tissue and erythrocyte GSH-Px (P < 0.05). SeCys was the predominant form of Se in visceral tissue and SeMet the predominant form in breast tissue. SeCys contents were greater in thigh when compared with breast tissue. Muscle tissue GSH-Px activities mirrored SeCys contents. Despite treatment differences in tissue GSH-Px activity, there were no effects of treatment on any meat quality parameter.

Forty multiparous Holstein cows were used in a 16-week continuous design study to determine the effects of either selenium (Se) source, selenised yeast (SY) (derived from a specific strain of Saccharomyces cerevisiae CNCM I-3060) or sodium selenite (SS), or Se inclusion rate in the form of SY in the diets of lactating dairy cows on the Se concentration and speciation in blood, milk and cheese. Cows received ad libitum a total mixed ration (TMR) with a 1 : 1 forage : concentrate ratio on a dry matter (DM) basis. There were four diets (T1 to T4), which differed only in either source or dose of Se additive. Estimated total dietary Se for T1 (no supplement), T2 (SS), T3 (SY) and T4 (SY) was 0.16, 0.30, 0.30 and 0.45 mg/kg DM, respectively. Blood and milk samples were taken at 28-day intervals and at each time point there were positive linear effects of Se in the form of SY on the Se concentration in blood and milk. At day 112, blood and milk Se values for T1 to T4 were 177, 208, 248 and 279 ± 6.6 and 24, 38, 57 and 72 ± 3.7 ng/g fresh material, respectively, and indicate improved uptake and incorporation of Se from SY. In whole blood, selenocysteine (SeCys) was the main selenised amino acid and the concentration of selenomethionine (SeMet) increased with the increasing inclusion rate of SY. In milk, there were no marked treatment effects on the SeCys content, but Se source had a marked effect on the concentration of SeMet. At day 112, replacing SS (T2) with SY (T3) increased the SeMet concentration of milk from 36 to 111 ng Se/g and its concentration increased further to 157 ng Se/g dried sample as the inclusion rate of SY increased further (T4) to provide 0.45 mg Se/kg TMR. Neither Se source nor inclusion rate affected the keeping quality of milk. At day 112, milk from T1, T2 and T3 was made into a hard cheese and Se source had a marked effect on total Se and the concentration of total Se comprised as either SeMet or SeCys. Replacing SS (T2) with SY (T3) increased total Se, SeMet and SeCys content in cheese from 180 to 340 ng Se/g, 57 to 153 ng Se/g and 52 to 92 ng Se/g dried sample, respectively. The use of SY to produce food products with enhanced Se content as a means of meeting the Se requirements is discussed.

The objective was to determine the concentration of total selenium (Se) and the proportion of total Se comprised as selenomethionine (SeMet) and selenocysteine (SeCys) in post mortem tissues of lambs in the 6 weeks period following the withdrawal of a diet containing high-dose selenised yeast (HSY), derived from a specific strain of Saccharomyces cerevisae CNCM (Collection Nationale de Culture de Micro-organism) I-3060. Thirty Texel × Suffolk lambs used in this study had previously received diets (91 days) containing either HSY (6.30 mg Se per kg dry matter (DM)) or an unsupplemented control (C; 0.13 mg Se per kg DM). Following the period of supplementation, all lambs were then offered a complete pelleted diet, without additional Se (0.15 mg Se per kg DM), for 42 days. At enrolment and 21 and 42 days later, five lambs from each treatment were blood sampled, euthanased and samples of heart, liver, kidney and skeletal muscle (longissimus dorsi and psoas major) tissue were retained. Total Se concentration in whole blood and tissues was significantly (P < 0.001) higher in HSY lambs at all time points that had previously received long-term exposure to high dietary concentrations of SY. The distribution of total Se and the proportions of total Se comprised as SeMet and SeCys differed between tissues, treatment and time points. Total Se was greatest in HSY liver and kidney (22.64 and 18.96 mg Se per kg DM, respectively) and SeCys comprised the greatest proportion of total Se. Conversely, cardiac and skeletal muscle (longissimus dorsi and psoas major) tissues had lower total Se concentration (10.80, 7.02 and 7.82 mg Se per kg DM, respectively) and SeMet was the predominant selenised amino acid. Rates of Se clearance in HSY liver (307 μg Se per day) and kidney (238 μg Se per day) were higher compared with HSY cardiac tissue (120 μg Se per day) and skeletal muscle (20 μg Se per day). In conclusion, differences in Se clearance rates were different between tissue types, reflecting the relative metabolic activity of each tissue, and appear to be dependent on the proportions of total Se comprised as either SeMet or SeCys.

In the first part of this review (Surai, 2002), the antioxidant properties and pro-oxidant activity of Se have been described. In spite of a long history, our knowledge of the molecular mechanisms of Se action in human and animals are still in their initial stages. Indeed Se is an integral part of various selenoproteins with glutathione peroxidase (GSH-Px) being the first selenoprotein identified in 1973. Se's participation in antioxidant defence and in the regulation of redox status of the cell could explain its importance to various physiological functions, especially to reproduction. Chicken embryo tissues and spermatozoa are rich in long chain polyunsaturated fatty acids (PUFA) and as a result are very vulnerable to lipid peroxidation. Therefore Se is a crucial factor in maintaining appropriate antioxidant defence during embryonic development and spermatogenesis. In conditions of stress in commercial poultry production the beneficial effects of Se are difficult to overestimate. From egg storage before incubation, when lipid peroxidation can occur, to the final day of egg production, Se participates in preventing the damaging effects of free radicals and toxic products of their metabolism. Dietary antioxidant supplementation in general and organic Se supplementation in particular are considered to be major protective measures for maintaining high productive and reproductive characteristics in poultry.

Selenium (Se) has a special place among the feed-derived natural antioxidants, being an integral part of selenoproteins participating in the regulation of various physiological processes in the body. As a part of glutathione peroxidase (GSH-Px) Se belongs to the first and second major levels of antioxidant defence in the cell. There are two major sources of Se for poultry organic selenium, mainly in the form of selenomethionine (SeMet), which can be found in any feed ingredient in varying concentrations and inorganic selenium, mainly selenite or selenate, which are widely used for dietary supplementation. There is a principal difference in metabolism and efficiency of these two forms of selenium, with SeMet being more effective. In fact SeMet possesses antioxidant properties, however, in some conditions selenite can be a pro-oxidant. Se deficiency and excess in modern poultry production are very rare. In general, adequate Se supplementation is considered to be a crucial factor in maintaining the high productive and reproductive characteristics of commercial poultry.

The bioavailability of Se from ground beef has been previously found in this laboratory to be greater than that of selenite or selenate when fed to female Fischer 344 rats. In the present study we examined the bioavailability of Se from various commercial portions of beef, the liver, striploin, round, shoulder and brisket. All beef was cooked, freeze-dried, finely powdered and mixed with the other dietary ingredients. The experimental diets were fed to the weanling Fischer 344 rats which had been subjected to dietary depletion of Se for 6 weeks. The bioavailability of Se from the beef diets was compared with that of Se as selenite or L-selenomethionine (SeMet) added to torula-yeast diets. Each experimental diet contained 0·10 mg Se/kg. After 8 weeks of dietary Se repletion, relative activity of liver glutathione peroxidase (EC 1·11·1·9; GSHPx) from the different dietary groups compared with that of control animals (100%) was (%): selenite 91, SeMet 122 (P < 0·05), liver 108, striploin 105, round 106, shoulder 106, brisket 103. Se recovery for liver GSHPx was generally highest from SeMet beef muscle = beef liver selenite. Muscle tissue deposition of Se was highest from SeMet beef muscle selenite = beef liver. In addition, the faecal excretion of Se was lowest from the SeMet dietary group and highest from the selenite dietary group. The experimental results suggest that all cuts of beef appear to be highly bioavailable sources of dietary Se when compared with selenite or L-SeMet. Selenjum bioavailability: Beef: Selenite: Selenomethionine