Serum selenium concentrations in neonatal calves: Influence of postnatal selenium injection and health status.

Background: Selenium supply plays a major role in calf rearing, as a deficiency can lead to health problems, economic loss, and even death. Therefore, postnatal selenium injections are often administered as a preventive measure. Objective: In this study, we examined the serum selenium concentrations of healthy and sick calves within the first days of life. Further, serum concentrations after injection with selenium were determined. Animals and procedure: Serum selenium concentrations from 75 calves were measured until the 10th d of life and the differences between sick and healthy calves were investigated. The variations in selenium concentration were analyzed 3 and 6 d after subcutaneous injection of 5.5 mg sodium selenite in 32 calves.To compare serum concentrations between healthy and sick calves, an independent samples t-test was used. For unequal variances, the Satterthwaite method was used; and for equal variances, the pooled sample variance was used. To analyze the statistical differences between the concentrations at different time points, the data were log-transformed and the Bonferroni correction was used. Results: The mean initial selenium concentration was 46 ± 37 µg/L. There was no statistically significant difference (P = 0.60) between sick (46 ± 34 µg/L) and healthy (46 ± 47 µg/L) calves. Serum selenium concentrations 3 and 6 d after injection of calves over 3 samples were 62 ± 19 µg/L and 50 ± 13 µg/L, respectively. Calves with an initial serum concentration of ≥ 72 µg/L showed a decrease of serum selenium concentration despite the injection. Conclusion and clinical relevance: Newborn calves showed a high variation in selenium concentration that was not influenced by health status. A single injection of 5.5 mg of sodium selenite did increase the selenium concentration in calves with selenium undersupply. After injection, none of the calves showed serum concentrations above the reference range for adult cattle. Therefore, the indication for a selenium injection can be interpreted generously if selenium undersupply is suspected.

Concentrations sériques de sélénium chez les veaux nouveau-nés : influence de l'injection postnatale de sélénium et de l'état de santé. Contexte: L'apport en sélénium joue un rôle majeur dans l'élevage des veaux, car une carence peut entraîner des problèmes de santé, des pertes économiques et même la mort. Par conséquent, des injections postnatales de sélénium sont souvent administrées à titre préventif. Objectif: Dans cette étude, nous avons examiné les concentrations sériques de sélénium de veaux sains et malades au cours des premiers jours de vie. De plus, les concentrations sériques après injection de sélénium ont été déterminées. Animaux et procédure: Les concentrations sériques de sélénium de 75 veaux ont été mesurées jusqu'au 10e jour de vie et les différences entre les veaux malades et sains ont été étudiées. Les variations de concentration en sélénium ont été analysées 3 et 6 jours après l'injection sous-cutanée de 5,5 mg de sélénite de sodium chez 32 veaux.Pour comparer les concentrations sériques entre les veaux sains et malades, un test t sur échantillons indépendants a été utilisé. Pour les variances inégales, la méthode de Satterthwaite a été utilisée; et pour des variances égales, la variance de l'échantillon groupé a été utilisée. Pour analyser les différences statistiques entre les concentrations à différents moments, les données ont été transformées par logarithme et la correction de Bonferroni a été utilisée. Résultats: La concentration initiale moyenne en sélénium était de 46 ± 37 µg/L. Il n'y avait pas de différence statistiquement significative (P = 0,60) entre les veaux malades (46 ± 34 µg/L) et sains (46 ± 47 µg/L). Les concentrations sériques de sélénium 3 et 6 jours après l'injection des veaux sur 3 échantillons étaient respectivement de 62 ± 19 µg/L et de 50 ± 13 µg/L. Les veaux avec une concentration sérique initiale ≥ 72 µg/L ont montré une diminution de la concentration sérique en sélénium malgré l'injection. Conclusion et pertinence clinique: Les veaux nouveau-nés ont montré une forte variation de la concentration en sélénium qui n'était pas influencée par l'état de santé. Une injection unique de 5,5 mg de sélénite de sodium a augmenté la concentration de sélénium chez les veaux présentant un apport insuffisant en sélénium. Après l'injection, aucun veau n'a présenté de concentrations sériques supérieures à la plage de référence pour les bovins adultes. Par conséquent, l'indication d'une injection de sélénium peut être interprétée de manière généreuse si un apport insuffisant en sélénium est suspecté.(Traduit par Dr Serge Messier).

Comparative oral dose toxicokinetics of sodium selenite and selenomethionine.

Selenium (Se) poisoning by different forms of Se occurs in the United States. However, the toxicokinetics of different selenocompounds after oral ingestion is not well documented. In this study the toxicokinetics of Se absorption, distribution and elimination were determined in serum and whole blood of lambs that were orally dosed with increasing doses of Se as sodium selenite (inorganic Se) or selenomethionine (SeMet, organic Se). Thirty-two lambs were randomly assigned to eight treatment groups, with four animals per group. Se was administered at 1, 2 or 3 mg kg-1 body weight, as either sodium selenite or SeMet with proper control groups. Blood and serum were collected at predetermined time points for 7 days post-dosing. Resulting Se concentrations in both serum and whole blood from SeMet treatment groups were significantly greater than those given equimolar doses of Se as sodium selenite. Se concentrations in serum and whole blood of lambs dosed with SeMet peaked at significantly greater concentrations when compared with lambs dosed with equimolar doses of sodium selenite. Based on the serum and whole blood kinetics, the rate of Se absorption was greater for SeMet than for sodium selenite although rates of absorption for both Se forms decreased with increasing dose. The rates of Se elimination increased with dose. These results demonstrate that SeMet has a greater absorption rate and a similar retention time resulting in a greater area under the curve and thus bioavailability than sodium selenite, which must be considered in both overdose and nutritional exposures. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Selenite supplementation in euthyroid subjects with thyroid peroxidase antibodies.

CONTEXT: Euthyroid thyroid peroxidase (TPO-Ab)-positive subjects are at risk for progression to subclinical and overt autoimmune hypothyroidism. Previous studies have shown a decrease in TPO-Ab and improvement of quality-of-life (QoL) in L-T4-treated hypothyroid patients upon selenium supplementation. OBJECTIVES: To evaluate in euthyroid TPO-Ab-positive women without thyroid medication whether selenite decreases TPO-Ab and improves QoL. DESIGN: Randomized, placebo-controlled, double-blind study. PATIENTS AND METHODS: Euthyroid (TSH 0·5-5·0 mU/l, FT4 10-23 pm) women with TPO-Ab ≥ 100 kU/l were randomized to receive 200 mcg sodium selenite daily (n = 30) or placebo (n = 31) for 6 months. TSH, FT4, TPO-Ab, selenium (Se), selenoprotein P (SePP) and QoL were measured at baseline, 3, 6 and 9 months. RESULTS: There were no differences in baseline characteristics between the Se group and the placebo group. During selenite supplementation, serum Se and SePP did not change in the placebo group, but increased in the Se group. TPO-Ab and TSH did not change significantly in any group. TPO-Ab in the Se group were 895 (130-6800) at baseline, 1360 (60-7050) kU/l at 6 months, in the placebo group 1090 (120-9200) and 1130 (80-9900) kU/l, respectively (median values with range). TSH in the Se group was 2·1 (0·5-4·3) at baseline, 1·7 (0·0-5·3) mU/l at 6 months, in the placebo group 2·4 (0·7-4·4) and 2·5 (0·2-4·3) mU/l, respectively. QoL was not different between the groups. CONCLUSION: Six months selenite supplementation increased markers of selenium status but had no effect on serum TPO-Ab, TSH or quality-of-life in euthyroid TPO-Ab-positive women.

Simultaneous analysis of mercury and selenium species including chiral forms of selenomethionine in human urine and serum by HPLC column-switching coupled to ICP-MS.

The simultaneous speciation of elements is of great concern, especially in the study of the interactions of species in living organisms. Here we report a method based on the coupling of HPLC-ICP-MS that is capable of separating and analyzing different selenium and mercury species (Se-methylselenocysteine, selenite, selenate, L-selenomethionine, D-selenomethionine, methylmercury and inorganic mercury). The proposed method uses two different mobile phases that are suitable for selenium and mercury speciation and leads to a successful determination of all the species in less than 27 min with good efficiency and resolution. The method was efficiently applied for simultaneous speciation of mercury and selenium in urine and in serum, the latter from umbilical cord samples. Selenocystine has been successfully identified in the former sample. Detection limits obtained were between 0.30 and 2.46 ng. Recovery studies of samples spiked with all species were performed to check the reliability of the method, and satisfactory recoveries (93-110%) were obtained in all cases. The relative standard deviations (RSDs) for species with ten replicate determinations of 80 µg L(-1) were between 4.5 and 9.2%. The proposed method offers a deeper insight into selenium and mercury interactions in the human body.

Pharmacokinetics of Sodium Selenite in Rat Plasma and Tissues After Intragastric Administration.

The purpose of this research is to investigate the absorption, distribution, excretion, and pharmacokinetics of selenite in rats after intragastric administration, and thus illustrate the efficiency of selenium (Se) supplementation. After a single gavage of sodium selenite, a concentration of Se in plasma and tissues was determined by inductively coupled plasma mass spectrometry (ICP-MS) at different time points. Through fitting the data with the metabolic kinetic model, the corresponding kinetic parameters were determined for plasma and tissues, including kidney, liver, heart, muscle, and gonad. While the metabolic kinetics of sodium selenite in plasma, liver, and kidney of rats was well reflected by a two-compartment open model, that in heart and gonad was fitted to a one-compartment open model, and that in muscle was fitted to a one-compartment open model with a lag time. The results indicate that sodium selenite was absorbed by plasma and tissues quickly and was eliminated slowly after intragastric administration. Based on the results, we propose that multi-supplementation of Se with low dosage is superior to single supplementation with high dosage, in terms of avoiding selenosis.

Comparison of Bioavailability, Pharmacokinetics, and Biotransformation of Selenium-Enriched Yeast and Sodium Selenite in Rats Using Plasma Selenium and Selenomethionine.

For the first time, bioavailability, pharmacokinetics, and biotransformation of selenium-enriched yeast (SeY) and sodium selenite (Na2SeO3) in rats were systemically compared by analyzing free selenomethionine (SeMet), total SeMet, and selenium (Se). After SeY and Na2SeO3 were orally administered to rats at a dose of 100 µg Se/kg, plasma free SeMet, total SeMet, and Se at various time points were determined by ultra-performance liquid chromatography-tandem mass spectrometry. Based on Se and total SeMet, the relative bioavailability values of SeY compared with Na2SeO3 were 144% and 272%, respectively. For the rats treated with SeY, 0.73-2.68% of total Se was biotransformed to free SeMet, 14.3-20.4% to SeMet-proteins and albumin-bound SeMet, and 75.9-82.3% to selenoproteins in plasma. SeY had higher bioavailability than Na2SeO3 based on Se and total SeMet levels. Plasma SeMet was the optimal biomarker of SeY status in vivo.

Co-administration of Selenium with Inorganic Mercury Alters the Disposition of Mercuric Ions in Rats.

Mercury (Hg) is a common environmental toxicant to which humans are exposed regularly through occupational and dietary means. Although selenium supplementation has been reported to prevent the toxic effects of Hg in animals, the mechanisms for this prevention are not well understood. The purpose of the current study was to determine the effects of selenium on the disposition and toxicity of Hg. Wistar rats were injected intravenously with a non-nephrotoxic dose (0.5 µmol kg-1) or a nephrotoxic dose (2.5 µmol kg-1) of HgCl2 (containing radioactive Hg) with or without co-administration of sodium selenite (Na2SeO3). Twenty-four hours after exposure, rats were euthanized, and organs were harvested. Co-administration of SeO32- with HgCl2 reduced the renal burden of Hg and the urinary excretion of Hg while increasing the amount of Hg in blood and spleen. We propose that Hg reacts with reduced selenite in the blood to form large Hg-Se complexes that are unable to be filtered at the glomerulus. Consequently, these complexes remain in the blood and are able to accumulate in blood-rich organs. These complexes, which may have fewer toxic effects than other species of Hg, may be eliminated slowly over the course of weeks to months.

Selenium Ameliorates Ibuprofen Induced Testicular Toxicity by Redox Regulation: Running Head: Se protects against NSAID induced testicular toxicity.

Despite the Cox inhibitory anti-inflammatory and antipyretic effects of most widely used non-steroidal anti-inflammatory drugs (NSAIDs), such as Ibuprofen, their chronic use is associated with a plethora of patho-physiological insults. One such toxic effect on testicular tissues is not well studied and the underlying molecular mechanisms remain unexplored. Thus, the current study is designed to evaluate the antioxidant properties of essential trace element selenium (Se) to ameliorative Ibuprofen associated testicular toxic effects. Adult male Wistar rats were divided into 3 groups and fed on diets containing different concentrations of sodium selenite, viz. 0.01 mg/kg (Se- deficient), 0.2 mg/kg (Se-adequate), or 0.5 mg/kg (Se- supplemented) for 8 weeks. After diet feeding schedule, each group was divided into two subgroups i.e., with or without the treatment of Ibuprofen (120 mg/kg Bw). The protective effect of Se was evaluated by measuring testicular Se and selenoproteins status, spermatogenic markers, histopathology and testicular redox status. Ibuprofen diminished seminal volume, sperm count, sperm motility, which correlated well increased testicular reactive oxygen species. Se deficiency exacerbated these detrimental effects of ibuprofen by increasing oxidative stress. Alternatively, Se supplementation through antioxidant enzymes mediated protective effects. Se as essential antioxidant selenoproteins ameliorates Ibuprofen induced male reproductive toxicity.

Pharmacokinetics of Sodium Selenite Administered Orally in Blood and Tissues of Selenium-Deficient Ducklings.

Selenium (Se) is an essential trace element for humans and animals. Appropriate amount of Se in the body can prevent a variety of diseases. However, Se deficiency leads to pathological changes such as skeletal muscle necrosis and pancreatic atrophy in livestock and poultry. Se preparations are widely used in the prevention and treatment of Se-deficient disease, but there is no unified standard of medication, and the safe dose range of Se is narrow. Therefore, it is of great significance to study the pharmacokinetics of low-Se ducklings and to formulate drug administration schemes. In the present study, eighty 1-day-old healthy ducklings were randomly selected, and fed with low-Se diet to 30 days of age (blood Se content ≦ 0.03 µg/mL). After the low Se duckling models were duplicated, blood samples and tissues of livers, pancreases, and thigh muscles were collected at different time points to detect Se content following oral administration of 0.1% sodium selenite (Na2SeO3) at 0.8 mg/kg BW, and the pharmacokinetics parameters were automatically calculated by MCPKP program. The results showed that pharmacokinetics characteristics of Na2SeO3 in blood, livers, and pancreases of ducklings were consistent with the first-order absorption and two-compartment open models; in thigh muscles was consistent with the first-order absorption and one compartment with a lag time open model. The primary kinetic parameters of Na2SeO3 in blood: the half-life of absorption was 5.9026 h, the time of reaching maximum concentration was 23.03 h, and the half-life of elimination was 131.13 h. The absorption of Na2SeO3 in livers was the quickest, pancreases and thigh muscles were in order of becoming slower, and the elimination of Na2SeO3 in thigh muscles was the quickest, livers and pancreases were in order of becoming slower. The administration parameters of multi-dose were calculated according to the kinetic of single-dose: loading dose (D*) was 1.7046 mg/kg BW, maintenance dose (D0) was 0.8 mg/kg BW, and dosing interval (τ) was 120 h. The results of this study can supplement and improve the theoretical system of Se metabolic kinetics, and provide experimental basis for the prevention and treatment of Se deficiency disease by rational drug use.

Injectable organic and inorganic selenium in dairy cows - Effects on milk, blood and somatic cell count levels.

Mastitis is the most costly disease of dairy cows. A pro-active approach includes insuring adequate levels of selective trace minerals. The aim of this study was to determine the effect of two different commercially available, injectable selenium products, (sodium) Na-selenite (inorganic) and (selenium) Se-methionine (organic), on milk composition and on serum and milk selenium concentrations in high-yielding Holstein cows on total mix ration. Sixty multiparous cows were randomly selected into three groups of 20, one control group and two groups supplemented with injectable trace minerals. Blood and milk samples were collected over a period of 60 days. No specific change was indicated in milk yield, lactose, milk urea nitrogen (MUN) and milk pH levels compared with baseline values. The Se-methionine supplemented group showed a numerical increase in total milk protein percentage. In the group injected with Se-methionine, a negative correlation was present for the initial 72 hours between serum selenium concentration and somatic cell count (SCC) and a highly significant (p 0.001) increase in milk selenium concentration for the initial 24 hours. Serum selenium concentration of Se-methionine-supplemented cows was however not significantly changed. Injection of Na-selenite led to a 60-day initial increase in serum selenium concentration above baseline levels and a significant milk selenium concentration on day 1 but to a negative correlation between serum selenium concentration and SCC. Differences in serum and milk selenium concentrations followed with the use of organic and inorganic selenium injectables. Injectable Na-selenite, as selenium, can be of important value for cattle farmers if supplemented on strategically physiological periods to improve production, reproduction and immunity.

Effects of sodium selenite and L-selenomethionine on feed intake, clinically relevant blood parameters and selenium species in plasma, colostrum and milk from high-yielding sows.

A field study in periparturient sows fed different dietary concentrations of either sodium selenite or L-selenomethionine (SeMet) was conducted to evaluate feed intake, haematological and biochemical parameters as well as to describe some key selenium (Se) species, namely selenoprotein P (SelP), selenoalbumin (SeAlb) and selenomethionine (SeMet) as well as total Se in plasma, colostrum and milk. Thirty-two sows were allotted to four treatments from 30 days (d) prepartum throughout on average a 32 d lactation period. Sodium selenite supplemented diets contained 0.40 and 0.60 mg Se/kg feed, while SeMet supplemented feed contained 0.26 and 0.43 mg Se/kg feed. Concentrations of sodium selenite and SeMet in complete feed exceeded the upper limits for total dietary Se and added organic Se, respectively, according to the European Union legislation. Blood samples were collected at initiation of the study, at farrowing and at weaning. Colostrum samples were collected at farrowing and milk samples at weaning. Se species were subjected to liquid chromatography, and total Se and Se species were determined using inductively coupled plasma mass spectrometry. The SeMet supplemented diets resulted in higher feed intake and in higher levels of total Se, SelP, SeAlb and SeMet in colostrum compared with sows fed sodium selenite. Similar results were obtained for levels of total Se and SeMet in milk at weaning. The higher dietary sodium selenite concentration in sows' feed did not increase the Se transfer into colostrum or milk when compared with those receiving the lower level of sodium selenite. However, the increase in serum-Zn from initiation until farrowing, observed in sows fed SeMet as well as the higher glutamate dehydrogenase activity in sodium selenite supplemented sows in this period might indicate a higher requirement of antioxidant defence in sodium selenite-supplemented sows. To our knowledge, the present data on Se species in plasma, colostrum and milk of sows represent the most complete investigation of Se in sows conducted to date. A higher amount of the above-mentioned Se species in the colostrum of sows supplemented with SeMet might strengthen the piglets' antioxidative system and passive immunity as well as improve their average daily weight gain. The higher feed intake in sows fed diets supplemented with SeMet is an interesting finding that warrants further investigation.

Relative bioavailability of ultrafine sodium selenite for broilers fed a conventional corn-soybean meal diet.

The particle size of selenium (Se) sources could affect Se absorption and utilization, and thus it is hypothesized that the Se bioavailability might be higher in ultrafine sodium selenite (USSe) than in sodium selenite (SSe) for broilers because of USSe's smaller particle size. An experiment was conducted to investigate the relative bioavailability of Se as USSe relative to SSe for broiler chicks fed a conventional corn-soybean meal diet. A total of 504 one-d-old Arbor Acres commercial male broilers were randomly allotted to 1 of 7 treatments with 6 replicates per treatment in a completely randomized design involving in a 2 (Se sources) × 3 (added Se levels) factorial arrangement of treatments plus a Se-unsupplemented control diet containing 0.05 mg Se/kg by analysis for 21 d. The 2 Se sources were USSe and SSe, and the 3 added Se levels were 0.15, 0.30, or 0.45 mg Se/kg. The Se concentrations, glutathione peroxidase (GSH-Px) activities, and mRNA relative abundances in plasma, liver, or pancreas of broilers on day 14 and 21 were determined. The results showed that Se concentrations, GSH-Px activities in plasma, liver, and pancreas, and mRNA relative abundances in the liver and pancreas of broilers on day 14 and 21 increased linearly (P < 0.05) as the added Se-level increased. Furthermore, a difference (P < 0.05) between USSe and SSe was detected for GSH-Px mRNA relative abundance in the pancreas of broilers on day 14. On the basis of the slope ratios from the multiple linear regression of the pancreatic GSH-Px mRNA relative abundance of broilers at 14 d of age on daily dietary analyzed Se intake, the Se bioavailability of USSe relative to SSe (100%) was 158% (P < 0.05). The results from this study indicated that the Se from USSe was more available to broilers than the Se from SSe in enhancing the pancreatic GSH-Px mRNA expression.

Effects of different selenium sources on tissue selenium concentrations, blood GSH-Px activities and plasma interleukin levels in finishing lambs.

Thirty-two wether lambs of Tan sheep were randomly assigned into four dietary treatment groups (eight per group) for an 8-wk study and then fed a basal diet deficient in Se (0.06 mg/kg) or diets supplemented to provide 0.10 mg/kg Se from sodium selenite, selenized yeast, and seleniumenriched probiotics, respectively. Blood samples were collected at d 0, 28, and 56 of the experiment and tissue samples were collected at experiment termination. Tissue and blood Se concentrations, blood glutathione peroxidase (GSH-Px) activities, and plasma interleukin levels were analyzed. The results showed that the concentrations of Se in the kidney, liver, and muscle increased in all of the supplemented groups (p < 0.01) compared with the control group. However, the Se concentrations in the kidney, liver, and muscle in the groups supplemented with Se yeast and Se-enriched probiotics were higher than those in the group supplemented with sodium selenite (p < 0.01). The activities of GSH-Px and the concentrations of Se in blood also increased in all of the supplemented groups during the period of supplementation (p < 0.01) compared with the control group. The activities of GSH-Px and the concentrations of Se in the whole blood of the lambs fed with selenized yeast and Se-enriched probiotics were higher than those of lambs fed with sodium selenite (p<0.01 or p<0.05). The concentrations of interleukin-1 and interleukin-2 in plasma significantly increased in all of the supplemented groups during the entire period of experiment (p<0.01) compared with the control group, but had no significant differences among all of the supplemented groups. In conclusion, a diet supplemented with Se for finishing lambs was able to increase the concentrations of Se in tissue and blood, activities of GSH-Px in blood, and levels of interleukins in plasma. Organic Se sources (selenized yeast and Se-enriched probiotics) were more effective than the inorganic Se source (sodium selenite) in increasing tissue and blood Se concentrations and blood GSH-Px activities of lambs. However, there were no significant differences in plasma interleukin levels of lambs between organic and inorganic Se sources.

Pharmacokinetics and Toxicity of Sodium Selenite in the Treatment of Patients with Carcinoma in a Phase I Clinical Trial: The SECAR Study.

BACKGROUND: Sodium selenite at high dose exerts antitumor effects and increases efficacy of cytostatic drugs in multiple preclinical malignancy models. We assessed the safety and efficacy of intravenous administered sodium selenite in cancer patients' refractory to cytostatic drugs in a phase I trial. Patients received first line of chemotherapy following selenite treatment to investigate altered sensitivity to these drugs and preliminary assessment of any clinical benefits. MATERIALS AND METHODS: Thirty-four patients with different therapy resistant tumors received iv sodium selenite daily for consecutive five days either for two weeks or four weeks. Each cohort consisted of at least three patients who received the same daily dose of selenite throughout the whole treatment. If 0/3 patients had dose-limiting toxicities (DLTs), the study proceeded to the next dose-level. If 2/3 had DLT, the dose was considered too high and if 1/3 had DLT, three more patients were included. Dose-escalation continued until the maximum tolerated dose (MTD) was reached. MTD was defined as the highest dose-level on which 0/3 or 1/6 patients experienced DLT. The primary endpoint was safety, dose-limiting toxic effects and the MTD of sodium selenite. The secondary endpoint was primary response evaluation. RESULTS AND CONCLUSION: MTD was defined as 10.2 mg/m(2), with a calculated median plasma half-life of 18.25 h. The maximum plasma concentration of selenium from a single dose of selenite increased in a nonlinear pattern. The most common adverse events were fatigue, nausea, and cramps in fingers and legs. DLTs were acute, of short duration and reversible. Biomarkers for organ functions indicated no major systemic toxicity. In conclusion, sodium selenite is safe and tolerable when administered up to 10.2 mg/m(2) under current protocol. Further development of the study is underway to determine if prolonged infusions might be a more effective treatment strategy.

Interferon/antioxidant combination therapy for chronic hepatitis C--a controlled pilot trial.

The effects of two forms of antioxidative co-therapy were analyzed in 24 interferon-alpha (IFN)-naive patients with chronic hepatitis C who were randomized to either receive IFN monotherapy (3 x 4.5 million units IFN-alpha 2a per week), (group A), or IFN and N-acetylcysteine (N-acetylcysteine (NAC) 1.800 mg/day) plus sodium selenite (400 microg/day) supplementation (group B), or treatment as in group B plus vitamin E (544 IU/day) (group C), over 24 weeks. Changes in histology, normalization of ALT, reduction of viral RNA, serum levels of glutathione, selenium, vitamin E, erythrocyte glutathione peroxidase, trolox equivalent antioxidative capacity (TEAC), thiobarbituric acid reactive substances (TBARS) and protein carbonyl groups were measured. Low baseline TEAC and elevated TBARS indicated increased oxidative stress before therapy, which was not affected by antioxidant supplementation. At the end of treatment complete responses were found in 3/8, 2/8 and 6/8 patients in groups A, B and C, respectively, but liver histology had not significantly improved. Vitamin E treated patients had a 2.4 greater chance (95% CI: 1.05-5.5) of obtaining a complete response and had significantly greater reduction in viral load (P = 0.028) than patients without vitamin E. Relapses, i.e. re-appearance of detectable hepatitis C virus (HCV) RNA and/or re-elevation of ALT-activity occurred in 7 out of the 11 responders within 6 months after termination of therapy (group A: 2/3, group B: 1/2 and group C: 4/6). Thus, no overall beneficial effect of antioxidant/IFN therapy was detected. However, the apparent trend towards a more favorable outcome with vitamin E supplementation warrants to further study this substance as an adjuvant to IFN therapy in chronic hepatitis C.

Effects of arsenic-, platinum-, and gold-containing drugs on the disposition of exogenous selenium in rats.

Having found that the electrophilic model compound sulfobromophthalein markedly altered the fate of exogenous selenium in the body by reacting in vivo with nucleophilic selenium metabolites, the effects of metal-containing drugs with expected selenium reactivity were tested on biliary, urinary, and pulmonary excretion. Tissue distribution of selenium in selenite-injected rats was also examined. Coadministration with [(75)Se]selenite (10 micromol/kg, iv) of the trypanosomicid arsenicals (100 micromol/kg, iv) trimelarsan (TMA) or melarsoprol (MAP), the antitumor cisplatin (25 micromol/kg, iv), or the antirheumatic gold sodium thiomalate (25 or 50 micromol/kg, iv) significantly altered the disposition of (75)Se, whereas carboplatin (100 micromol/kg, iv) did not produce such an effect. The most dramatic alterations included the approximately 20-fold increase in the biliary excretion rate of selenium in response to TMA and MAP, the almost complete cessation of the exhalation of selenium as dimethyl selenide after administration of the arsenic- and gold-containing drugs, and the manifold accumulation of selenium in the blood plasma following gold injection. Direct chemical reaction of the drugs with nucleophilic selenite metabolites in the body may underlie these alterations. The tight coordination in time and extent observed between the biliary excretion of arsenic and selenium in rats receiving either of the arsenicals and selenite supports this hypothesis. However, attempts to detect selenium-containing biliary metabolites of TMA and MAP have failed, possibly owing to their instability. In summary, the arsenic-, platinum- and gold-containing drugs significantly influence the fate of exogenous selenium, whereby they may adversely affect the availability of this essential element for synthesis of selenoenzymes. Furthermore, the capability of TMA and MAP to enhance the biliary and total excretion of selenium renders these drugs significant candidates for antidotes in selenium intoxication.

Effect of dietary selenite on N-nitrosodiethylamine-induced and phenobarbital promoted multistage hepatocarcinogenesis in rat: reflection in some minerals.

Selenium (Se), a dietary micronutrient, plays a vital role in cancer chemotherapy in many organs including the liver. We have studied the relationship between some minerals, which are essential in normal functioning of cells and anticancer effect of Se in N-nitrosodiethylamine (DEN) induced and phenobarbital (PB) promoted multistage hepatocarcinogenesis. Se (4 ppm through drinking water; as sodium selenite) was given to animals throughout the study, before initiation and during promotion phase of hepatocarcinogenesis, in a defined experimental protocol. Se, sodium, potassium, calcium and iron were measured either in hepatoma, or surrounding liver tissue or whole liver tissue and serum of experimental animals. DEN and PB treatment significantly (P < 0.001) increased potassium, calcium and iron levels in serum, while it decreased (P < 0.001) the Se and sodium levels when compared with control rats. We have also observed significantly increased (P < 0.001) sodium, calcium and iron levels in hepatoma and surrounding liver tissue, whereas, Se, and potassium level was found to be decreased (P < 0.001) when compared with control rats. Supplementation of selenite throughout the study, before initiation and during promotion stage significantly alters the above mineral content. Results showed that the most significant beneficial effect of selenium during hepatocarcinogenesis was exerted potentially in long-term continuous and/or before the initiation phase of carcinogenicity, rather than in the promotion phase. The present and previous results from our laboratory suggest that sub-optimal intake of a single trace mineral can have broad effects on chemotherapy, providing a framework for understanding the multiple beneficial effects of selenium in cancer chemoprevention.

Evaluation of the efficacy of 2-hydroxy-4-methylselenobutanoic acid on growth performance and tissue selenium retention in growing pigs.

The aim of this study was to compare the efficacy of a new organic Se (2-hydroxy-4-methylselenobutanoic acid [HMSeBA]) source (SO) with sodium selenite (SS) and selenized yeast (SY) at various dietary levels for growth performance and tissue Se deposition in growing pigs. A total of 112 crossbred (Pietrain × [Large White × Landrace]) gilts were allotted at an average body weight of 26.73 kg to 7 dietary treatments with 8 replicate pens of 2 pigs per pen. Pigs were fed basal diets unsupplemented or supplemented either with SS, SY, or SO each at 0.1 or 0.3 mg Se/kg of diet for 32 d. Feed intake and BW were recorded during the experimental period. At the end of the experiment, blood, liver, and psoas major muscle of all gilts were collected for total Se and relative bioavailability determination. No differences were observed on final BW, ADG, ADFI, and G:F among dietary treatments. All Se-supplemented groups exhibited greater total Se contents in plasma (P < 0.01) and liver (P < 0.01) compared with unsupplemented control group. However, Se retention in psoas major muscle was improved only when organic Se source (SY or SO) was added to diets (P < 0.01). Regardless the Se level, the Se deposition in muscle was greater (P < 0.01) in pigs supplemented with SO than those supplemented with SY. Slope ratio assay confirmed the greater bioavailability of Se from organic compared with inorganic Se and also revealed that the relative bioavailability of Se from HMSeBA for plasma, liver, and muscle Se response was 170, 141, and 162%, respectively, for SY. This study shows a potential advantage of HMSeBA supplementation in the increase of Se contents in pig tissues, indicating that this new organic Se source could be an alternative source of Se in swine nutrition.

Effects of dietary selenium supplementation on tissue selenium distribution and glutathione peroxidase activity in Chinese Ring necked Pheasants.

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.

Organic and inorganic selenium: I. Oral bioavailability in ewes.

Although the essentiality of dietary Se for sheep has been known for decades, the chemical source and Se dosage for optimal health remain unclear. In the United States, the Food and Drug Administration (FDA) regulates Se supplementation, regardless of the source of Se, at 0.3 mg of Se/kg of diet (as fed), which is equivalent to 0.7 mg of Se/d or 4.9 mg of Se/wk per sheep. The objectives of this study were to evaluate the effects of Se source (inorganic vs. organic) and supplementation rate (FDA vs. supranutritional rates of 14.7 and 24.5 mg of Se/wk) on whole-blood (WB) and serum-Se concentrations. Mature ewes (n = 240) were randomly assigned to 8 treatment groups (n = 30 each) based on Se supplementation rate (4.9, 14.7, and 24.5 mg of Se•wk(-1)•sheep(-1)) and source [Na-selenite, Na-selenate (4.9 mg/wk only), and organic Se-yeast] with a no-Se control group (0 mg of Se/wk). Treatment groups were balanced for healthy and footrot-affected ewes. For 1 yr, ewes were individually dosed once weekly with 0, 4.9, 14.7, or 24.5 mg of Se, quantities equivalent to their summed daily supplementation rates. Serum- and WB-Se concentrations were measured every 3 mo in all ewes; additionally, WB-Se concentrations were measured once monthly in one-half of the ewes receiving 0 or 4.9 mg of Se/wk. Ewes receiving no Se showed a 78.8 and 58.8% decrease (P < 0.001) in WB- (250 to 53 ng/mL) and serum- (97 to 40 ng/mL) Se concentrations, respectively, over the duration of the study. Whole-blood Se decreased primarily during pregnancy (-57%; 258 to 111 ng/mL) and again during peak lactation (-44%; 109 to 61 ng/mL; P < 0.001). At 4.9 mg of Se/wk, Se-yeast (364 ng/mL, final Se concentration) was more effective than Na-selenite (269 ng/mL) at increasing WB-Se concentrations (P < 0.001). Supranutritional Se-yeast dosages increased WB-Se concentrations in a dose-dependent manner (563 ng/mL, 14.7 mg of Se/wk; 748 ng/mL, 24.5 mg of Se/wk; P < 0.001), whereas WB-Se concentrations were not different for the Na-selenite groups (350 ng/mL, 14.7 mg of Se/wk; 363 ng/mL, 24.5 mg of Se/wk) or the 4.9 mg of Se/wk Se-yeast group (364 ng/mL). In summary, the dose range whereby Se supplementation increased blood Se concentrations was more limited for inorganic Na-selenite than for organic Se-yeast. The smallest rate (FDA-recommended quantity) of organic Se supplementation was equally effective as supranutritional rates of Na-selenite supplementation in increasing WB-Se concentrations, demonstrating the greater oral bioavailability of organic Se.