Efficacy of dietary selenium sources on growth and carcass characteristics of growing-finishing pigs fed diets containing high endogenous selenium.

A study was conducted to determine the efficacy of organic (Se-yeast, SelenoSource AF, Diamond V Mills Inc., Cedar Rapids, IA) and inorganic sources of Se on growth performance, tissue Se accretion, and carcass characteristics of growing-finishing pigs fed diets with high endogenous Se content. A total of 180 pigs at 34.4 +/- 0.06 kg of BW were allotted to 1 of 5 dietary treatments: a negative control without added Se (NC); 3 treatment diets with 0.1, 0.2, or 0.3 mg/kg of added Se from an organic source; and a diet with 0.3 mg/kg of added Se as sodium selenite. Each treatment had 6 pens, with 6 pigs per pen-replicate. Experimental diets were changed twice at 66.1 +/- 0.5 kg and 99.0 +/- 0.9 kg of BW, and were fed until the pigs reached market weight. Growth performance was measured at the end of each phase. Upon reaching 129.9 +/- 1.4 kg of BW, the pigs were transported to a local abattoir (Seaboard Foods, Guymon, OK), where carcass, loin, and liver samples were obtained. Hair and blood samples were obtained at the beginning and end of the study for Se analysis. Growth performance did not differ (P > 0.05) among treatments. Percent drip loss of the NC pigs was greater (2.41 vs. 1.75, P = 0.011) compared with pigs supplemented with Se. Pigs fed diets with added Se had greater Se concentrations in the liver (0.397 vs. 0.323 ppm, P = 0.015), loin (0.236 vs. 0.132 ppm, P < 0.001), serum (0.087 vs. 0.062 ppm, P = 0.047), and hair (0.377 vs. 0.247 ppm, P = 0.003) compared with the NC pigs. Percentage drip loss was linearly reduced [percent drip loss = 2.305 - (2.398 x Se), r2 = 0.29, P = 0.007] as dietary organic Se concentration increased. The Se concentration (ppm) in the liver [liver Se = 0.323 + (0.291 x Se), r2 = 0.33, P = 0.003], loin [loin Se = 0.122 + (0.511 x Se), r2 = 0.57, P < 0.001], serum [serum Se = 0.060 + (0.113 x Se), r2 = 0.33, P = 0.004] and hair [hair Se = 0.237 + (0.638 x Se), r2 = 0.56, P < 0.001] increased linearly as dietary organic Se concentration increased. Slope ratio analysis indicated that the relative bioavailability of organic Se for percent drip loss and loin and hair Se response was 306, 192, and 197% of that for inorganic Se, respectively. The results of the study show a potential advantage of organic Se supplementation in reducing drip loss even when the basal diet contains an endogenously high Se concentration of 0.181 ppm.

Dimethyldiselenide and methylseleninic acid generate superoxide in an in vitro chemiluminescence assay in the presence of glutathione: implications for the anticarcinogenic activity of L-selenomethionine and L-Se-methylselenocysteine.

The reduction of cancer incidence by dietary supplementation with L-selenomethionine, L-Se-methylselenocysteine, and other methylated selenium compounds and metabolites is believed to be due to the metabolic generation of the monomethylated selenium species methylselenol. Dimethyldiselenide and methylseleninic acid were reduced by glutathione in an in vitro chemiluminescent assay in the presence of lucigenin for the detection of superoxide (O2-.). The methylselenol produced on reduction of dimethyldiselenide and methylseleninic acid was found to be highly catalytic, continuously generating a steady state of O2-. The O2-. detected by the chemiluminescence generated by methylselenol was fully quenched by superoxide dismutase, causing a complete cessation of chemiluminescence. In contrast, dimethyldisulfide in the presence of glutathione was not catalytic to any measurable extent and did not generate any superoxide. These in vitro results suggest that methylselenol catalysis is possible in vivo, and if metabolism generates sufficient concentrations of methlylselenol from L-selenomethionine or L-Se-methylselenocysteine in vivo, it could change the redox status of cells and oxidatively induce cellular apoptosis.

Effect of dietary copper on selenium toxicity in Fischer 344 rats.

The purpose of this study was to investigate the ameliorating effects of dietary copper supplementation on selenium toxicity. Nine groups (n = 6) of weanling Fischer 344 female rats were randomly assigned to treatment groups and fed diets containing nontoxic levels of copper as CuCl2 and/or selenium as selenite or selenocystamine. Weight gain, liver and spleen weights, plasma lipid peroxidation, and liver selenium and copper content were analyzed after the 6-wk treatment period. Concentrations of up to 10 times the daily lethal dose of dietary selenium were well tolerated in rats supplemented with dietary copper. As the dietary level of selenium was increased, the ratio of selenium to copper measured in the liver decreased. In the groups of rats in which dietary copper supplementation was absent and dietary selenium was supplemented, copper stores in the liver remained unchanged from control values. Copper's protective effects from dietary selenium toxicity may come from the formation of a copper-selenide complex that renders both selenium and copper metabolically unavailable and nontoxic.

Selenium compounds have disparate abilities to impose oxidative stress and induce apoptosis.

The cancer chemopreventive effect of selenium cannot be fully accounted for by the role of selenium as a component of the antioxidant enzyme glutathione peroxidase, which suggests that chemoprevention occurs by another mechanism. Several studies have shown that thiol oxidation and free radical generation occur as a consequence of selenium catalysis and toxicity. In the present study, we evaluated three different selenium compounds; selenite, selenocystamine, and selenomethionine to determine the relative importance of the prooxidative effects of these compounds with regard to their ability to induce apoptosis. The experimental results suggest that, in addition to supporting an increased activity of glutathione peroxidase, an antioxidant function that the three selenium compounds did with equal efficacy, catalytic selenite, and selenocystamine generated 8-hydroxydeoxyguanosine DNA adducts, induced apoptosis and were found to be cytotoxic in mouse keratinocytes. The noncatalytic selenomethionine was not cytotoxic, did not generate 8-hydroxydeoxyguanosine adducts and did not induce cellular apoptosis at any of the selenium concentrations studied. In keratinocytes, apoptosis may be initiated by superoxide (O2*-) and oxidative free radicals that are generated by selenite and selenocystamine, but not by selenomethionine.

Bioavailability of selenium from veal, chicken, beef, pork, lamb, flounder, tuna, selenomethionine, and sodium selenite assessed in selenium-deficient rats.

The bioavailability of selenium (Se) from veal, chicken, beef, pork, lamb, flounder, tuna, selenomethionine (SeMet), and sodium selenite was assessed in Se-deficient Fischer-344 rats. Se as veal, chicken, beef, pork, lamb, flounder, tuna, SeMet, and sodium selenite was added to torula yeast (TY) basal diets to comprise Se-inadequate (0.05 mg Se/kg) diets. Se as sodium selenite was added to a TY basal diet to comprise a Se-adequate (0.10 mg Se/kg), Se-control diet. The experimental diets were fed to weanling Fischer-344 rats that had been subjected to dietary Se depletion for 6 wk. After 9 wk of the dietary Se repletion, relative activity of liver glutathione peroxidase (GSHPx) from the different dietary groups compared with control rats (100%) was: flounder 106%, tuna 101%, pork 86%, sodium selenite 81%, SeMet 80%, beef 80%, chicken 77%, veal 77%, and lamb 58%. Se from flounder was the most efficient at restoring Se concentrations in the liver and skeletal muscle. Se from sodium selenite, SeMet, beef, veal, chicken, pork, lamb, and tuna was not dietarily sufficient to restore liver and muscle Se after 9 wk of recovery following a 6-wk period of Se depletion.

Inhibition of selenite-catalyzed superoxide generation and formation of elemental selenium (Se(o)) by copper, zinc, and aurintricarboxylic acid (ATA).

Selenite catalyzes the oxidation of glutathione (GSH) with the subsequent generation of superoxide (O2.-). Copper, zinc, and aurintricarboxylic acid (ATA) were tested for their ability to inhibit both the selenite-catalyzed generation of superoxide and the conversion of selenite to elemental selenium (Se(o)). As measured by lucigenin-dependent chemiluminescence (CL), copper, zinc, and ATA were shown to inhibit significantly (P < 0.05) selenite-catalyzed CL in a concentration-dependent manner. The inhibition of the selenium-catalyzed generation of superoxide by copper(II) was greater than by either zinc or ATA. In addition, Copper, zinc, and ATA all inhibited the conversion of selenite to Se(o). Inhibition of selenite-catalyzed CL by copper, zinc, and ATA is believed to occur as the result of inhibition of Se2- and/or GSSe-, the catalytic selenopersulfide anion of GSH.

Selenium from beef is highly bioavailable as assessed by liver glutathione peroxidase (EC 1.11.1.9) activity and tissue selenium.

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.

On the nature of selenium toxicity and carcinostatic activity.

Selenium toxicity was first confirmed in 1933 to occur in livestock that consumed plants of the genus Astragalus, Xylorrhiza, Oonopsis, and Stanleya in the western regions of the United States. In 1957 selenium was identified as an essential nutrient for laboratory rats and soon thereafter for chickens and sheep. Essentiality for mammalian species was established in 1973 with the discovery that the enzyme glutathione peroxidase contained selenium. During this same period of time, human epidemiological evidence suggested that selenium possessed anticarcinogenic effects. Since the 1970s, many animal studies have confirmed the human epidemiologic evidence that selenium compounds possess carcinostatic activity. Less progress has been made in explaining why many of these compounds of selenium are toxic and why these same compounds are carcinostatic. In 1988 the observation was made that oxidation of glutathione by selenite produced superoxide, opening a new area for selenium research. This present paper, drawing information from the literature on selenium metabolism in plants and animals, selenium toxicology, selenium cytotoxicity, and selenium carcinostatic activity in animals over the last sixty years, sets forth a probable biochemical catalytic mechanism that encompasses both selenium toxicity and selenium carcinostatic activity. The thesis presented here for scrutiny is that compounds of selenium are toxic owing to their prooxidant catalytic activity to produce superoxide (O2.-), hydrogen peroxide, and very likely other cascading oxyradicals. The toxicity of selenium compounds is countered by plant and animal methylation reactions and antioxidant defenses. As carcinostasis is mostly known to occur at supranutritional levels of selenium in animals, carcinostasis appears to be directly correlated to selenium toxicity. The catalytic toxic selenium specie appears to be the metabolic selenide (RSe-) anion.

Bioavailability of selenium from raw and cooked ground beef assessed in selenium-deficient Fischer rats.

OBJECTIVE: The literature on the bioavailability of selenium (Se) from meats, especially beef, is meager, and that which existed when this research began suggested that Se was not highly bioavailable. In addition, much of the analytical values for Se in beef predated the Food and Drug Administration's 1973 approval of Se as an additive to feeds and mineral premixes of livestock. DESIGN: One hundred and thirty-six weanling female Fischer 344 rats were divided into two dietary groups: the selenium deficient group in which animals were fed a torula yeast (TY) basal diet which contained 0.008 mg/kg Se and the control group in which animals were fed the TY diet to which was added 0.10 mg/kg Se as sodium selenite. RESULTS: After 6 weeks of dietary treatment liver glutathione peroxidase (GSHPx) activity had fallen in the Se-deficient rats to 2.4% of that of control rats. At this time (week 6) rats from the Se-deficient TY diet were refed diets containing 0.10 mg/kg Se as selenite, selenate, raw or cooked ground beef that had been freeze-dried. During the Se-repletion period rats were sacrificed at weeks 1, 3, 5 and 8. Liver GSHPx activity and total Se levels in liver and muscle tissue were the criteria of Se bioavailability. After 8 weeks of Se resupplementation the recovery of liver GSHPx activity compared to the control animals (set at 100%) were selenite (98%, p > 0.05), selenate (117%, p < 0.05), raw beef (127%, p < 0.05) and cooked ground beef (139%, p < 0.05). Total Se in both liver and muscle tissue reflected the liver GSHPx activity with the total Se concentration in tissues being highest for cooked beef. CONCLUSION: The data suggest that bioavailability of Se from ground beef is greater than that from either selenite or selenate.

The selenium content of selected meats, seafoods, and vegetables from Lubbock, Texas.

The selenium content of some frequently consumed foods from a commercial beef packer, a road-side vendor, and local stores in Lubbock, Texas was determined and compared to selenium data for the same or similar foods in the United States and from other countries. The comparative content of selenium in foods covered the period of time between 1970 and 1993. Our selenium analyses of foods show that on a fresh weight basis, the selenium content of seafoods > commercial beef > pork > ground beef > chicken. Cooking, air- or freeze-drying increased the selenium content of all foods significantly. When the selenium content of local foods is compared to similar foods in the United States and other countries, with few exceptions, there exists great uniformity in the selenium content in the major food groups, meats, fish, milk, and vegetables. New Zealand, known for its low soil selenium, had the lowest comparative food selenium content.

Generation of reactive oxygen species from the reaction of selenium compounds with thiols and mammary tumor cells.

Sodium selenite, sodium selenate, selenocystine and selenomethionine were tested for their abilities to generate superoxide by the oxidation of glutathione and other thiols in the absence and presence of cells of the human mammary tumor cell line HTB123/DU4475. Free radical generation was measured by lucigenin- or luminol-amplified chemiluminescence. In the absence of tumor cells, lucigenin-dependent chemiluminescence was observed from the reaction of selenite with the thiols glutathione, 2-mercaptoethanol and L-cysteine, but not with oxidized glutathione. Superoxide dismutase, catalase, and glutathione peroxidase all suppressed the observed chemiluminescence; but when these enzymes were heat inactivated they had little suppressive inhibition on chemiluminescence. Luminol-dependent chemiluminescence from the reaction of selenite with glutathione was much less than that observed by lucigenin-amplified chemiluminescence. In the presence of the HTB123/DU4475 mammary tumor cells, lucigenin-dependent chemiluminescence was observed from the reactions of selenite and selenocystine with glutathione which were 5 and 23 times greater than their respective reactions with glutathione in the absence of tumor cells. The enhanced chemiluminescence generated by selenite and selenocystine in the presence of the tumor cells was also suppressed by superoxide dismutase, catalase and glutathione peroxidase. These data suggest that a free radical, the superoxide anion (O2-), and H2O2 are produced from the reaction of selenite and selenocystine with glutathione. These free radical reactions may account for the toxicity of selenite and selenocystine in vitro in comparison to a near absence of acute tumor cell toxicity and superoxide generation by selenate and selenomethionine with thiols. Enhanced chemiluminescence in the presence of tumor cells may be an expression of cellular selenium metabolism and the capability of cells to form selenium metabolites that more easily oxidize glutathione and other thiols producing reactive free radicals and peroxides.

Effect of selenium compounds and thiols on human mammary tumor cells.

The effect on cell viability and growth rate of sodium selenite, selenocystine, sodium selenate, and selenomethionine at selenium concentrations of 6.25 and 12.5 uM was studied in vitro on cells of the human mammary tumor cell line HTB123/DU4475. Selenite and selenocystine affected both cell viability and growth rate of the tumor cells at these selenium concentrations. Selenite and selenocystine decreased intracellular glutathione concentrations, but did not affect tumor cell glutathione peroxidase activity. After six days of exposure to either selenate or selenomethionine, the viability of tumor cells remained stable, but cell growth, as measured by numbers of cells, was retarded. Neither selenate nor selenomethionine produced changes in concentrations of intracellular glutathione. The toxic effect of selenite on tumor cells was enhanced by addition of 0.25 mM glutathione to the growth medium. Preincubation of the tumor cells with 62.5 uM buthionine sulfoximine decreased cellular glutathione to 15% of controls at 24 h and enhanced the toxicity of selenite toward the tumor cells. Glutathione, 2-mercaptoethanol, and L-cysteine were all toxic to the tumor cells in a dose-dependent manner.

Effect of dietary selenium and magnesium on human mammary tumor growth in athymic nude mice.

The effect of dietary selenium (Se) supplementation and low dietary magnesium (Mg) on growth of cells of the human mammary tumor cell line (HTB123/DU4475) and the tissue glutathione (GSH) content in female athymic nude mice was studied. Sixty three- to four-week-old female athymic nude mice were randomly divided into six dietary groups of 10 animals. The mice were fed a modified AIN-76A diet with two levels of Mg (100 and 665 mg/kg) and three levels of Se (0.04, 0.2, and 4.0 mg/kg). At the fourth week of dietary treatment, mice were subcutaneously inoculated with 2.5 x 10(6) viable tumor cells on the dorsal lumbar region and then fed their respective diets for another four weeks. Dietary Se supplementation had no significant effect on tumor growth or tissue GSH content. Low dietary Mg limited both tumor growth and tissue GSH synthesis but raised Mg and GSH levels in tumor tissues. The growth of mice fed the diet containing 100 mg/kg Mg and 4.0 mg/kg Se was significantly retarded. This study demonstrated that neither Se deficiency nor Se supplementation had any effect on mammary tumor growth or tissue GSH content in athymic nude mice. Low dietary Mg did retard tumor growth and inhibited GSH synthesis. Low dietary Mg also resulted in an apparent increase in Se toxicity in these animals.

Dietary selenium and aniline-induced methemoglobinemia in rats.

Depletion of selenium from rats for 8 weeks decreased blood glutathione peroxidase activity to 5.7% of that in selenium-supplemented (0.5 ppm selenium as Na2SeO3) rats. Aniline (60 mg/kg, i.p.) resulted in no significant difference in methemoglobin and blood reduced glutathione (GSH) levels between Se-deficient and Se-supplemented rats. A lowered aniline dose (36 mg/kg, i.p.) also resulted in no difference in methemoglobin levels. The selenium-deficient rat was able to reduce methemoglobin induced by aniline as efficiently as the selenium-sufficient rat.

Hematologic data of selenium-deficient and selenium-supplemented rats.

Effect of dietary selenium as sodium selenite on in vivo hematological parameters of Sprague-Dawley rats was examined over a 7-month period. Dietary selenium did not alter total hemoglobin, hematocrits, erythrocyte counts, or the osmotic fragility pattern of rat blood. Selenium-excessive (1.0 ppm) rats showed slightly lower but not significantly lower methemoglobin levels than selenium-adequate (0.1 ppm) or selenium-deficient rats. Platelet counts tended to be higher in selenium-excessive rats and lower in selenium-deficient rats than in selenium-adequate rats, but the differences were not statistically significant. No clear trends were observed regarding the effect of dietary selenium on total leukocyte and differential leukocyte counts. After 7 months of dietary treatment blood glutathione peroxidase activity in selenium-deficient rats and in selenium-excessive rats was 16.8% and 142.2% of the activity in selenium-adequate rats. The results indicate that long-term selenium deficiency in rats produces no abnormal hematological parameters or any compensated hemolytic anemia in vivo.

In vitro hemolysis of rat erythrocytes by selenium compounds.

Rat erythrocytes were incubated in vitro with various selenium compounds at 37 degrees. Hemolysis occurred with some selenium compounds but not with corresponding sulfur analogues. Selenite induced more rapid loss of intracellular glutathione (GSH) than did selenocystine but was less hemolytic. Cystine caused neither loss of intracellular GSH nor hemolysis. Addition of GSH to the incubation medium enhanced hemolysis by selenite and selenium dioxide but inhibited hemolysis by selenocystine. Inclusion of glucose in the incubation medium also inhibited selenocystine-induced lysis of erythrocytes from both selenium-supplemented rats and selenium-deficient rats. The results suggest a relationship between the oxidation of intracellular GSH and the hemolysis by selenocystine, selenite and selenium dioxide.

Injectable selenium: effect on the primary response of mice (38472).

Sodium selenite administered to mice ip (ca.5 mug Se) enhances the primary immune response to the sheep red blood cell angigen. Enhancement of the primary immune response is greatest when Se is administered prior to or simultaneously with the sheep red blood cell antigen.