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Effects of dietary vitamin E, selenium, and polyunsaturated fats on in vivo lipid peroxidation in the rat as measured by pentane production.

Starting at 21 days of age, groups of six rats each were fed a basal Torula yeast diet supplemented with 0.4% L-methionine and varying amounts of vitamin E as dl-alpha tocopherol acetate, selenium as sodium selenite, and with either 10% stripped corn oil, stripped lard, or coconut oil. By 7 wk, pentane production by rats fed a corn oil diet deficient in both vitamin E and selenium was twice that by rats fed 0.1 or 1 mg of selenium per kg of the same basal diet. Blood glutathione peroxidase activity after 7 wk was proportional to the logarithm of dietary selenium. Groups of rats fed the vitamin E- and selenium-deficient diets with lard or coconut oil had one-half the pentane production of rats fed the vitamin E- and selenium-deficient corn oil diets. The plasma level of linoleic plus arachidonic acid was 1.8 time greater on a wt % basis in rats fed corn oil than in rats fed lard or coconut oil as the fat source. Pentane production by rats fed 40 i.u. dl-alpha tocopherol acetate per kg of the selenium-deficient corn oil diet was one-sixth of that by rats fed the same diet without vitamin E; the plasma of the rats fed the vitamin E-supplemented corn oil diet had a level of vitamin E that was about six times greater than that of the rats fed the vitamin E-deficient corn oil diet.

Animals↗

Levels of selenium in plasma and glutathione peroxidase in erythrocytes and the risk of breast cancer. A case-control study.

Plasma selenium and glutathione peroxidase in erythrocytes were analyzed in a case-control study encompassing 441 cases with breast cancer and 191 controls with benign breast disease. No difference in mean serum selenium level between cases and controls on supplementary selenium intake was seen. If only individuals without supplementary intake, 278 cases and 135 controls, were considered a preventive effect was found increasing with selenium level. This finding was significant among women 50 years old or more with Mantel-Haenszel odds ratio = 0.16 for individuals with serum selenium > 1.21 mumol/L. Also for subjects with serum selenium in the range 1.00-1.21 mumol/L a significant preventive effect was seen with odds ratio = 0.38. For women under 50 years of age a nonsignificant preventive effect was seen. Glutathione peroxidase in erythrocytes did not correlate well with serum selenium and was not a marker for the risk of breast cancer.

Aged↗

Selenium status in Charadriiformes. Tissue distribution and seasonal, geographical, and species variation.

The distribution of selenium in a marine wader, the Oystercatcher (Haematopus ostralegus) is given by the levels in 15 tissues and plasma. Red blood cells (RBC) contain the highest level (23 mg/kg dry wt) followed by liver, lung, and kidney (17-19 mg/kg). Most other tissues range from 3-10 mg/kg. The average kidney and liver concentrations of the Oystercatcher belong to the concentrations characteristic in birds. However, the Oystercatcher's tissue selenium concentrations are in general four- to fivefold mammalian levels, but in liver and lung, 11- to 13-fold and in the RBC, 12- to 33-fold. The selenium plasma and RBC levels of the Oystercatcher vary during the year from 280 to 410 micrograms/L and 13 to 30 mg/kg dry wt, respectively; the plasma concentrations are positively correlated with the RBC selenium concentrations. An overview of literature data shows that the selenium kidney and liver concentrations of birds do not vary with geographical latitude and size (length) of the birds. In species of the orders Charadriiformes and Procellariiformes, high selenium kidney, and to a lesser extent liver, concentrations may occur. A function of selenium in antioxidation is suggested.

Animals↗

Determination of selenium in the human brain by graphite furnace atomic absorption spectrometry.

For the investigation of neurological disorders, a development of simple and accessible methods for determining selenium in human brain samples is required. We devised a method of determining selenium using graphite furnace atomic absorption spectrometry (GFAAS). An electrodeless discharge lamp provided the sufficient sensitivity to determine brain selenium. The matrix interferences were avoided by using high temperature, a prolonged pyrolysis step, and a palladium matrix modifier. The technique of standard addition was used to evaluate the sample concentrations. The accuracy of the method was confirmed by a bovine liver reference material. The detection limit of selenium was 0.04 ng. The determined selenium concentrations of human brain cortex and white matter were higher than those of putamen (115-155 and 206-222 ng/g wet wt, respectively). These GFAAS values agreed with those obtained by fluorometric analysis (r = 0.91, n = 10). Moreover, the GFAAS values were compatible to those reported by other researchers (99-274 ng/g wet wt), in which selenium concentrations in putamen also tended to be higher than the other two regions. We conclude that GFAAS is useful for selenium analysis in brain samples.

Brain↗

Determination of the daily selenium intake in Slovakia.

Three models were used to determine the daily dietary Selenium intake in Slovakia. The Selenium content of food produced and consumed in the Slovak Republic was used to estimate and calculate the daily Selenium intake based on food consumption data per capita and seven days, (24 h) eating protocol models. In a duplicate portion model, Selenium was analyzed in a whole day hospital diet during an eight-day period. According to these models the daily dietary Selenium intake was 38.2 microg; 43.3 +/- 6.5 microg for men and 32.6 /- 6.6 microg for women; 27.1 +/- 7.8 microg for normal and 32.3 +/- 4.8 microg for nourishing hospital diets. The main contributors of Selenium to daily intake were the following: eggs, pork, and poultry. The obtained results indicate that the daily dietary intake of Selenium of the Slovak people is below the recommended values.

Adult↗

The importance of selenium in the prenatal and postnatal development of calves and lambs.

Selenium deficiency is responsible for Zenker type muscle degeneration in calves, lambs, and foals in the prenatal and postnatal stages of development. Investigations have shown that the selenium GSH Px, and vitamin E content of the maternal and fetal parts of the placenta in cattle are different. Similarly, low concentrations of selenium are present in milk from cows and sheep. In addition to an inadequate supply of selenium and vitamin E as a contributory cause of fetal nutritive muscular dystrophy (FNMD), it is assumed that a placental transport block and/or impaired selenium metabolism in the placenta are also responsible. Postnatal nutritive muscular dystrophy, however, is attributed to either acute selenium and vitamin E deficiency in basic feed or impaired plant absorption of selenium as a result of antagonistic elements, such as sulphur.

Animals↗

Synergistic toxicity between arsenic and methylated selenium compounds.

Arsenite has been known for half a century to have a protective effect against selenium poisoning. Paradoxically, arsenite inhibits the conversion of inorganic selenium salts to methylated excretory products, although methylation has long been regarded as a detoxification mechanism for selenium. Moreover, there is evidence for a pronounced synergistic toxicity between arsenite and methylated selenium metabolites. We investigated the effect of arsenite on the acute toxicity of a variety of methylated or nonmethylated selenium compounds, as well as methylated forms of sulfur and tellurium. Adult male rats were injected with sodium arsenite (4 mg As/kg bw, s.c.) 10 min prior to injection of the test compounds; at the doses employed, none of the test compounds caused mortality, nor did arsenite, when given alone. When given with arsenite, the following methylated compounds produced toxic signs and high morality at the indicated dosages (mg Se/kg): Methylseleninic acid (2), dimethylselenoxide (2), trimethylselenonium chloride (3), selenobetaine (2), selenobetaine methylester (2, also 1 and 0.5), and Se-methylselenocysteine (2). Toxic signs but not mortality occurred when arsenite was given with selenomethionine (2 mg Se/kg). No enhancement of toxic signs or mortality occurred when arsenite was given with sulfobetaine (0.8 mg S/kg), dimethylsulfide (320 mg S/kg), or the following (nonmethylated) forms of selenium: sodium selenite (2), selenocystine (2), and phenylselenol (2). Arsenite also increased the toxicity of trimethyltelluronium chloride (4.8 mg Te/kg). Like arsenite, periodate-oxidized adenosine (100 mumoles/kg), which is known to inhibit the formation of dimethylselenide and trimethylselenonium ion in vivo, caused increased 24 h mortality when given with various methylated selenium compounds.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Selenium in platelets.

Blood and its main components are commonly used to detect states of selenium deficiency. In order to examine whether human platelets are able to provide better or additional information, improvements of the analytical method resulted in surprisingly narrow normal ranges for selenium and other mineral elements using neutron activation analysis (NAA) and atomic absorption spectrophotometry (AAS), and controlling thermal neutron flux, (n, gamma)-cross sections, mean platelet wet wt, and water fraction of the platelets. Previously reported selenium concentrations in platelets on wet wt basis in the order of 500 ng/g--half of which had been found to derived from early bone marrow precursors using 74Se-selenite--were reproduced by NAA and AAS. However, with the new analytical method the selenium concentrations showed a narrower normal range than that of plasma. Moreover, platelet selenium did not in all cases correlate with plasma selenium. Cellular tissues such as platelets should, therefore, help to detect latent states of selenium deficiency.

Adult↗

Selenium reduces high energy shock wave-induced renal injury in rats.

Using an in vitro model with Madin-Darby canine kidney (MDCK) cells, we showed that shock wave-induced renal injury could be ameliorated by selenium. We examined the influence of selenium, a free radical scavenger, in shock wave-induced tubular cell injury in vivo. Male rats were randomly assigned to three groups: 1 control (n= 18), 2 selenium (n = 18), 3 sham treatment (n = 4). Groups 1 and 2 were treated with 500 shock waves on each kidney. Animals assigned to group 3 (sham treatment) received only anesthetics. Selenium (80 microg/kg per 24 h intraperitoneally) was given to the animals in group 2 for 5 days, starting 1 day before shock wave exposure. Urine was collected for 8 h on the day before and immediately, 1, 7 and 28 days after shock wave exposure (SWE) for the measurement of urine volume, N-acetyl-beta-glucosaminidase (NAG), beta-2-microglobulin (beta2 M), and creatinine. Blood was taken from these rats on day 1 after SWE for the determination of creatinine and the calculation of the creatinine clearance (CCr). After SWE, there was a significantly increased diuresis in group 1 and 2. The excretion of NAG and beta2 M was also increased in both groups. These changes were significantly less pronounced in the selenium treated rats. CCr was higher in the selenium group than in the controls. No changes were observed in the sham treated group. These results demonstrate that selenium is able to ameliorate the damaging effects of high energy shock waves on renal tissue not only in vitro, but also in vivo.

Animals↗

Selenium and mercury concentrations in brood-stock walleye collected from three sites on Lake Oahe.

A decline in the walleye Stizostedion vitreum sport fishery in lower Lake Oahe, South Dakota, was documented in the early 1980s and has been attributed to poor natural reproduction and/or recruitment. Contaminants were suspected of causing low natural reproduction/recruitment in lower Lake Oahe as well as low hatchability of eggs produced from broodstock walleyes taken from lower Lake Oahe. Concentrations of dissolved selenium in the Cheyenne River, which enters lower Lake Oahe, have increased considerably over the last 15 years. To determine whether selenium concentrations contributed to the reproduction problems in the lower Lake Oahe walleye population, adult walleye were collected during spawning operations in April 1994, 1995, and 1996 to obtain tissue samples. Muscle, liver, reproductive tissue, and unfertilized eggs were analyzed with a modified fluorometric method for determining selenium concentrations in plants. These tissues were also analyzed for mercury content using cold-vapor atomic absorption. No statistical differences (p < 0.05) in selenium or mercury concentrations among sites could be determined that would explain differential walleye egg hatchability. Correlation analysis determined significant inverse associations existed between the gonadal somatic index of male walleye and gonadal tissue selenium concentrations (r = -0.41, p = 0.0012). Both walleye sexes exhibited significant inverse associations between the hepatic somatic index (HSI) and liver selenium concentrations (males r = -0.33, p = 0.0095; and females r = -0.38, p = 0.0034). Positive relationships existed for female walleye selenium concentrations in the liver and the ovaries (r = 0.37, p = 0.003) and the liver and muscle tissue (r = 0.28, p = 0.027). Mercury concentrations in walleye ovaries were positively correlated with HSI (r = 0.30, p = 0.0012), length (r = 0.36, p = 0.0046), relative weight (r = 0.36, p = 0.0054), and muscle concentrations (r = 0.49, p = 0.0001). Mercury concentrations in male walleye muscle were correlated with age (r = 0.57, p = 0.0001), length (r = 0.79, p = 0.0001), and mercury concentrations in the testes (r = 0.43, p = 0.0006).

Animals↗

Normal values for arsenic and selenium concentrations in human lung tissue.

Normal values and ranges were determined for arsenic and selenium concentrations in lung and hilus tissue. The study group consisted of 50 deceased persons, who were examined by autopsy at the Institute for Pathology of the University of Erlangen-Nuremberg. Taking into consideration topographic-anatomical criteria, samples were taken of each lung lobe and the hilar lymph nodes. The dried tissue was analyzed using by means of hydride atomic absorption spectrometry after wet-oxidative digestion. Normal values ranged for the arsenic concentrations from <1-74 ng/g dry weight and for the selenium concentrations from <3-574 ng/g dry weight. Arsenic was found to accumulate in the hilus tissue, whereas selenium did not. Considerable intraindividual and interindividual variation was found for both arsenic and selenium. There were no statistically significant differences regarding age, smoking habits, and lung diseases. Lung tissue samples from three deceased persons from Houston, Texas, contained lower arsenic concentrations and somewhat higher levels of selenium compared to the German autopsies; these levels were, however, still within the indicated normal ranges. The following conclusions can be drawn from the results available at present: Intraindividual and interindividual variation is high for the arsenic and selenium concentrations in human lung tissue, so that only relatively wide normal ranges can be given for the general population. Smoking habits, age, and lung diseases do not seem to affect the indicated normal ranges. Postmortem determination of arsenic and selenium concentrations in human lung tissue can provide important information on former occupational or environmental exposure.

Adult↗

The impact of cardiopulmonary bypass on selenium status, thyroid function, and oxidative defense in children.

Selenium has important functions for oxidative defense and thyroid hormone metabolism. Selenium-dependent enzymes include 5'-iodothyronine deiodinase and glutathione peroxidase (GPX). The objective of this study was to investigate the relationship between plasma selenium, GPX activity, and thyroid hormone status in pediatric cardiac surgical patients. Plasma concentrations of selenium, free triiodothyronine (fT3), free thyroxin (fT4), and c-reactive protein as well as plasma activity of GPX were prospectively evaluated at anesthetic induction and 48 hours postoperatively in 59 children requiring cardiopulmonary bypass (CPB). GPX was measured at additional time points at 6, 12, and 24 hours postoperatively. There was a significant reduction in the plasma selenium concentration after cardiopulmonary bypass with obtained median measurements of 0.61 micromol/L (induction) and 0.51 micromol/L (48 hours postoperatively). The fT3/fT4 ratio decreased significantly from 0.28 at anesthetic induction to 0.22 at 48 hours postoperatively. There were no significant changes of GPX activity. 48 hours fT3 concentration, fT3/fT4 ratio, and selenium concentration were significantly negatively correlated with the time spent in intensive care. The concentration of plasma selenium in children undergoing cardiopulmonary bypass significantly decreases, resulting in diminished deiodinase activity, and a subsequent reduction in the conversion of T4 to T3.

Adolescent↗

Serum selenium measurements in women with early-stage breast cancer with and without chemotherapy-induced ovarian failure.

Blood selenium has been shown to decline as breast cancer progresses and fluctuate with estrogen. The objective of this study was to determine the effect of estrogen depletion resulting from chemotherapy-induced ovarian failure on serum selenium and selenoproteins in stage I/II premenopausal breast cancer patients. Serum selenium, glutathione peroxidase (GPx) activity, and selenoprotein P (SelP) were measured and a dietary questionnaire was completed at baseline (before chemotherapy) and 6, 12, and 24 months after start of chemotherapy. Twelve months after the start of adjuvant chemotherapy 33 (75%) patients developed ovarian failure (OF) and 11 (25%) retained menstrual function (non-OF). Dietary selenium intake was 30-58% above the Recommended Dietary Allowance for both groups. By six months the mean estradiol (pg/ml) was lower in the OF group than in the non-OF group (32+/-5 versus 140+/-62 pg/ml, p=0.01) and this difference was maintained at 12 and 24 months. However, there was no differences in serum selenium, GPx activity, or SelP in the OF and non-OF groups at 6, 12, and 24 months. Selenium status in premenopausal breast cancer patients, as measured by serum selenium, GPx and SelP, was within the normal range before and following adjuvant chemotherapy, and was not affected by chemotherapy-induced ovarian failure.

Administration, Oral↗

Selenium and antioxidant defenses as major mediators in the development of chronic heart failure.

Increased oxidative stress is involved in the pathogenesis of chronic heart failure (CHF), the common end result of most cardiac diseases. Selenium is an "essential" trace element, which means that it must be supplied by our daily diet and that its blood and tissue concentrations are extremely low. Selenium has a variety of functions. It is a key component of several functional selenoproteins required for normal health. The best known of these are the antioxidant glutathione peroxidase (GPx) enzymes, which remove hydrogen peroxide and the harmful lipid hydroperoxides generated in vivo by oxygen-derived species. GPx deficiency exacerbates endothelial dysfunction, a major contributing factor in the severity of CHF symptoms, in various conditions such as hyperhomocysteinemia. This suggests that homocysteine may be involved in the CHF associated endothelial dysfunction through a peroxide-dependent oxidative mechanism. Selenium also plays a role in the control of thyroid hormone metabolism and in protection against organic and inorganic mercury. One possible additional mechanism by which low selenium may compromise cardiovascular condition may be through the effect of selenium on the synthesis and activity of deiodinases, enzymes converting thyroxin into the biologically active triiodothyronine. Selenium and iodine actually interact in cardiovascular physiology, and further studies are needed to examine their role, in isolation and in association, in the development of CHF. Thus, selenium (through its role in selenoenzymes, thyroid hormones, and interactions with homocysteine and endothelial function) appears to be a major mediator in several pathways potentially contributing to CHF development.

Antioxidants↗

Effects of dietary selenium on post-ischemic expression of antioxidant mRNA.

Cardiac ischemia reperfusion leads to oxidative stress and poor physiological recovery. Selenium deficiency down-regulates thioredoxin reductase (Txnrd) and glutathione peroxidase (Gpx) activity, impairing recovery from ischemia-reperfusion. Furthermore, selenium supplementation has been shown to be cardioprotective and lessens oxidative stress in reperfused rat hearts. In this study we have investigated the role of selenium in the mRNA expression of these, and related antioxidant proteins, post ischemia-reperfusion. Male rats were fed varying doses of selenium for five weeks. Hearts were isolated and perfused using the Langendorff method with 22.5 min of global ischemia and 45 min reperfusion. RNA was extracted for quantitative real-time PCR analysis of glutathione peroxidase (Gpx)-1 and 4, glutathione reductase (Gsr), thioredoxin peroxidase-2 (Prdx2), thioredoxin (Txn) and thioredoxin reductase (Txnrd)-1 and 2 gene expression. Selenium deficiency produced significant reductions in Gpx-1, Gpx-4, Prdx2, Txnrd-1 and Txnrd-2 expression. Conversely, selenium supplementation of 1000 microg/kg significantly up-regulated Gpx-1, Gpx-4, Txn, Txnrd-1 and Txnrd-2 transcription. Our results show selenium modulates the cardiac mRNA expression of thioredoxin and glutathione related enzymes post ischemia-reperfusion, and impacts on tolerance to ischemia-reperfusion.

Animal Nutritional Physiological Phenomena↗

Effects of selenium supplement on the de novo biosynthesis of glycerolipids in the isolated rat heart.

The effect of selenium supplement on glycerolipid biosynthesis in the isolated rat heart was investigated. Selenium was administered to the rat by intraperitoneal injection of 4.33 mumol/kg per day for 3 consecutive days. Animals administered with an equal volume of saline were used as controls. Hearts from both animal groups were perfused in Krebs-Henseleit buffer containing labelled glycerol. Subsequent to perfusion, the radioactivity associated with each glycerolipid group was determined. Selenium supplement caused elevations in the labelling of phosphatidic acid and phosphatidylcholine but not in other phospholipids, diacylglycerol or triacylglycerol. The mechanisms for the enhancement of labelling into phosphatidic acid and phosphatidylcholine were examined. The activity of the enzymes responsible for the synthesis of phosphatidic acid in the rat heart was not changed by selenium supplement. However, a 51% increase in the acyl-CoA level was detected which might account for the elevated labelling of phosphatidic acid in the selenium supplemented animal. The 2-fold increase in the activity of CDPcholine:diacylglycerol cholinephosphotransferase might also account for the increase in the labelling of phosphatidylcholine in the heart of the selenium-supplemented rat. It is clear from this study that selenium plays a regulatory role in the control of cellular lipid metabolism.

Animals↗

Interaction of adriamycin aglycones with isolated mitochondria. Effect of selenium deficiency.

Adriamycin (AdM) aglycones have dramatic effects on isolated heart mitochondria, oxidizing pyridine nucleotides, modifying sulfhydryl groups, and triggering a permeability transition of the inner membrane that results in free passage of solutes smaller than 1500 Da. In this investigation, the role of glutathione (GSH) peroxidase in these actions of the aglycones was evaluated, by comparing mitochondria from selenium-deficient and selenium-supplemented rats, with the following results. Selenium deficiency was without effect on the permeability transition of heart mitochondria, followed via Ca2+ release and triggered by AdM aglycone or by t-butyl hydroperoxide (TBH) or H2O2, both of which are authentic substrates of the peroxidase. The permeability transition of liver mitochondria was delayed by selenium deficiency regardless of the triggering agent; however, substantial triggering by the aglycone and TBH persisted in mitochondria from selenium-deficient animals. Selenium deficiency inhibited thiol modification elicited by AdM aglycone and H2O2 in heart mitochondria and by the aglycone, TBH, and possibly H2O2 in liver mitochondria. It would thus appear that AdM aglycone, TBH, and H2O2 can induce the permeability transition of isolated heart mitochondria via a process (or processes) distinct from the catalytic activity of the peroxidase. Furthermore, even in liver, where involvement of the peroxidase is observed, mechanisms other than the GSH cycle can contribute to transition induction by the aglycone and by TBH. Finally, mitochondrial-SH group modification by the aglycones appeared not to be causally linked to induction of the permeability transition. This laboratory has suggested that the effects of aglycone metabolites of AdM on mitochondria mediate the cardiotoxicity that limits use of the parent drug. The data presented in this paper argue against the involvement of GSH peroxidase in that process. They are in agreement with in vivo studies, which have generally failed to find evidence for amelioration of AdM cardiotoxicity in selenium-deficient animals.

Animals↗

Serum selenium concentration and disease progress in patients with HIV infection.

The selenium concentration in the serum of 67 patients with HIV infection was measured to determine whether selenium deficiency occurred in the different stages of the disease. In the first stage of the study, patients were divided into four groups: symptom-free subjects, PGL (persistent generalized lymphadenopathy), ARC (AIDS related complex), and AIDS (acquired immunodeficiency syndrome). Selenium concentrations were normal in HIV antibody positive symptom-free subjects (1.18 +/- 0.27 mumol/L) and lower than normal in the other three groups (p less than 0.001). There was a significant correlation (p less than 0.001) between selenium levels and values of hemoglobin and erythrocyte sedimentation rate. Selenium deficiency was in no case associated with a lack of zinc in serum (also determined in all patients). In the second stage of the study, 12 patients were treated for a period of two months with low doses of selenium to assess whether such supplementation was able to restore their impaired immunological and hematological functions. The therapy increased serum selenium concentrations (from 0.77 +/- 0.23 to 1.44 +/- 0.41 mumol/L) and symptomatic improvements were noted. However, no changes were observed in the immunological and hematological parameters.

Adult↗