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PubMed1992

The involvement of selenium in peroxisome proliferation caused by dietary administration of clofibrate to rats.

The effects of dietary treatment with clofibrate (0.5% w/w for 10 days) on the livers of selenium-deficient male rats were examined. The peroxisome proliferation (as determined by electron microscopy) in the livers of selenium-deficient animals was much less pronounced than in the case of selenium-adequate rats and no increase in peroxisomal fatty acid beta-oxidation (assayed both as antimycin-insensitive palmitoyl-CoA oxidation and lauroyl-CoA oxidase activity) was observed in the deficient animals. On the other hand, in selenium-deficient rats clofibrate caused increases in the specific activity of microsomal lauric acid omega- and omega-1-hydroxylation and an apparent change in mitochondrial size, seen as a redistribution of mitochondria from the 600 x g(av) pellet to the 10,000 x g(av) pellet, which were approximately 50% as great as the corresponding effects on control animals. Obviously, then, these three different effects of clofibrate are not strictly coupled and may involve at least partially distinct underlying mechanisms. Initial experiments demonstrated that peroxisome proliferation could be obtained by exposing primary hepatocyte cultures derived from selenium-deficient rats to clofibric acid (an in vivo hydrolysis product of clofibrate which is the proximate peroxisome proliferator), nafenopin or mono(2-ethylhexyl)phthalate. This finding suggests that selenium deficiency does not have a direct influence on the basic process(es) underlying peroxisome proliferation, but rather has indirect effects, influencing, for example, the pharmacokinetics of clofibrate and/or hormonal factors.

Animals↗
PubMed1994

Selenium in the maintenance and therapy of HIV-infected patients.

Due to its antiviral effects and its importance for all immunological functions, the administration of selenium is suggested as a supportive measure in early as well as in advanced stages of HIV-induced disease. Initial observations on the effects of selenium supplementation in HIV-infected patients indicate that selenium causes symptomatic improvements and possibly slows the course of the disease. As selenium inhibits reverse transcriptase activity in RNA-virus-infected animals, supplemental selenium could also prevent the replication of HIV and retard the development of AIDS in newly HIV-infected subjects. An adequate supply of selenium and of antioxidant vitamins is also proposed as a measure to reduce the probability of the placental transmission of HIV in pregnancy.

AIDS-Related Complex↗
PubMed1983

Selenium, zinc and copper in Down's syndrome (trisomy 21): blood levels and relations with glutathione peroxidase and superoxide dismutase.

Increased superoxide dismutase and glutathione peroxidase activities have been reported in erythrocytes of subjects with Down's syndrome. Since these enzymes contain specific trace-elements as essential components, we have determined copper, zinc and selenium levels in plasma and erythrocytes of 29 trisomy 21 patients compared with 32 age-matched controls and examined the relations with the enzymes' activities. In plasma, mean zinc and copper levels were normal, but selenium was found to be significantly decreased (p less than 0.001). In red cells, the increase of activity of the selenoenzyme glutathione peroxidase (p less than 0.001) was not accompanied by an increase of erythrocyte selenium, but a significant correlation was found between these two values (r = 0.67, p less than 0.001). Zinc and copper levels in red cells were significantly higher than normal (p less than 0.001) and this increase could be partly explained by the increased activity of the copper and zinc containing enzyme superoxide dismutase (p less than 0.001). Low plasma selenium and the strong relation between erythrocyte selenium and glutathione peroxidase activity we found in Down's syndrome should stimulate interest in a more detailed investigation of selenium status and metabolism of these patients.

Adolescent↗
PubMed1988

The effect of selenium on the hepatic drug metabolism and inducibility in rat.

1. Rats were fed either a normal or selenium-deficient diet for 4 weeks. The subgroup on selenium deficient diet had selenium supplementation as 3 ppm Se in the drinking water. Benzo(a)pyrene was given intraperitoneally as an inducer. 2. Se deficiency decreased glutathione peroxidase and cytochrome c-reductase activities while other activities were unchanged as compared to normal diet. 3. Selenium deficiency was a prerequisite for the induction of glutathione peroxidase, S-reductase and S-transferase enzymes. 4. Benzo(a)pyrene increased hepatic microsomal cytochrome P-450 content in rats on normal and selenium supplemented diet but not in the selenium deficient group. 5. The 7-ethoxyresorufin and 7-ethoxycoumarin deethylase, aryl hydrocarbon hydroxylase and cytochrome c-reductase activities were increased by benzo(a)pyrene in all the dietary groups. 6. The UDP-glucuronosyltransferase activity was also increased by benzo(a)pyrene in all the experimental groups and this was true with p-nitrophenol and phenolphthalein as aglycons.

Animals↗
PubMed1991

Serum selenium and coronary heart disease risk factors in southern Italian men.

The association between serum selenium concentration and a number of coronary heart disease risk factors is studied in 364 males from southern Italy participating in the Olivetti Heart Study. Selenium correlates positively and significantly with serum cholesterol (r = 0.120; P = 0.022), and this positive association persists after adjustment for age and body mass index. Selenium levels in heavy smokers are lower than both light smokers and current non-smokers, but these differences do not reach statistical significance. Selenium is not significantly associated with any of the other CHD risk factors (e.g., triglycerides, HDL cholesterol, blood pressure, age, and body mass index). It is hypothesized that the association between selenium and serum cholesterol reported in this and previous studies could be due to dietary interrelationships between selenium intake and foods that affect serum cholesterol concentrations.

Adult↗
PubMed1992

Serum selenium concentration and risk of ischaemic heart disease in a prospective cohort study of 3000 males.

Whether an association, causative or not, exists between the level of serum selenium and the risk of ischaemic heart disease (IHD) remains unsettled. We investigated the issue in a cohort of 3387 males aged 53-74 years (mean 63). Based on information about health status, life-style and socioeconomic factors given in a prefilled comprehensive questionnaire, the men were interviewed and the information validated. Following the interview, they underwent a clinical examination and had a venous blood sample drawn for the determination of a number of biochemical characteristics. Three hundred and forty-six men were excluded due to prevalent cardiovascular disease, including stroke. During the next three years (1986-1989) 107 men (approximately 3%) suffered an IHD event; 25 events were fatal. Compared to others, men with serum selenium levels less than or equal to 1 mumol/l, approximately the lowest tertile, had a 70% increased risk of IHD, relative risk (RR) with 95% confidence limits was 1.70 (1.14-2.53). After multivariate adjustment for cholesterol, social class, smoking and age, RR was 1.55 (1.00-2.39). Serum selenium level was significantly (P less than 0.05), but not strongly, correlated with a number of IHD risk factors: serum cotinine, tobacco smoking, social class, alcohol consumption, total cholesterol, hypertension, age and physical inactivity. Body mass index, HDL-cholesterol and triglycerides were not significantly associated with serum selenium. We conclude that middle-aged and elderly Danish men with serum selenium less than or equal to 1 mumol/l had a significantly increased risk of ischaemic heart disease. This association was not explained by the interrelationship of serum selenium and major cardiovascular risk factors.

Adult↗
PubMed1984

Selenium modified mutagenicity and metabolism of benzo[a]pyrene in an S9-dependent system.

Selenium added to the incubation mix containing rat-liver S9 modified both the metabolism and mutagenicity of benzo[a]pyrene (BaP) and several of its metabolites. Selenium (Na2SeO3) inhibited the S9-dependent mutagenic effects of BaP on Salmonella typhimurium strain TA100 as indicated by the number of histidine-dependent revertants counted. This inhibition was concentration-dependent over a range of 12.5 to 100 ppm. When used as the substrate the BaP metabolites 7,8-dihydrodiol, 9,10-dihydrodiol and 3-hydroxy also produced significantly fewer revertants in TA100 when selenium was included in the incubation mix. High-performance liquid chromatographic analysis of metabolites from S9-dependent metabolism of BaP indicated that selenium inhibited the formation of 3-hydroxy-BaP, 9,10-dihydrodiol, 7,8-dihydrodiol, 1,3- and 3,6-quinone. Eluting samples on an alumina column to isolate the conjugated metabolites showed that selenium caused 12% less binding to glucuronides, no significant differences in binding to sulfate esters or glutathione but the amount of unmetabolized BaP and unconjugated metabolites was increased by 48%. These results suggest that selenium inhibits S9-dependent BaP metabolism therefore reducing the mutagenic effects of this compound.

Animals↗
PubMed1985

Increased erythrocyte glutathione peroxidase activity in psoriatics consuming high-selenium drinking water at the Dead-Sea Psoriasis Treatment Center.

Erythrocyte selenium-dependent glutathione peroxidase activity was measured in psoriatic Danes, before and after their four-week balneological therapy at the Ein-Bokek International Psoriasis Treatment Center, on the Dead-Sea shore in Israel. The drinking water in Ein-Bokek was found to be rich in selenium, a trace element with anticarcinogenic properties and of great importance in human nutrition and health. The most reliable biological parameter for increase in selenium bioavailability is the erythrocytes' glutathione-peroxidase activity. As psoriasis is a proliferative skin disease, the activity of this enzyme was assayed in 35 psoriatic Danes and in 25 long-term local hotel workers, as well as in 34 volunteers drinking low-selenium water. The glutathione peroxidase activity in the psoriatic patients increased significantly during their four-week stay in Ein-Bokek. Erythrocyte glutathione peroxidase activity in the hotel workers was 50% higher than that in the healthy volunteers consuming low-selenium water. A possible role of selenium in psoriasis is suggested.

Adult↗
PubMed1983

Exposure of man to environmental selenium - an exposure commitment assessment.

Selenium is an element which occurs naturally in varying concentrations in soil and is released from industrial sources, particularly from fossil fuel combustion. Harmful effects in animals and man may result from both deficient or excessive amounts of intake. Representative values of selenium concentrations in the background environment and in man are selected from available data and a pathway analysis is performed utilizing the exposure commitment method. Dietary intake of selenium is of the order of 70 micrograms d-1. With fractional absorption of 80% and retention in the body of 90% for an effective retention time of 140 days, the estimated mean body content of selenium is 7 mg. The contribution to the body burden from inhalation intake is much less significant. The exposure evaluation is performed for total selenium in the environment and in man. The parameters may be adjusted for specific selenium compounds, if data are available, and for more particular environmental and exposure conditions as required.

Absorption↗
PubMed1984

Selenium and its interrelation with mercury in wholeblood and hair in an East Greenlandic population.

138 Blood samples and 12 hair samples from the district of Angmagssalik, East Greenland, have been analysed for selenium and mercury. It was found that selenium like mercury, was absorbed in accordance with the amount of marine food eaten. The mean blood concentration in the group eating most marine food was 173 and 186 micrograms Hg/1 for men and women, respectively, while in the group eating the lowest quantity of marine food, the mean values were 86 and 118 micrograms Hg/1. In blood, the selenium and mercury did not correlate in individuals, but only in groups according to eating habits. On a molar basis, selenium is present in blood in excess as compared to mercury, while the opposite is the case for hair. It is concluded that only part of the selenium interacts with mercury, and that blood, but not hair, reflects present dietary intake. The righ supply of selenium in relation to mercury exposure through the traditional arctic food is probably able to alleviate the hazards from dietary mercury exposure.

Adult↗
PubMed1987

Selenium accumulation in mammals exposed to contaminated California irrigation drainwater.

In May 1984, 332 mammals of 10 species were collected at Kesterson Reservoir (San Joaquin Valley, Merced Co., CA), which had received selenium-laden irrigation drainwater, and at the nearby Volta Wildlife Area, which had not. The study concentrated on the California vole (Microtus californicus); 88 were taken at Kesterson, 89 at Volta. Mean selenium concentrations in livers were as much as 522 times higher at Kesterson. There were species-to-species differences at Kesterson; higher selenium concentrations occurred in carnivorous species and/or species that feed on foods closely linked to pond water. There were also pond-to-pond differences at Kesterson; drainwater historically was delivered to Ponds 1 and 2, where concentrations in 1984 were higher, with subsequent flow to other ponds, where they were lower. Whereas none of 50 adult female voles from Kesterson was pregnant, 12 of 41 (29%) from Volta were pregnant. However, this cessation of reproductive activity at Kesterson was probably not due to selenium toxicity but could have resulted because drying conditions at Kesterson forced voles to a seed diet earlier than at Volta. One malformation was found among five embryonic litters of three species from Kesterson. Mammals seem much less susceptible to selenium-induced embryonic abnormalities than birds. No adverse impacts of selenium on wild mammals were demonstrated; however, some sensitive species might have been extirpated from Kesterson before this study began. In addition, high concentrations in small mammal species at Kesterson may threaten predatory birds and mammals that feed on them, with the endangered San Joaquin kit fox (Vulpes macrotis mutica) of particular concern.

Abnormalities, Drug-Induced↗
PubMed1989

The regional distribution of selenium in Greek cereals.

The selenium content of hard and soft wheat, barley, oats, rye and corn grown in approximately 100 different locations of Greece has been determined fluorimetrically. The mean values +/- SD for these cereal types were 0.29 +/- 0.19, 0.21 +/- 0.12, 0.16 +/- 0.10, 0.14 +/- 0.10, 0.19 +/- 0.10 and 0.12 +/- 0.08 ppm Se (dry weight basis), respectively. Based on data for selenium in corn from 96 different locations, a geobotanic map of Greece for the selenium in soil available for uptake by plants was prepared. Macedonia, West Epirus, south-east Thessaly, north-east Sterea Hellas and the Aegean Islands produce corn deficient or low in selenium, but only sporadic selenium-deficiency diseases in animals have been observed in many of these areas, probably because the farm animals are given mixed food or they are free to graze. No areas with toxic levels of selenium in soil were found.

Edible Grain↗
PubMed1994

The possible role of selenium in antioxidation in marine waders; a preliminary study.

In a marine wader, the oystercatcher (Haematopus ostralegus), the activity of the selenium-dependent enzyme glutathione peroxidase (GSH-Px) in the red blood cells (RBC) was measured. The average activity, 97 +/- 19 units/g Hb, is within the range reported for mammals. No correlation was observed between the selenium concentration and GSH-Px activity in the erythrocytes and it is calculated that only a small percentage of the selenium present in the RBC is bound to the enzyme. Therefore, it is concluded that the high selenium concentrations in the avian red cells cannot be ascribed to GSH-Px. It is argued that a function of selenium in antioxidation is still possible. The positive relationship found between selenium and iron concentrations in the tissues of the oystercatcher directs to such a role. A pitfall in the measurement of GSH-Px activity is outlined.

Animals↗
PubMed1995

Determination of selenium in serum by hydride generation atomic absorption spectrometry for calculation of daily dietary intake.

Hydride generation atomic absorption spectrometry was used to determine the selenium concentrations in 130 samples of human serum from a control group of inhabitants in the southern part of the province of Granada (Spain). The mean selenium concentration in serum was 74.9 micrograms/l. This concentration did not vary significantly (P > 0.05) in relation to the sex of the subject, with concentrations of 80.6 micrograms/l in men and 70.7 micrograms/l in women. These mean values correspond to a mean daily dietary selenium intake of 50.4 micrograms per day in men and 44.6 micrograms per day in women. A considerable number of the individuals in the study area therefore have a daily selenium intake lower than the recommended dietary allowance of 70 micrograms per day for men and 55 micrograms per day for women. Likewise, the measured selenium concentrations in the basic health zones of the area were not statistically different (P > 0.05). The differences in selenium concentration between subjects in coastal zones and mountainous zones are therefore not significant.

Analysis of Variance↗
PubMed1996

Serum selenium levels during normal pregnancy in healthy Spanish women.

In this study, we determined selenium concentrations in serum samples of healthy women (146 pregnant and 74 nonpregnant) living in the Mediterranean area of the coast of Granada (southeast Spain). The subjects were distributed in two groups: group A (pregnant women), divided into three categories according to the trimester of pregnancy, and group B (nonpregnant women). No significant differences were observed in the selenium levels either among pregnant women according to the trimester of pregnancy or in the group of nonpregnant women. No other significant differences were determined as regards the age of pregnant women (P > 0.05). Serum selenium levels are slightly lower during pregnancy. Considering that serum selenium levels affect the body selenium status, the concentrations determined establish the non-existence of selenium problems in the daily dietary intake with respect to maternal and fetal necessities during pregnancy.

Adolescent↗
PubMed1992

Selenium and arsenic in biology: their chemical forms and biological functions.

Based on the recent development of analytical methods, sensitive systems for the analysis and speciation of selenium and arsenic have been established. A palladium addition technique was developed for the accurate determination of selenium in biological samples using graphite furnace atomic absorption analysis. For the speciation of the elements, combined methods of HPLC either with ICP-AES or with ICP-MS were found to work well. These systems were applied to the elucidation of the chemical form of the elements in natural samples. Some chemical properties of the selenium-mercury complex in dolphin liver were elucidated: i.e., it was a cationic, water-soluble, low molecular weight compound containing selenium and mercury in a 1:1 molar ratio, and was shown to be different from a known selenium-mercury complex, bis(methylmercuric)selenide. The major selenium compound excreted in human urine was revealed to be other than any of those previously identified (TMSe, selenate, and selenite). TMSe, a suspected major metabolite in urine, was found, if at all, in low levels. The major water-soluble, and lipid-soluble arsenic compounds in a brown seaweed, U. pinnatifida (WAKAME), were rigorously identified, and the results were compared with other data on marine algae and animals. The major organic arsenic compounds (termed "arseno-sugars") in marine algae commonly contain 5-deoxy-5-dimethylarsinyl-ribofuranoside moiety. There are various kinds of arseno-sugar derivatives containing different side-chains attached to the anomeric position of the sugar, and the distribution of each arsenic species seems to be related to algal species. The arseno-sugar (A-XI) is present in every alga so far examined, is metabolized to lipids, and possibly may play some specific role in the algal cells. On the other hand, the major arsenic compound in fish, crustacea and molluscs has been identified as arsenobetaine, which is an arseno-analog of glycinebetaine, a very common osmo-regulator in living organisms. Arsenobetaine is not detected in marine algae while arseno-sugars are not present in marine animals except for some molluscs which contain both compounds in considerable amounts. Arsenobetaine is present in the urine of human beings who have eaten foods derived from marine animals.

Animals↗
PubMed1994

Interaction of selenium and arsenic with metallothionein: effect of vitamin B12.

The effects of selenium and arsenic on metallothionein (MT) levels were determined in vitamin B12-supplemented and depleted rats. The binding of selenium and arsenic to MT in vitro and in vivo was also investigated. Rats fed a vitamin B12-deficient diet had significant (p < 0.05), higher levels of liver MT as compared to vitamin B12-supplemented rats. Rats fed 5-9 micrograms/g selenium as selenite or 50-150 micrograms/g arsenic as arsenite showed no significant increase of MT content in the liver. However, significant increases in MT levels in liver (p < 0.01) and kidney (p < 0.05) were seen when rats were injected with 1.5 mg selenium as selenite, and increase of liver MT levels (p < 0.05) was shown when injected with 5 mg arsenic as arsenite/kg body weight. In comparison to zinc, injection of selenium or arsenic caused only a slight elevation of liver MT levels. Liver cytosolic Sephadex G-75 patterns of rats injected with both zinc and arsenic gave separate peaks for arsenic and zinc which suggest that in vivo arsenic binding to MT may be insignificant. Spectrophotometric absorption changes at 255 nm with various levels of selenium or arsenic additions to an MT solution were used to show that selenite gave a maximum absorption increase at a 1:1 molar ratio, but maximum absorption change occurred with arsenite at a molar ratio of 7:1.

Animals↗
PubMed1990

Regulation of glutathione peroxidase mRNA level by dietary selenium manipulation.

Glutathione peroxidase (GSH-Px) contains selenium at its active site as a selenocysteine moiety. We have shown that feeding mice a selenium-deficient diet for a long period caused a large decrease in the GSH-Px mRNA level as well as in GSH-Px activity both in the liver and kidneys (Toyoda, H., Himeno, S. and Imura, N. (1989) Biochim. Biophys. Acta 1008, 301-308). In the present study, the transcription rate of the GSH-Px gene was determined by a nuclear run-on assay using liver nuclei of mice fed a selenium-deficient or selenium-adequate diet. The results clearly demonstrate that the transcription rate of the GSH-Px gene was not changed by dietary selenium manipulation, indicating that dietary selenium regulates the level of GSH-Px mRNA in the post-transcriptional step.

Actins↗