Selenium levels of Estonians.

BACKGROUND: The objective of this study is to sum up the dietary selenium intake of the Estonian people according to the serum selenium concentrations. SUBJECTS/METHODS: This research compiles the information published in the literature about the levels of selenium in the serum of the Estonian people. We compare these results with the findings obtained from the analyses of serum samples gathered by us in the 1990s in Estonia. RESULTS: The selenium concentration in sera of 404 Estonians ranged from 26 to 116 microg/l; the mean was 75 microg/l. The selenium contents of Estonians were at a similar level as reported for Finns before the selenium supplementation of fertilizers carried out in Finland in 1984. CONCLUSION: In view of the selenium concentration in the sera, we suggest that the dietary selenium intake among the Estonian people might be scarce, and Estonian authorities should consider in their nutrition policies the possible low intake of selenium of Estonians.

Selenium in pregnancy: is selenium an active defective ion against environmental chemical stress?

Transportation of selenium from mother to fetus and its possible effects on mother's zinc, copper, cadmium, and mercury levels were studied together during the first trimester and at term in 216 mothers. Mothers came from three geographical places with different selenium intakes. The role of selenium as a biomarker for the vital function was estimated by studying the associations between tissue or blood selenium content and placental cytochrome P450 enzyme activities and the newborn's birth weight. Regardless of the selenium intake of the mothers, higher concentrations were found in the cord blood than in mother's blood reflecting active transportation of selenium to the fetus. Active smoking was associated with higher placental selenium concentrations like it is associated with higher placental zinc concentrations. When the cadmium concentrations were high in placenta, as in smokers, the transfer of selenium from blood to placenta was increased, decreasing the selenium levels in blood. On the other hand, the high selenium concentrations in blood were connected to lower cadmium concentrations in placenta also in nonsmokers. Selenium had correlations with copper and zinc. ECOD activity in placental tissue, mercury in mothers' hair, mothers' age, and selenium concentrations in cord blood and placental selenium all seem to have connections with xenobiotic-metabolizing enzymes linked effects among mothers. These data suggest that selenium has an active role in the mother's defense systems against the toxicity of environmental pollutants and the constituents of cigarette smoke.

Effect of supplementation with organic selenium on mercury status as measured by mercury in pubic hair.

The purpose of this study was to evaluate the effect of four months of yeast-based selenium supplementation on selenium and mercury status in subjects with low serum selenium. The study was carried out in Rakvere, Estonia. Pubic hair mercury, serum selenium and blood selenium concentrations in 23 subjects (serum selenium < 90 micrograms/l) were investigated before and after selenium supplementation. Thirteen subjects were randomized into the selenium supplementation group and ten into the placebo group. The selenium supplementation group received daily 100 micrograms of selenomethionine. Selenium supplementation reduced pubic hair mercury level by 34% (p = 0.005) and elevated serum selenium by 73% and blood selenium by 59% in the supplemented group (p < 0.001 for both). The study indicates that mercury accumulation in pubic hair can be reduced by dietary supplementation with small daily amounts of organic selenium in a short range of time.

Accumulation of cadmium, zinc, and copper in maternal blood and developmental placental tissue: differences between Finland, Estonia, and St. Petersburg.

Cadmium, zinc, and copper from placental tissue and blood samples at the first trimester (n = 64) and at term (n = 152) were analyzed; the welfare of newborns and placental 7-ethoxycoumarin O-deethylase (ECOD) activities in vitro were determined. The study material was collected from Finland, Estonia, and Russia. The results demonstrate that Cd starts to accumulate in the placenta during the first trimester and that Zn and Cu contents were significantly higher at the first trimester than at term. Among nonsmokers a negative correlation was found between placental Cu content and birth weight of neonates. Among smokers a positive correlation between placental Zn content and birth weight and ECOD activity was found. The birth weights correlated inversely with the length of time the mothers smoked. The highest Cd concentrations were detected in the samples collected from St. Petersburg. The data demonstrate an inverse accumulation of Zn and Cd throughout the pregnancy in the placenta and maternal blood samples. Zn may act as a positive marker or even an enzymatic enhancement for the human placental vital functions. Smoking, parity, age, and especially the place of residence affect the Cd, Zn, and Cu contents and ratios in placenta and mother's blood.

Maternal drug abuse and human term placental xenobiotic and steroid metabolizing enzymes in vitro.

We evaluated the impact of maternal drug abuse at term on human placental cytochrome P450 (CYP)-mediated (Phase I) xenobiotic and steroid-metabolizing activities [aromatase, 7-ethoxyresorufin O-deethylase (EROD), 7-ethoxycoumarin O-deethylase (ECOD), pyrene 1-hydroxylase (P1OH), and testosterone hydroxylase], and androstenedione-forming isomerase, NADPH quinone oxidoreductase (Phase II), UDP-glucuronosyltransferase (UGT), and glutathione S-transferase (GST) activities in vitro. Overall, the formation of androstenedione, P1OH, and testosterone hydroxylase was statistically significant between control and drug-abusing subjects; we observed no significant differences in any other of the phase I and II activities. In placentas from drug-abusing mothers, we found significant correlations between ECOD and P1OH activities (p < 0. 001), but not between ECOD and aromatase or P1OH and EROD activities; we also found significant correlations between blood cotinine and UGT activities (p < 0.01). In contrast, in controls (mothers who did not abuse drugs but did smoke cigarettes), the P1OH activity correlated with ECOD, EROD (p < 0.001), and testosterone hydroxylase (p < 0.001) activities. Our results (wider variation in ECOD activity among tissue from drug-abusing mothers and the significant correlation between P1OH and ECOD activities, but not with aromatase or EROD activities) indicate that maternal drug abuse results in an additive effect in enhancing placental xenobiotic metabolizing enzymes when the mother also smokes cigarettes; this may be due to enhancing a "silent" CYP form, or a new placental CYP form may be activated. The change in the steroid metabolism profile in vitro suggests that maternal drug abuse may alter normal hormonal homeostasis during pregnancy.

Mercury-binding capacity of organic and inorganic selenium in rat blood and liver.

The mercury-binding capacity of seleno-DL-methionine and selenium dioxide was assessed in male Wistar rats. Mercury was supplied as fish loaves made of northern pike or rainbow trout. We used a selenium concentration of 3.4 mg/kg fish, about sixfold compared to the equivalent quantity of mercury. Seleno-DL-methionine had a tendency to increase both methyl mercury and total mercury in blood, although it also seemed to reduce the proportion of methyl mercury of total mercury. Selenium dioxide lowered mercury levels by 24-29% both in the blood and in the liver of rats that were fed with northern pike.

Association of cadmium with human breast cancer.

The carcinogenic potential of cadmium might be affected by several factors such as smoking, hormones and presence of other metals, such as selenium and zinc. Cadmium was analyzed in breast-fat tissue of 43 breast cancer patients and 32 healthy control subjects. Patients were thoroughly characterized according to such variables as stage of cancer, smoking habits, and number of children. Correlation of cadmium levels with these variables, with hormone receptors, and with previously reported selenium and zinc were all analyzed. The mean cadmium concentration found in breast cancer patients (20.4 +/- 17.5 micrograms/g) did not differ significantly from that of the healthy controls (31.7 +/- 39.4 micrograms/g). However, unexpectedly high concentrations of cadmium (3.2-86.9 vs. 0.1-160.4 micrograms/g) were found in breast samples, which may indicate that cadmium binding proteins exist in human breast tissue. Correlation of cadmium with smoking rate of cancer patients was positive (Rs = 0.0505, p < 0.05). Correlation of cadmium with estrogen receptors in breast cancer was suggestive (Rs = 0.309, 28 cases, P = 0.06). No correlation was found with other trace elements such as selenium, zinc and copper. These results seem neither to prove nor to disprove the role of cadmium in breast cancer initiation, promotion or progression.

Trends in the concentrations of mercury, copper, zinc and selenium in inhabitants of north-eastern Finnish Lapland in 1982-1991. A pilot study.

The heavy industry on the Murmansk region in Russia is releasing huge amounts of waste into the air, including heavy metals and sulphur compounds. To investigate the temporal trend in exposure to certain heavy metals among the inhabitants of north-eastern Finland, a pilot study was carried out involving serum and hair samples from group of 11 persons monitored in Ivalo in 1982 and 1991. A further 6 persons residing near the Russian border in Nellim and 10 adults and 2 children residing in the Sevettijärvi-Näätämö area also participated in 1991. In addition, serum and hair samples were also obtained from controls residing in the Helsinki area. Total mercury content, determined by flow injection analysis and the amalgam system, pointed to a decrease in concentrations in the hair of inhabitants of Ivalo, whereas mercury concentrations were found to be higher in those residing near the Russian border. The mercury concentrations in the hair of northern inhabitants were about 4 times greater than those in the hair of the people from southern Finland on average. No trend towards an increase or decrease was found in copper and zinc concentrations in hair and serum as determined by atomic absorption spectrometry in employing the flame technique. Selenium has been thought to act as an antagonist to the heavy metal mercury. The addition of selenium to fertilisers began in Finland in 1984, but such fertilisers have not been used widely in Lapland. Selenium concentrations, determined by flameless atomic absorption spectrometry, showed an increase with time in the inhabitants of northern Finland. Selenium concentrations were higher in the residents of Lapland than in the southern Finns, but this difference occurred after the addition of selenium to fertilisers has begun to be less common.

Intake of mercury from fish, lipid peroxidation, and the risk of myocardial infarction and coronary, cardiovascular, and any death in eastern Finnish men.

BACKGROUND: Even though previous studies have suggested an association between high fish intake and reduced coronary heart disease (CHD) mortality, men in Eastern Finland, who have a high fish intake, have an exceptionally high CHD mortality. We hypothesized that this paradox could be in part explained by high mercury content in fish. METHODS AND RESULTS: We studied the relation of the dietary intake of fish and mercury, as well as hair content and urinary excretion of mercury, to the risk of acute myocardial infarction (AMI) and death from CHD, cardiovascular disease (CVD), and any cause in 1833 men aged 42 to 60 years who were free of clinical CHD, stroke, claudication, and cancer. Of these, 73 experienced an AMI in 2 to 7 years. Of the 78 decreased men, 18 died of CHD and 24 died of CVD. Men who had consumed local nonfatty fish species had elevated hair mercury contents. In Cox models with the major cardiovascular risk factors as covariates, dietary intakes of fish and mercury were associated with significantly increased risk of AMI and death from CHD, CVD, and any death. Men in the highest tertile (> or = 2.0 micrograms/g) of hair mercury content had a 2.0-fold (95% confidence interval, 1.2 to 3.1; P = .005) age- and CHD-adjusted risk of AMI and a 2.9-fold (95% CI, 1.2 to 6.6; P = .014) adjusted risk of cardiovascular death compared with those with a lower hair mercury content. In a nested case-control subsample, the 24-hour urinary mercury excretion had a significant (P = .042) independent association with the risk of AMI. Both the hair and urinary mercury associated significantly with titers of immune complexes containing oxidized LDL. CONCLUSIONS: These data suggest that a high intake of mercury from nonfatty freshwater fish and the consequent accumulation of mercury in the body are associated with an excess risk of AMI as well as death from CHD, CVD, and any cause in Eastern Finnish men and this increased risk may be due to the promotion of lipid peroxidation by mercury.

Copper and zinc concentrations of abdominal aorta and liver in patients with infrarenal abdominal aortic aneurysm or aortoiliacal occlusive disease.

It has been suggested that low copper concentrations in tissues could be a risk factor in the development of infrarenal abdominal aortic aneurysms (AAA). To further elucidate this argument, liver and abdominal aortic specimens were obtained from 19 patients with an AAA and 26 patients with aortoiliac occlusive disease (AIOD) during an operation. After tissue breakdown and liquefaction, the samples were tested for copper and zinc with atomic absorption spectrophotometry. The mean aortic copper level was 3.8 (microgram/g dry weight) in the AAA-group and 3.2 in the AIOD-group. The liver copper values were 27.7 and 25.9 respectively. The zinc concentrations in AAA- and AIOD-groups were 61.1 (microgram/g dry weight) and 62.8 for the aortas and 207.9 and 191.7 for liver specimens, respectively. There were no statistically significant differences between the two groups regarding the copper and zinc concentrations found in the aorta or liver specimens. On the basis of our findings, it seems unlikely that copper and zinc in the aortic wall or in the liver would play an important role in the pathogenesis of infrarenal abdominal aortic aneurysms.

Screening of effects of selenomethionine-enriched yeast supplementation on various immunological and chemical parameters of skin and blood in psoriatic patients.

Selenium (Se) is known to affect the immune system, and decreased Se-levels in blood of patients with moderate or severe psoriasis have been reported. In this study, the effect of Se-supplementation (400 micrograms/day for 6 weeks as Se-yeast, containing about 70% selenomethionine, SeMet) on skin and blood Se-content, on skin glutathione peroxidase activity and on various chemical and immunological parameters of blood and skin was investigated in 7 psoriatic patients. Before the SeMet-supplementation, serum and blood Se-levels were at the normal range, but they increased 42-45% during the Se-dosage, while zinc levels remained unchanged. Se-dependent glutathione peroxidase activity in both normal and lesional psoriatic skin remained unchanged during the trial, although a small net Se-uptake was detected. At the same time, a slight but statistically significant increase in the number of CD4+ T-cells was observed in the reticular dermis of the psoriatic lesions whereas the numbers of CD8+, CD11c+, and CD1+ cells were not significantly altered. Also, a relatively high number of patients (3 out of 7) showed a strongly reduced number of gamma/delta T-lymphocytes or increased CD8+ T-cells (2 patients) in peripheral blood. However, SeMet-supplementation was not related to these abnormalities or to the number of other peripheral blood immunocytes or to serum immunoglobulin levels. In addition, no marked effect on the clinical condition of the patients was observed. This pilot study suggests that SeMet may be able to modulate the immunological mechanism of psoriatic lesions by increasing the number of CD4+ T-cells.

Effects of antioxidant supplementation on platelet function: a randomized pair-matched, placebo-controlled, double-blind trial in men with low antioxidant status.

We investigated the effect on platelet function of supplementing men with low antioxidant status with 600 mg ascorbic acid, 300 mg alpha-tocopherol, 27 mg beta-carotene, and 75 micrograms selenium in yeast daily. Eighty men were randomly assigned in pairs (matched for smoking, baseline antioxidant status, and time and day of entry) by use of a double-blind design to receive supplement or placebo for 5 mo. Compared with 39 control subjects, 39 antioxidant-supplemented men experienced the following net reductions during the double-blind period: 20% (P = 0.012) in serum lipid peroxides, 24% (P = 0.035) in ADP-induced platelet aggregation, 42% (P = 0.040) in the rate of ATP release during aggregation, 51% (P = 0.018) in serum (platelet-produced) thromboxane B2, and 29% (P = 0.024) in plasma beta-thromboglobulin concentration. The data support our hypothesis that antioxidant supplementation of men with low antioxidant status and high fat intake reduces lipid peroxidation, the capacity of platelets to aggregate and to produce thromboxane A2, and in vivo platelet activation.

Interactions of serum copper, selenium, and low density lipoprotein cholesterol in atherogenesis.

OBJECTIVE: To investigate the interactions between serum copper, selenium, and low density lipoprotein cholesterol concentrations with regard to the progression of carotid atherosclerosis. DESIGN: Longitudinal study of a cohort of middle aged men followed up for 24 months. SETTING: Epidemiological survey of the population of seven communities in eastern Finland. SUBJECTS: 126 men aged 42, 48, 54, or 60 at examination randomly selected from a population based sample of 2682 men. MAIN OUTCOME MEASURES: Increase in maximal carotid intima media thickness. RESULTS: The mean increase in the maximal common carotid intima media thickness after two years was greater in men with high serum copper concentrations (0.16 mm compared with 0.08 mm in men with concentrations less than 17.6 mumol/l; p = 0.010), those with low serum selenium concentrations (0.15 mm compared with 0.09 mm in men with concentrations greater than or equal to 1.40 mumol/l; p = 0.035), and those with raised serum low density lipoprotein cholesterol concentrations (0.15 mm compared with 0.08 mm in men with concentrations less than 4.0 mmol/l; p = 0.032) after adjustment for age and cigarette pack years in a three way analysis of covariance. A raised serum low density lipoprotein concentration was associated with accelerated progression of atherosclerosis only in men with higher than median serum copper concentrations (net difference 0.22 mm; p less than 0.001 for two way interaction), and this synergism was even more pronounced in men with serum selenium concentrations below the median value (net difference 0.41 mm; p = 0.042 for three way interaction). CONCLUSION: These data provide evidence of a synergistic effect of copper (a pro-oxidant), a low serum concentration of selenium (a cofactor of an enzyme that scavenges free radicals), and low density lipoprotein cholesterol concentration in atherogenesis.

Metabolism, cellular actions, and cytotoxicity of selenomethionine in cultured cells.

Selenomethionine metabolism and the biochemical basis for its cytotoxicity were analyzed in cultured human and murine lymphoid cells. The metabolic pathways were also addressed, using purified mammalian enzymes and crude tissue extracts. Selenomethionine was found to be effectively metabolized to S-adenosylmethionine analog, and that analog was further metabolized in transmethylation reactions and in polyamine synthesis, similarly to the corresponding sulphur metabolites of methionine. Selenomethionine did not block these pathways, nor was there a specific block on the synthesis of DNA, RNA, or proteins when added to the culture medium. Selenomethionine showed cytotoxicity at above 40 microM levels. Yet, low selenomethionine levels (10 microM) could replace methionine and support cell growth in the absence of methionine. Selenomethionine toxicity took place concomitantly with changes in S-adenosylmethionine pools. D-form was less cytotoxic than L-form. Methionine concentration modified the cytotoxicity. Together, this indicates that selenomethionine uptake and enzymic metabolism are involved in the cytotoxicity in a yet unknown way.

Human seminal plasma cadmium: comparison with fertility and smoking habits.

Cadmium, selenium and zinc were determined in seminal plasma and serum of 64 men by atomic absorption spectrometry (AAS). The mean (+/- SD) cadmium concentrations in seminal plasma and serum were 0.22 +/- 0.22 micrograms and 0.28 +/- 0.10 micrograms, respectively, but they did not correlate with each other. Smokers (n = 31) had significantly (p less than 0.01) higher serum cadmium concentrations than non-smokers (n = 31). Also seminal plasma cadmium in smokers was elevated, but a significant difference to non-smokers was only found if more than 20 cigarettes were consumed daily. No differences were found in semen quality and fertility between smokers and non-smokers. The seminal plasma cadmium had no correlation to selenium or zinc which, however, displayed a positive correlation (r = 0.852, p less than 0.001) to each other. It is concluded that smoking increases the exposure to cadmium. Although no obvious reproductive suppression was observed, heavy smoking may possibly enhance toxic effects in men under other detrimental exposures.

PIP: Cadmium, selenium, and zinc were determined in seminal plasma and serum of 64 men by atomic absorption spectrometry (AAS). The mean (+or- SD) cadmium concentrations in seminal plasma and serum were 0.22 +or- 0.22 mcg and 0.28 +or- 0.10 mcg, respectively, but they did not correlate with each other. Smokers (n=31) had significantly (p0.01) higher serum cadmium concentrations than nonsmokers (n=31). Also, seminal plasma cadmium in smokers was elevated, but a significant difference to nonsmokers was only found if 20 cigarettes were consumed daily. No differences were found in semen quality and fertility between smokers and nonsmokers. The seminal plasma cadmium had no correlation to selenium or zinc which, however, displayed a positive correlation (r=0.852, p 0.001) to each other. It is concluded that smoking increases the exposure to cadmium. Although no obvious reproductive suppression was observed, heavy smoking may possible enhance toxic effects in men under other detrimental exposures. (author's)

Blood pressure, dietary fats, and antioxidants.

We investigated the association of dietary fatty acids and antioxidants with blood pressure in 722 eastern Finnish men aged 54 y, examined in the Kuopio Ischaemic Heart Disease Risk Factor Study in 1984-86. Men with self-reported hypertension or cerebrovascular disease or under antihypertensive medication were excluded. Allowing for the major anthropometric, dietary, medical, and psychological determinants of blood pressure in multivariate regression analyses, both plasma ascorbic acid (p = 0.0008) and serum selenium (p = 0.0017) concentrations had a moderate, independent inverse association, estimated dietary intake of saturated fatty acids had a positive association (p = 0.013), and estimated dietary intake of linolenic acid had an inverse (p = 0.048) association with the mean resting blood pressure. The marked elevation of blood pressure at the lowest levels of plasma ascorbic acid and serum Se concentrations supports the hypothesis that antioxidants play a role in the etiology of hypertension.

Selenium and glutathione peroxidase in seminal plasma of men and bulls.

High levels of selenium and glutathione peroxidase (GSH-Px) were found in bull seminal plasma but low concentrations in human seminal plasma. In man the seminal plasma selenium was associated with two macromolecules separable by gel filtration, but no GSH-Px was found in the same fractions. Selenium in bull seminal plasma was associated with two proteins, which could be separated by gel filtration and anion exchange chromatography. Both macromolecules coeluted with GSH-Px activity and had identical optima at pH 7.0. Their responses to thermal treatment, however, differed. Seminal vesicle secretory fluid in the bull contained both these proteins, while the larger molecule was also found in fractionations of ampulla, prostate and Cowper's glands. The larger enzyme form is evidently a tetramer of the smaller one. Both enzyme forms were extremely sensitive to heavy metals and some divalent metal ions. GSH caused an activation while other reducing agents were suppressive. Triton X-100 had no effect, while sodium deoxycholate was inhibitory. These properties are typical for a phospholipid hydroperoxide GSH-Px. It is concluded that this selenium-dependent enzyme may be important in the protection of bovine spermatozoa against damage caused by oxygen radicals, while in man such a mechanism is not functional.