Association of selenium status and blood glutathione concentrations in blacks and whites.

Selenium deficiency has been linked with increased cancer risk and, in some studies, selenium supplementation was protective against certain cancers. Previous studies have suggested that selenium chemoprevention may involve reduced oxidative stress through enhanced glutathione (GSH). Our objectives were to examine the relationships between selenium and GSH in the blood and the modifying effects of race and sex in free-living adults and individuals supplemented with selenium. Plasma selenium concentrations and free and bound GSH concentrations and γ-glutamyl cysteine ligase (GCL) activity in the blood were measured in 336 healthy adults (161 Blacks, 175 Whites). Plasma selenium and blood GSH were also measured in 36 healthy men from our previously conducted placebo-controlled trial of selenium-enriched yeast (247 µg/day for 9 mo). In free-living adults, selenium concentrations were associated with increased blood GSH concentration and GCL activity (P < 0.05). Further, selenium was significantly higher in Whites than in Blacks (P < 0.01). After 9 mo of supplementation, plasma selenium increased 114% in Whites and 50% in Blacks (P < 0.05), and blood GSH increased 35% in Whites (P < 0.05) but was unchanged in Blacks. These results indicate a direct association between selenium and GSH in the blood of both free-living and selenium-supplemented individuals, with race being an important modifying factor.

The organoselenium compound 1,4-phenylenebis(methylene)selenocyanate inhibits 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced tumorgenesis and enhances glutathione-related antioxidant levels in A/J mouse lung.

Selenium, in the form of 1,4-phenylenebis(methylene)selenocyanate (p-XSC) but not Se-enriched yeast (Se-yeast), was highly effective at inhibiting lung tumors induced by the tobacco specific nitrosamine (TSNA) 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in A/J mice and at reducing NNK-induced DNA methylation and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in the lung. Our goal was to determine if p-XSC but not Se-yeast is effective at inducing levels of glutathione (GSH)-related antioxidants and reducing markers of GSH oxidation in the NNK-induced lung tumor model. In the first bioassay, 6-week-old mice were fed either control or experimental diets (containing 10 ppm as selenium from p-XSC or Se-yeast) and, beginning at 8 weeks of age, received NNK (3 micromol) by gavage once weekly for 8 weeks. After 18 weeks, p-XSC significantly reduced NNK-induced tumor burden by 74% (10.4 +/- 6.0 versus 2.7 +/- 1.5 tumors/mouse, P < 0.001) and tumor incidence from 96% to 68% (P < 0.01), whereas, Se-yeast had no effect. Lung GSH levels were unchanged by either NNK or Se-yeast, but were increased 70% in mice treated with both NNK and p-XSC (P < 0.01) and 41% in mice treated with p-XSC alone. In the second bioassay, the time course of effects of p-XSC was examined. As early as one week after initiation of p-XSC feeding lung and blood selenium levels were increased nearly six- and two-fold, respectively. Increases of 120% for GSH and 65% for Cys were observed in p-XSC groups compared to controls within one week after initiation of p-XSC feeding (P < 0.01). The levels of protein-bound:free GSH ratios and Cys ratios were significantly decreased in p-XSC-treated mice, regardless of NNK status, suggesting a decrease in the levels of oxidative stress. Altogether, these results indicate that p-XSC is a potent inducer of GSH and related thiol antioxidants in the lung leading to decreased levels of oxidative stress and suggest that p-XSC inhibits tumor formation, in part, by protecting against oxidative damage.

Influence of selenium-enriched yeast supplementation on biomarkers of oxidative damage and hormone status in healthy adult males: a clinical pilot study.

The mechanisms responsible for the protective role of selenium against the development of prostate cancer remain to be determined (L. C. Clark et al., J. Am. Med. Assoc., 276: 1957-1963, 1996). In the present study, we tested the hypothesis that selenium supplementation reduces oxidative stress. A secondary aim was to determine whether selenium-induced changes in testosterone (T) metabolism may also be involved. To this end, we conducted a double-blind, randomized, placebo-controlled trial of 247 micro g selenium/day administered p.o. in the form of Se-enriched yeast. Study subjects were 36 healthy adult males, 11 blacks and 25 whites, 19-43 years of age. Supplementation occurred over the first 9 months, after which all subjects were placed on placebo for an additional 3 months. Blood and urine were collected at baseline and after 3, 9, and 12 months. In the selenium group, plasma selenium levels were 2-fold higher than baseline values after 3 and 9 months and returned to 136% of baseline after 12 months (P < 0.0001), whereas in the placebo group, levels were unchanged. A 32% increase in blood glutathione (GSH) levels was observed after 9 months in the selenium group only (P < 0.05). This change coincided with a 26% decrease in protein-bound GSH (bGSH) and a 44% decrease in bGSH:GSH ratios (P < 0.05). The changes in GSH and bGSH were highly correlated with changes in plasma selenium concentrations and may reflect a decrease in oxidative stress. No changes were observed in either group for plasma T, dihydrotestosterone (DHT) or DHT:T ratios, suggesting that selenium had no effect on the alpha-reductase involved in the conversion of T to DHT. A small but significant decrease in prostate-specific antigen levels was observed after 3 and 9 months (P < 0.001), and this difference disappeared after 12 months. Future trials will test the above hypothesis in prostate cancer patients and in subjects at high risk for prostate cancer.