Effect of long-term selenium yeast intervention on activity and gene expression of antioxidant and xenobiotic metabolising enzymes in healthy elderly volunteers from the Danish Prevention of Cancer by Intervention by Selenium (PRECISE) Pilot Study

Lejla Gitte Ravn-Haren; Britta Naimi Krath; Kim Overvad; Søren Cold; Sven Moesgaard; Erik H. Larsen; Lars Ove Dragsted

doi:10.1017/S0007114507882948

Effect of long-term selenium yeast intervention on activity and gene expression of antioxidant and xenobiotic metabolising enzymes in healthy elderly volunteers from the Danish Prevention of Cancer by Intervention by Selenium (PRECISE) Pilot Study

Lejla Gitte Ravn-Haren, Britta Naimi Krath, Kim Overvad, Søren Cold, Sven Moesgaard, Erik H. Larsen, Lars Ove Dragsted

41 Citations (Scopus)

Abstract

Numerous mechanisms have been proposed to explain the anti-carcinogenic effects of Se, among them altered carcinogen metabolism. We investigated the effect of Se supplementation on activities of glutathione peroxidase (GPX), glutathione reductase (GR) and glutathione S-transferase (GST) in different blood compartments, and expression of selected phase 1 and phase 2 genes in leucocytes (GPX1, gamma-glutamylcysteine ligase catalytic subunit (GCLC), AP-1 transcription factor Fos-related antigen 1 (Fra1), NAD(P)H:quinone oxidoreductase (NQO1), and aryl hydrocarbon receptor repressor (AhRR)). Healthy elderly Danes (n 105; age 71.3 (sd 4.26) years; 36 % reporting use of multivitamin/mineral supplements) participated and were supplemented daily for 5 years with placebo, 100 mug, 200 mug or 300 mug Se as Se-enriched yeast (SelenoPrecise(R)). Blood samples were collected after 5 years of intervention. When all four groups were compared we found no effect of Se supplementation on plasma GPX or GR, on erythrocyte GPX, GR or GST, or on thrombocyte GR or GST. We found increased thrombocyte GPX activity at the two highest dosage levels in women only, but not in men. No effects on GPX1, NQO1 or AhRR gene expression were found. When all Se-supplemented groups were pooled we found significant down regulation of the expression of some phase 2 genes (GCLC, Fra1). A significant increase in AhRR gene expression with smoking was found but was independent of Se supplementation. Down regulation of phase 2 genes could increase the risk of cancer. However, further studies are needed to establish whether the observed effect in leucocytes reflects a similar expression pattern in target tissues.

Original language	English
Journal	British Journal of Nutrition
Volume	99
Issue number	6
Pages (from-to)	1190-1198
Number of pages	9
ISSN	0007-1145
DOIs	https://doi.org/10.1017/S0007114507882948
Publication status	Published - 2007

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Ravn-Haren, L. G., Krath, B. N., Overvad, K., Cold, S., Moesgaard, S., Larsen, E. H., & Dragsted, L. O. (2007). Effect of long-term selenium yeast intervention on activity and gene expression of antioxidant and xenobiotic metabolising enzymes in healthy elderly volunteers from the Danish Prevention of Cancer by Intervention by Selenium (PRECISE) Pilot Study. British Journal of Nutrition, 99(6), 1190-1198. https://doi.org/10.1017/S0007114507882948

Effect of long-term selenium yeast intervention on activity and gene expression of antioxidant and xenobiotic metabolising enzymes in healthy elderly volunteers from the Danish Prevention of Cancer by Intervention by Selenium (PRECISE) Pilot Study. / Ravn-Haren, Lejla Gitte; Krath, Britta Naimi; Overvad, Kim et al.

In: British Journal of Nutrition, Vol. 99, No. 6, 2007, p. 1190-1198.

Research output: Contribution to journal › Journal article › Research › peer-review

Ravn-Haren, LG, Krath, BN, Overvad, K, Cold, S, Moesgaard, S, Larsen, EH & Dragsted, LO 2007, 'Effect of long-term selenium yeast intervention on activity and gene expression of antioxidant and xenobiotic metabolising enzymes in healthy elderly volunteers from the Danish Prevention of Cancer by Intervention by Selenium (PRECISE) Pilot Study', British Journal of Nutrition, vol. 99, no. 6, pp. 1190-1198. https://doi.org/10.1017/S0007114507882948

Ravn-Haren LG, Krath BN, Overvad K, Cold S, Moesgaard S, Larsen EH et al. Effect of long-term selenium yeast intervention on activity and gene expression of antioxidant and xenobiotic metabolising enzymes in healthy elderly volunteers from the Danish Prevention of Cancer by Intervention by Selenium (PRECISE) Pilot Study. British Journal of Nutrition. 2007;99(6):1190-1198. doi: 10.1017/S0007114507882948

Ravn-Haren, Lejla Gitte ; Krath, Britta Naimi ; Overvad, Kim et al. / Effect of long-term selenium yeast intervention on activity and gene expression of antioxidant and xenobiotic metabolising enzymes in healthy elderly volunteers from the Danish Prevention of Cancer by Intervention by Selenium (PRECISE) Pilot Study. In: British Journal of Nutrition. 2007 ; Vol. 99, No. 6. pp. 1190-1198.

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abstract = "Numerous mechanisms have been proposed to explain the anti-carcinogenic effects of Se, among them altered carcinogen metabolism. We investigated the effect of Se supplementation on activities of glutathione peroxidase (GPX), glutathione reductase (GR) and glutathione S-transferase (GST) in different blood compartments, and expression of selected phase 1 and phase 2 genes in leucocytes (GPX1, gamma-glutamylcysteine ligase catalytic subunit (GCLC), AP-1 transcription factor Fos-related antigen 1 (Fra1), NAD(P)H:quinone oxidoreductase (NQO1), and aryl hydrocarbon receptor repressor (AhRR)). Healthy elderly Danes (n 105; age 71.3 (sd 4.26) years; 36 % reporting use of multivitamin/mineral supplements) participated and were supplemented daily for 5 years with placebo, 100 mug, 200 mug or 300 mug Se as Se-enriched yeast (SelenoPrecise(R)). Blood samples were collected after 5 years of intervention. When all four groups were compared we found no effect of Se supplementation on plasma GPX or GR, on erythrocyte GPX, GR or GST, or on thrombocyte GR or GST. We found increased thrombocyte GPX activity at the two highest dosage levels in women only, but not in men. No effects on GPX1, NQO1 or AhRR gene expression were found. When all Se-supplemented groups were pooled we found significant down regulation of the expression of some phase 2 genes (GCLC, Fra1). A significant increase in AhRR gene expression with smoking was found but was independent of Se supplementation. Down regulation of phase 2 genes could increase the risk of cancer. However, further studies are needed to establish whether the observed effect in leucocytes reflects a similar expression pattern in target tissues.",

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AU - Ravn-Haren, Lejla Gitte

AU - Krath, Britta Naimi

AU - Overvad, Kim

AU - Cold, Søren

AU - Moesgaard, Sven

AU - Larsen, Erik H.

AU - Dragsted, Lars Ove

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N2 - Numerous mechanisms have been proposed to explain the anti-carcinogenic effects of Se, among them altered carcinogen metabolism. We investigated the effect of Se supplementation on activities of glutathione peroxidase (GPX), glutathione reductase (GR) and glutathione S-transferase (GST) in different blood compartments, and expression of selected phase 1 and phase 2 genes in leucocytes (GPX1, gamma-glutamylcysteine ligase catalytic subunit (GCLC), AP-1 transcription factor Fos-related antigen 1 (Fra1), NAD(P)H:quinone oxidoreductase (NQO1), and aryl hydrocarbon receptor repressor (AhRR)). Healthy elderly Danes (n 105; age 71.3 (sd 4.26) years; 36 % reporting use of multivitamin/mineral supplements) participated and were supplemented daily for 5 years with placebo, 100 mug, 200 mug or 300 mug Se as Se-enriched yeast (SelenoPrecise(R)). Blood samples were collected after 5 years of intervention. When all four groups were compared we found no effect of Se supplementation on plasma GPX or GR, on erythrocyte GPX, GR or GST, or on thrombocyte GR or GST. We found increased thrombocyte GPX activity at the two highest dosage levels in women only, but not in men. No effects on GPX1, NQO1 or AhRR gene expression were found. When all Se-supplemented groups were pooled we found significant down regulation of the expression of some phase 2 genes (GCLC, Fra1). A significant increase in AhRR gene expression with smoking was found but was independent of Se supplementation. Down regulation of phase 2 genes could increase the risk of cancer. However, further studies are needed to establish whether the observed effect in leucocytes reflects a similar expression pattern in target tissues.

AB - Numerous mechanisms have been proposed to explain the anti-carcinogenic effects of Se, among them altered carcinogen metabolism. We investigated the effect of Se supplementation on activities of glutathione peroxidase (GPX), glutathione reductase (GR) and glutathione S-transferase (GST) in different blood compartments, and expression of selected phase 1 and phase 2 genes in leucocytes (GPX1, gamma-glutamylcysteine ligase catalytic subunit (GCLC), AP-1 transcription factor Fos-related antigen 1 (Fra1), NAD(P)H:quinone oxidoreductase (NQO1), and aryl hydrocarbon receptor repressor (AhRR)). Healthy elderly Danes (n 105; age 71.3 (sd 4.26) years; 36 % reporting use of multivitamin/mineral supplements) participated and were supplemented daily for 5 years with placebo, 100 mug, 200 mug or 300 mug Se as Se-enriched yeast (SelenoPrecise(R)). Blood samples were collected after 5 years of intervention. When all four groups were compared we found no effect of Se supplementation on plasma GPX or GR, on erythrocyte GPX, GR or GST, or on thrombocyte GR or GST. We found increased thrombocyte GPX activity at the two highest dosage levels in women only, but not in men. No effects on GPX1, NQO1 or AhRR gene expression were found. When all Se-supplemented groups were pooled we found significant down regulation of the expression of some phase 2 genes (GCLC, Fra1). A significant increase in AhRR gene expression with smoking was found but was independent of Se supplementation. Down regulation of phase 2 genes could increase the risk of cancer. However, further studies are needed to establish whether the observed effect in leucocytes reflects a similar expression pattern in target tissues.

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