Abstract
The anti-carcinogenic effects of sulforaphane (SFN) are based on the up-regulation of antioxidant enzymes (AE) and phase II enzymes (PIIE) through the transcription factor Nrf2. Current knowledge on the roles of the SFN precursor glucoraphanin (GRA) on these processes is limited. Anti-carcinogenic effects of Se depending on glutathione peroxidase (GPx) activity have also been reported. We studied effects and possible synergisms of Se and GRA on the expression and activity of a broad spectrum of AE and PIIE in jejunum, colon and the liver of rats fed diets differing in Se and GRA concentration. In all organs, GPx1 mRNA expression was 70 % to 90 % lower in Se deficiency than in Se sufficiency. GPx2 expression increased in jejunum and liver under Se deficiency and decreased in the colon. Se deficiency increased most colonic AE and PIIE compared to Se adequacy. Adequate and in particular supranutritive Se combined with GRA increased colonic AE and PIIE expression up to 3.72-fold. In the liver Se deficiency raised the expression of AE and PIIE up to 4.49-fold. GRA attenuated liver AE and PIIE response in Se deficiency. Expression- and correlation analyses revealed that Keap1 mRNA better reflects AE and PIIE gene expression than Nrf2 mRNA. We conclude that: (1) GPx1 sensitively indicates Se deficiency; (2) the influence of Se and Nrf2/Keap1 on GPx2 expression depends on the organ; (3) GRA combined with supranutritive Se may effectively protect against inflammation and colon cancer; (4) future investigations on AE and PIIE expression should consider the role of Keap1 to a higher extent.
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Abbreviations
- AE:
-
Antioxidant enzymes
- ARE:
-
Antioxidant response element
- COX:
-
Cyclooxygenase
- EPHX1:
-
Microsomal epoxide hydrolase
- GPx:
-
Glutathione peroxidase
- GRA:
-
Glucoraphanin
- GST:
-
Glutathione S-transferase
- HO1:
-
Heme oxygenase 1
- iNOS:
-
Inducible nitric oxide synthase
- Keap1:
-
Kelch-like ECH-associated protein 1
- LPS:
-
Lipopolysaccharide
- NQO1:
-
NAD(P)H:quinine oxidoreductase 1
- Nrf2:
-
Nuclear factor erythroid 2-related factor 2
- PIIE:
-
Phase II enzymes
- Se:
-
Selenium
- SFN:
-
Sulforaphane
- TNFα:
-
Tumor necrosis factor-alpha
- UGT:
-
UDP-glucuronosyltransferase
- VCAM1:
-
Vascular cell adhesion molecule 1
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Acknowledgement
We thank the Danone Foundation For Health, Haar, Germany for supporting the present experiment by a grant dedicated to study the effects of GRA supplementation on metabolic processes (Project number 2009/6). We also thank Mrs. Kumari Hiller (Jarrow Deutschland GmbH, Berlin, Germany) and Mr. Jarrow L. Rogovin (Jarrow Formulas Los Angeles, CA, USA) for providing us with the broccoli extract. We thank our students Stefanie Weber, René Priwratzky and Anna Sachno for help with the analyses within the scope of their theses.
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Blum, N.M., Mueller, K., Lippmann, D. et al. Feeding of Selenium Alone or in Combination with Glucoraphanin Differentially Affects Intestinal and Hepatic Antioxidant and Phase II Enzymes in Growing Rats. Biol Trace Elem Res 151, 384–399 (2013). https://doi.org/10.1007/s12011-012-9567-6
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DOI: https://doi.org/10.1007/s12011-012-9567-6