|Hintze, Korry - NORTH DAKOTA ST UNIV|
|Keck, Anna-Sigrid - UNIV OF ILLINOIS|
|Jeffery, Elizabeth - UNIV OF ILLINOIS|
Submitted to: Journal of Nutritional Biochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: December 10, 2002
Publication Date: April 1, 2003
Citation: Hintze, K.J., Keck, A-S., Finley, J.W. and Jeffery, E.H. Induction of hepatic thioredoxin reductase activity by sulforaphane, both in Hepa 1c1c7 cells and in male Fisher 344 rats. J. Nutr. Biochem. 14: 173-179, 2003. Interpretive Summary: Thioredoxin reductase is an enzyme that increases in amount and activity with increases in dietary selenium. We have investigated whether this enzyme may be "turned on" in animals by minor compounds present in plants, and whether this is part of an overall response to reduce cancer risk in animals. We have demonstrated that the amount of thioredoxin reductase in cells can be increased by feeding the minor plant compounds sulforaphane (found in large concentrations in broccoli) to rats or added directly to the growth medium of cultured cells. Dietary selenium has been demonstrated to be anticarcinogenic in animal and human studies. Elevated concentrations of thioredoxin reductase resulting from increased dietary selenium may partially explain the anticarcinogenic effect of selenium. Therefore, diets high in both selenium and sulforaphane may be especially beneficial.
Technical Abstract: Sulforaphane (SF), a glucosinolate-derived isothiocyanate found in cruciferous vegetables, is considered an anticarcinogenic component in broccoli. Sulforaphane induces a battery of detoxification enzymes that may be part of a coordinated host-defense response. The objective of the present study was to test whether thioredoxin reductase (TR), a selenoprotein, is part of this response. TR activity was measured in livers of rats fed diets containing SF and/or broccoli and mouse hepatoma cells cultured in the presence of SF. Animals fed purified sulforaphane and 20% broccoli had significantly greater hepatic TR activity than animals on a control AIN 76-B40 diet. However, gluthathione peroxidase (GSH-PX), a second selenium-dependent enzyme with antioxidant activity, was downregulated in rats fed both SF and broccoli, compared to the control diet. In mouse hepatoma Hepalclc7 cells, Se (2.5 uM) plus SF (2.0 uM) significantly increased TR activity more than either treatment alone. All treatments with added Se or SF caused significantly greater TR induction than no Se or SF treatment. Glutathione peroxidase activity was elevated by Se, but not by SF. These data suggest that TR is regulated by Se, as a classic selenoprotein, and by the electrophillic compound SF, while GSH-PX is regulated by Se alone.