Selenium homeostasis and induction of thioredoxin reductase during long term selenite supplementation in the rat.
Selenium is a candidate treatment for liver tumour prevention in chronic liver disease. In this study, we have studied selenium uptake, distribution and accumulation in rats provided with water containing tumour-preventive doses of sodium selenite for 10 weeks. Male Fischer 344 rats were given drinking water containing 1 μg/mL or 5 μg/mL sodium selenite. Selenium levels were monitored in serum and liver tissue over the 10-week period, and the kinetics of induction of the redox-active cytosolic selenoenzyme thioredoxin reductase were followed. Selenite exposure via drinking water caused a dose-dependent increase in blood and liver selenium levels, with plateaus at 6 and 8 weeks, respectively. These plateaus were reached at the same level of selenium regardless of dose, and no further accumulation was observed. A selenium-dependent increase in the activity of TrxR1 in parallel with the increase in liver selenium levels was also seen, and the induction of TrxR1 mRNA was seen only during the first three days of treatment, when the levels of selenium in the liver were increasing. Sodium selenite at 1 and 5 μg/mL did not affect body weight or relative liver mass. We concluded that long-term treatment with selenite did not cause accumulation of selenium and that the activity of TrxR1 in the liver rose with the selenium levels. We therefore suggest that sodium selenite at doses up to 5 μg/mL could be used for long-term tumour prevention.
Division of Pathology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
Suvd
S
Erkhembayar
Annelie
A
Mollbrink
Malin
M
Eriksson
Erik H
EH
Larsen
Lennart C
LC
Eriksson
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D019587:Dietary Supplements; D004790:Enzyme Induction / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D012643:Selenium / Q000097:blood / Q000494:pharmacology*; D013880:Thioredoxin-Disulfide Reductase / Q000096:biosynthesis* / Q000235:genetics; D013997:Time Factors
D012333:RNA, Messenger; D013880:Thioredoxin-Disulfide Reductase; D012643:Selenium