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Science Forum Index » Life Extension Forum » Selenium , GPx and TRx toxicity reduced by sulfhydryls
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| Author |
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| Tim |
 Posted: Thu Jan 08, 2004 2:05 pm |
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Guest
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The sodium selenite used in some of these studies is about three times
as toxic as selenium yeast (selenomethionine). Concomitant
supplementation with NAC, lipoic acid may reduced toxicity of high
doses and potentiates it's effects.
A large clinical trial a few years ago using 200mcg of selenium/day
reduced all types of cancer by 45%. This is above RDA and far short of
toxicity (maybe 5000 mcg/day of selenium yeast) but may not have been
optimal.
Biochim Biophys Acta. 2002 Dec 16;1593(1):85-92. Related Articles,
Links
Selenium supplementation acting through the induction of thioredoxin
reductase and glutathione peroxidase protects the human endothelial
cell line EAhy926 from damage by lipid hydroperoxides.
Lewin MH, Arthur JR, Riemersma RA, Nicol F, Walker SW, Millar EM,
Howie AF, Beckett GJ.
University Department of Clinical Biochemistry, The Royal Infirmary,
Lauriston Place, Edinburgh EH3 9YW, UK.
The human endothelial cell line EAhy926 was used to determine the
importance of selenium in preventing oxidative damage induced by
tert-butyl hydroperoxide (tert-BuOOH) or oxidised low density
lipoprotein (LDLox). In cells grown in a low selenium medium,
tert-BuOOH and LDLox killed cells in a dose-dependent manner. At 555
mg/l LDLox or 300 microM tert-BuOOH, >80% of cells were killed after
20 h. No significant cell kill was achieved by these agents if cells
were pre-incubated for 48 h with 40 nM sodium selenite, a
concentration that maximally induced the activities of cytoplasmic
glutathione peroxidase (cyGPX; 5.1-fold), phospholipid hydroperoxide
glutathione peroxidase (PHGPX;1.9-fold) and thioredoxin reductase (TR;
3.1-fold). Selenium-deficient cells pre-treated with 1 microM gold
thioglucose (GTG) (a concentration that inhibited 25% of TR activity
but had no inhibitory effect on cyGPX or PHGPX activity) were
significantly (P<0.05) more susceptible to tert-BuOOH toxicity (LC(50)
110 microM) than selenium-deficient cells (LC(50) 175 microM). This
was also the case for LDLox. In contrast, cells pre-treated with 40 nM
selenite prior to exposure to GTG were significantly more resistant to
damage from tert-BuOOH and LDLox than Se-deficient cells. Treatment
with GTG or selenite had no significant effect on intracellular total
glutathione concentrations. These results suggest that selenium
supplementation, acting through induction of TR and GPX, has the
potential to protect the human endothelium from oxidative damage.
Copyright 2002 Elsevier Science B.V.
PMID: 12431787 [PubMed - indexed for MEDLINE]
selenium metabolism, selenoproteins and mechanisms of cancer
prevention: complexities with thioredoxin reductase.
http://carcin.oupjournals.org/cgi/content/full/20/9/1657
Mechanisms of the regulation of thioredoxin reductase activity in
cancer cells by the chemopreventive agent selenium.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9354464&dopt=Abstract
http://ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3210451&dopt=Abstract
http://ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3924956&dopt=Abstract
Tim |
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