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Document Type:Latin Dissertation
Language of Document:English
Record Number:53843
Doc. No:TL23797
Call number:‭NR50977‬
Main Entry:Johanne Poirier
Title & Author:An investigation into the mechanisms of the hypocholesterolemic effect of selenium in the Syrian hamsterJohanne Poirier
College:McGill University (Canada)
Date:2008
Degree:Ph.D.
student score:2008
Page No:250
Abstract:Supplementation of selenium (Se) has been shown to have important hypocholesterolemic properties in animal experiments and in some human trials; however, underlying mechanisms remain unclear. One possible mechanism may be via the liver X receptor (LXR) pathway that lowers intestinal cholesterol absorption and enhances cholesterol conversion into bile acids. The present thesis studied the effect of Se on LXR ligands (oxysterols) and mRNA abundance of LXR responsive genes, ATP-binding cassette proteins G5 and G8 ( abcg5 , abcg8 ), and Nieman-Pick C1-Like 1 protein (npc1/1 ) in hepatic and jejunal tissues in the Syrian hamster. The first study demonstrated that: (a) hepatic oxysterol concentrations are increased, and plasma cholesterol decreased in hamsters fed supplemental Se; (b) 27-hydroxycholesterol (27-OHC) concentrations are increased in HepG2 cells treated with Se at physiological concentrations in a dose response manner. The second study provided Syrian hamsters supplemental Se in a dose response manner to ascertain if Se: (a) increases hepatic oxysterols through upregulation of specific hepatic P450 enzyme activity and abundance; and (b) decreases plasma and hepatic lipids through LXR pathway upregulation of hepatic abcg5 and abcg8 and increased cholesterol secretion into bile. Se lowered plasma LDL-C concentrations and increased hepatic 27-OHC concentrations without effect on specific P450 enzymes, hepatic cholesterol concentrations or hmgcr . Se upregulated hepatic ldlr and abcg8 without affecting abcg5 or cholesterol and bile acid levels in gallbladder bile. The third study looked at the response of the jejunum to dose response Se supplementation in Syrian hamsters in terms of jejunal abcg5, abcg8, ldlr, hmgcr and npc1/1 . Similar to liver, Se treatment was associated with increased abcg8 without showing an effect on abcg5 . Jejunal npc1/1 was upregulated with Se treatment suggesting that Se might have diminished enterocyte cholesterol levels via its effect on increasing abcg8 . As with gallbladder bile, Se did not increase fecal cholesterol concentrations or bile acids. In conclusion, although Se upregulates the hepatic concentrations of oxysterols and increases abundance of hepatic and jejunal abcg8 , ldlr and jejunal npc1/1 , the hypocholesterolemic effect of Se does not appear to involve the LXR pathway.
Subject:Health and environmental sciences; Hypocholesterolemic; Selenium; Nutrition; 0570:Nutrition
Added Entry:McGill University (Canada)