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Description:
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Quercetin (Q ) , a water -soluble flavonoid that is ubiquitous to foods of plant
origin is postulated to protect against colon cancer due to its antioxidant activity . In
contrast , we have shown that a dietary combination of fish oil (FO ; n -3 fatty acids ) and
pectin may protect against colon cancer by decreasing endogenous antioxidant enzyme
activities leading to increased reactive oxygen species (ROS ) , an inducer of apoptosis .
We hypothesized that adding an antioxidant to a FO diet may negate the beneficial
effects of FO by counteracting FO effects on colonocyte redox status . To test this , we
provided 40 rats with FO or CO (fiber = pectin ) diets with Q being 0 or 0 .45 % of the diet
for 10 wk . All rats were injected with azoxymethane (AOM ) on d 21 and 28 .
Measurements included : aberrant crypt (AC ) enumeration (colon cancer marker ) ;
apoptosis (TUNEL assay ) ; catalase (CAT ) , superoxide dismutase (SOD ) , and
glutathione peroxidase (GPx ) activities ; reduced and oxidized glutathione concentrations
(GSH /GSSG ) ; and oxidative DNA damage (8 -OHdG adducts ) . AC numbers were lower
in FO vs CO rats (p <0 .0001 ) , but tended to increase for FO diets containing Q
(P <0 .098 ) . The apoptotic index was higher (p <0 .0001 ) when Q was added to the FO and
CO diets . Total SOD (lipid main effect , p=0 .0136 ) and GPX activity (p=0 .0025 ) was elevated in CO rats . CAT activity was higher (p=0 .0204 ) in FO rats , however Q
diminished this effect . GSH was not affected by diet ; yet , GSSG accumulated
(p=0 .0554 ) in CO rats with Q as compared to CO rats without Q . The GSH /GSSG ratio
was lower (p=0 .0314 ) in CO rats than in FO rats . There was no difference in 8 -OHdG
adduct levels in FO vs CO rats , however , Q decreased 8 -OHdG adducts in CO rats
(p=0 .0428 ) . Despite increasing apoptosis , Q did not significantly lower AC formation .
These data suggest that the distinct effects of the CO /Q and FO /Q combinations are
functioning through different mechanisms to induce apoptosis . The long -term
consequences of adding antioxidants such as Q to a diet thought to exert its anticancer
effect through a pro -oxidant mechanism are unknown and deserve further study . |