Quercetin-dependent induction of colonocyte apoptosis depends on the dietary lipid source

A125

We have previously reported that quercetin (Q) added to a diet containing fish oil (FO; n-3 fatty acids) or corn oil (CO; n-6 fatty acids) increases apoptosis in the rat colon. Because Q is an antioxidant we investigated whether the increase in apoptosis was mediated by changes in redox status of rat colonocytes. Therefore, rats (n=40) were fed FO or CO diets supplemented with 0 or 0.45% Q for 10 wk. All rats were injected with azoxymethane on d 21 and 28. At termination, colonocytes from scraped mucosa were lysed and stored at -80°C. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activity (indicators of endogenous antioxidant capacity) were measured by ELISA. The levels of reduced and oxidized glutathione (GSH/GSSG) were measured by HPLC in colon mucosal scrapings. There was no effect of treatment on the activity of mitochondrial SOD. However, total SOD was elevated (p=0.0206) in the CO rats, with the greatest difference occurring between CO and FO rats without Q in the diet. In addition, GPx was elevated (P = 0.0025) in CO rats. CAT was higher (p=0.0204) in FO rats, which was primarily due to the elevated CAT in FO rats without Q in the diet. GSH level was not affected by diet; however, GSSG was elevated (P = 0.0554) in CO rats compared to FO rats supplemented with Q. The GSH/GSSG ratio was lower (P = 0.0314) in CO rats than in FO rats. These data suggest that the redox environment in CO/Q colonocytes enhanced oxidative stress, which may contribute to an increase in apoptosis. In contrast, the pro-apoptotic FO and Q diet appears to be operating through a different mechanism. Funding: USDA-CSREES 2005-34402-16401, and NIEHS P30-ES09106.