Browsing by Subject "glutathione"
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Item Effects of dietary fat and fiber on the oxidative status of the small intestine and colon of rats(Texas A&M University, 2006-08-16) Sanders, Lisa MerleColon cancer is one of the most commonly diagnosed cancers in the US, yet small intestine cancer is a rare event. While there are many similarities between these two tissues, inherent differences such as redox status, may contribute to the variation in cancer occurrence. We examined the difference in reactive oxygen species (ROS) generation, antioxidant enzyme activity and oxidative DNA damage in the small and large intestine of rats under normal conditions and following exposure to exogenous oxidative stress. Basal ROS and antioxidant enzyme activities were greater in the colon than the small intestine, and the balance of ROS to antioxidant enzymes in the colon was more pro-oxidant than in the small intestine. During oxidative stress, ROS and oxidative DNA damage were greater in the colon than the small intestine. Thus the colon responds to oxidative stress less effectively than the small intestine, possibly contributing to increased cancer incidence at this site. We next wanted to understand how diets containing a combination of fish or corn oil and pectin or cellulose may alter the redox environment of the colon. ROS, oxidative DNA damage, antioxidant enzyme activity and apoptosis were measured in colonocytes of rats fed one of four diets containing either corn oil or fish oil and cellulose or pectin. Measurements were madein rats untreated with carcinogen and rats exposed to a chemical carcinogen and radiation. In rats not treated with a carcinogen, fish oil enhanced ROS, and fish oil/pectin suppressed antioxidant enzymes as compared to corn oil/cellulose. Oxidative DNA damage was inversely related to ROS in the fish oil/pectin diet and apoptosis was enhanced relative to other diets. In carcinogen treated and irradiated rats, a similar protective effect was seen with fish oil/pectin as evidenced by a reduction in oxidative DNA damage and enhancement of apoptosis. This suggests that a diet containing fish oil/pectin may protect against colon carcinogenesis by modulation of the redox environment to promote apoptosis and minimize oxidative DNA damage.Item The Pro-Antioxidant Role of Zinc Supplementation in Cadmium-Treated Choroid Plexus(2014-05-06) Francis Stuart, Samantha D.Cadmium (Cd) is a toxic heavy metal with no known physiological function in higher order animals. Previous studies in primary cultures of neonatal rat choroid plexus (CP) epithelial cells indicated Cd induced oxidative stress and stimulated apical choline transport, and suggested zinc (Zn) supplementation might abate both oxidative stress and modulation of transport. The objective of this thesis was to elucidate how Zn, a nutritive mineral normally accumulated by CP, attenuated oxidative stress. I hypothesize that Zn, which can function as a pro-antioxidant, abates Cd-induced oxidative stress either by induction of metallothionein-1 (MT-1) or enhancement of glutathione (GSH) biochemistry. Thus, in primary cultures of neonatal rat CP epithelial cells, I characterized the effects of sub-micromolar Cd and efficacy of Zn supplementation to attenuate Cd-induced cellular and oxidative stress without or with manipulation of GSH synthesis. To characterize the Cd-induced stress response, CP epithelial cells were treated with 0 or 500 nM CdCl_(2) in serum-free medium (SFM) for 12 h; samples were collected at 3, 6, 9, and 12 h. Induction of heme oxygenase-1 (HO-1), heat-shock protein 70 (HSP70), and metallothionein-1 (MT-1) in Cd-treated cells was compared to time-matched controls by immunoblot and qRT-PCR analyses. Cd induced the catalytic and modifier subunits of glutamate-cysteine ligase (GCL), the rate-limiting enzyme in GSH synthesis. To elucidate the effects Zn supplementation in Cd-treated cells depleted of GSH, cells were supplemented for 48 h with 0 or 25 ?M ZnCl_(2) alone or with 100 ?M buthionine sulfoximine (BSO), an inhibitor of GCL, before treatment with 0 or 500 nM CdCl_(2) ? 100 ?M BSO ? 10?M ZnCl_(2) in SFM for 12 h. By luminescence assay, intracellular GSH and oxidized glutathione (GSSG) concentrations were measured. Cd increased intracellular GSH and GSSG, but markedly decreased GSH:GSSG ratio. Inhibition of GSH synthesis exacerbated Cd-induced stress. However, Zn supplementation attenuated the stress response irrespective of BSO treatment, as per decreased induction of HSP70. These data indicate that CP adapts to low-dose Cd by up-regulation of stress proteins and GSH synthesis. Zinc supplementation also may attenuate Cd-induced cellular and oxidative stress, but cytoprotection is independent of GSH status.