Arsenic (As) is a ubiquitous metal in the environment and the accumulation of arsenic in ground water and plants poses a health risk to both humans and animals. Arsenic-induced toxicity is associated with increased oxidative stress through regulation of
antioxidative-related enzymes and cell cycle progression. Selenium (Se) is a trace element essential for animal and human growth. Se acts as an antioxidant with anticancer effect and is
a key component in selenoproteins, such as glutathione peroxidase (GPX) family, that incorporate Se as selenocysteine translationally into the amino acid sequence. Se may exert its protective effect on As-induced toxicity through modulations of cell proliferation, cell cycle progression and the activities of antioxidative-related selenoproteins. Se pretreatment as selenite reduced As2O3-induced cytotoxicity through GPX modulation. The As detoxification mechanistic paths involve antioxidative defense system and multidrug resistance transporters. Se was shown to inhibit the growth of drug-resistance cell lines and to prevent the development of drug resistance. However, no available information can be found on the interaction of selenium with multidrug resistance transporters.
Cancer is the leading cause for death in human health and may be prevented through improving physiological antioxidative system by consuming protective compounds or avoiding mutagen exposure. Natural plant extracts have gained much attention recently due to the antioxidative and antimutagenic abilities to defense the dangerous effects caused by toxins or mutagens. The form and the concentration of Se used are critical for cancer prevention. With the knowledge of Se as an anticarcinogenic agent, delivery of this protective element through the food systems is a natural and harmless method to provide enrichment for humans. Since plants with high sulfur content tend to take up high levels of Se, broccoli has been enriched with Se for possible Se supplementation through dietaryconsumption. The addition of Se-enriched broccoli to the rat diets significantly reduced the
mammary and colon tumor incidence.
The primary objective of this proposed study during the first year will aim at theprotective effect of Se-enriched broccoli extract on As-induced toxicity through modulation of the main antioxidative enzymes and cell cycle in primary culture of porcine aortic endothelial cells (PAECs). The activities of cGPX and GST as well as the cell cycle progression will be investigated. The main objective during the second year will aim at the effect of SeB extract on expression of multidrug resistance transporters in PAECs. Distribution of differential transporters in PAECs will be surveyed and the regulation of specific multidrug resistance
transporters expression by Se-enriched broccoli extract will be investigated. The final goal for this proposed study is to investigate the possible mechanism responsible for the protective
effect of SeB extract on As-induced toxicity.
