Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2004: ¥2,400,000 (Direct Cost: ¥2,400,000)
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Research Abstract |
Dioxins cause various toxicological effects through transformation of the aryl hydrocarbon receptor (AhR). Since dioxins invade the body mainly with diet, it is important to search for dietary antagonists of the AhR. Purpose of this research is search for food that is able to suppress AhR transformation and investigate its biological availability. After screening about 50 food or its extracts, green and black teas, cocoa, milk, molokhia (Egyptian spinach), carrot, and propolis were effectively suppressed 2,3,7,8-tetrachrolodibenzo-p-dioxin (TCDD)-induced AhR transformation in the cell-free experiment. Moreover, over 75% extracts also showed the suppressive effects among 426 extracts from plants. When effective food extracts were applied to the second screening test using Hapa-1c1c7, Hep G2, and Caco-2 cells, these food extracts were also effective. Results from in vivo study demonstrated that oral administration of tea, molokhia, and cacao suppressed AhR transformation in the liver of 3
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-methylcholanthrene (MC)-dosed rats. Regarding the effective components in food, flavonoid showed its structure-activity relationships : Flavone and flavonol had a strong suppressive effect against TCDD-induced AhR transformation, flavanone and catechin had a moderate, and anthocyan and isoflavone had no effect. In addition, lutein, theaflavin, and chlorophylls were isolated and identified as the novel antagonists for the AhR from tealeaves. Expression of cytochrome P4501A1, whichi is a downstream event of AhR transformation, is deeply involved in the toxicity of certain heterocyclicamines including Trp-P-1. Results form in vivo studies clearly demonstrated that tea, molokhia, and cacao suppressed MC-induced expression of cytochrome P4501A1. Independently to this, Trp-P-1 generated active oxygen species and caused DNA damage. Antioxidants in food were suppressed this DNA damage. In conclusion, plant foods and their components may prevent the dioxin toxicity through suppress AhR transformation. Less
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