Project Number: 1950-51000-065-07
Project Type: Specific Cooperative Agreement

Start Date: Oct 01, 2006
End Date: Sep 30, 2011

Objective:
ANTIOXIDANTS RESEARCH LAB To determine if flavonoids are bioavailable as aglycones and glycosides and both parent compounds and their metabolites act in vitro and in vivo as antioxidants. To determine molecular and biochemical mechanisms of flavonoids and their interactions within the antioxidant defense network.

Approach:
1(A)Weanling rats will be divided into groups fed vitamin E replete, depleted or supplemented diets with or without different doses of quercetin. Blood and tissues will be obtained at intervals over 14 wk for analysis of antioxidant status and metabolism and biomarkers of oxidative stress. (B)Hamsters fed extracts of oat bran, almond skin, or bilberry and their blood/tissue collected to determine flavonoid pharmacokinetics and distribution and antioxidant actions. Randomized clinical trials with a cross-over design in healthy older adults will test the bioavailability and antioxidant capacity of these same plant extracts. (C)A pilot clinical trial will test the adequacy of dose and formulation of a manufactured beverage containing catechins and/or N-acetylcysteine. 2(A)Human LDL will be incubated with different flavonoids alone or in combination with other antioxidants to determine their impact on the resistance of nLDL and LDL to oxidation induced by various radical generators. (B)A hemochromatosis mouse model will be used to test the preventive actions of the green tea flavonoid. (C)The effect of bilberry anthocyanins alone or together with xanthophyll carotenoids will be tested in humans for their uptake and metabolism in retina cells and subsequent action on biomarkers of oxidative stress and apoptosis following challenges with hydrogen peroxide or glucose. The impact of anthocyanins on the expression of stress and apoptosis-related proteins and genes will be investigated utilizing mRNA expression gels and GeneChip arrays.