Cooney, Robert V.

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    Inhibition of colonic aberrant crypt formation by the dietary flavonoids (+)-catechin and hesperidin.
    ( 2002) Franke, Adrian A. ; Custer, Laurie J. ; Cooney, Robert V. ; Tanaka, Yuichiro ; Xu, Meirong ; Dashwood, Roderick H.
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    The nitration product 5-nitro-gamma-tocopherol is increased in the Alzheimer brain.
    ( 2002-03) Williamson, Kelly S. ; Gabbita, S Prasad ; Mou, Shenyun ; West, Melinda ; Pye, Quentin N. ; Markesbery, William R. ; Cooney, Robert V. ; Grammas, Paula ; Reimann-Philipp, Ulrich ; Floyd, Robert A. ; Hensley, Kenneth
    Oxidative stress and quasi-inflammatory processes recently have been recognized as contributing factors in the pathogenesis of Alzheimer's disease (AD). Reactive nitrating species have specifically been implicated in AD based on immunochemical and instrumental detection of nitrotyrosine in AD brain protein. The significance of lipid-phase nitration has not been investigated in AD. This study documents a significant two- to threefold increase in the lipid nitration product 5-nitro-gamma-tocopherol in affected regions of the AD brain as determined by high-performance liquid chromatography with electrochemical detection. In a bioassay to compare the relative potency of alpha-tocopherol and gamma-tocopherol against nitrative stress, rat brain mitochondria were exposed to the peroxynitrite-generating compound SIN-1. The oxidation-sensitive Kreb's cycle enzyme alpha-ketoglutarate dehydrogenase was inactivated by SIN-1, in a manner that could be significantly attenuated by gamma-tocopherol (at <10 microM) but not by alpha-tocopherol. These data indicate that nitric oxide-derived species are significant contributors to lipid oxidation in the AD brain. The findings are discussed in reference to the neuroinflammatory hypothesis of AD and the possible role of gamma-tocopherol as a major lipid-phase scavenger of reactive nitrogen species.
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    Bioavailability and antioxidant effects of orange juice components in humans.
    ( 2005-06) Franke, Adrian A. ; Cooney, Robert V. ; Henning, Susanne M. ; Custer, Laurie J.
    Seven healthy females and six males consumed daily 256 mg of vitamin C, 271 mg of flavanones (mainly as glycosides), 6 mg of carotenoids (mainly xanthophylls and cryptoxanthins), and 0.16 mg of folate by incorporation of daily three times 236 mL of not from concentrate orange juice (OJ) into their habitual diet. At the end of 3 weeks, mean vitamin C, folate, carotenoid, and flavanone plasma concentrations increased significantly relative to baseline by 59% (p < 0.001), 46% (p = 0.018), and 22% (p < 0.001), and 8-fold (p = 0.045), respectively. Flavanones were excreted in urine 9-fold more at the end of the intervention (p = 0.01) but returned to baseline 2 days after study completion. After the 3 week intervention, plasma concentrations of vitamins A and E did not change. 8-Hydroxydeoxyguanosine in white blood cells declined by 16% (p = 0.38; n = 11), and in individuals with high baseline concentrations by 29% (p = 0.36; n = 7), respectively. Low-density lipoprotein (LDL)-/high-density lipoprotein (HDL)-cholesterol ratios decreased but cholesterol (HDL, LDL, total) and thiobarbituric acid reactive substance plasma concentrations did not change significantly. We conclude from this pilot study that OJ is an excellent food source to enhance circulating concentrations of valuable hydrophilic as well as lipophilic phytochemicals.
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    Tocopherols and prostate cancer.
    ( 2006-09) Cooney, Robert V.
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    Enhancement of intracellular gamma-tocopherol levels in cytokine-stimulated C3H 10T1/2 fibroblasts: relation to NO synthesis, isoprostane formation, and tocopherol oxidation.
    ( 2007) Tanaka, Yuichiro ; Wood, Leslie A Lesoon ; Cooney, Robert V.
    Stimulation of C3H 10T1/2 murine fibroblasts with interferon-gamma(IFN) and bacterial lipopolysaccharide (LPS) generates reactive oxygen and nitrogen species leading to DNA damage, lipid oxidation, and tocopherol oxidation. The tocopherols possess unique chemical and biological properties that suggest they have important roles related to intracellular defense against radical-mediated damage.