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- W200318145 abstract "Recent experimental data suggest that cotreatment with reduced lipoic acid can ameliorate nitrate tolerance, a process that involves oxidative inhibition of the bioactivating enzyme, the mitochondrial aldehyde dehydrogenase (ALDH-2). We sought to determine whether this applies to humans. 8 Healthy male volunteers were assigned to take a single dose of glycerol trinitrate (GTN, 0.8mg), pentaerithrityl tetranitrate (PETN, 80mg) or GTN plus pretreatment of alpha-lipoic acid (LA, 600mg, 30min in advance). After maximum plasma-concentrations were reached (30min for GTN and GTN-LA, 120min for PETN), venous blood was sampled. We assessed the antioxidative capacity of serum by a fluorescence assay, monocyte ALDH-2 activity and biotransformation of a trinitrate-chromophore by HPLC methods. As compared to controls, GTN resulted in a 60% decrease in monocytic ALDH-2 activity (that could be partially restored ex vivo by dithiothreitol) and 30% reduction of nitrate bioactivation as well as a 25% decrease in antioxidative capacity of serum. These effects were significantly improved by pretreatment with LA. Treatment with PETN did not impair ALDH-2 activity, nitrate bioactivation or serum antioxidative capacity. We conclude that treatment with a single dose of GTN but not PETN acutely inhibits ALDH-2 acitivity and nitrate bioactivation in human volunteers. The GTN effects could be ameliorated by LA pretreatment." @default.
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- W200318145 date "2008-03-01" @default.
- W200318145 modified "2023-09-26" @default.
- W200318145 title "Monitoring development and prevention of nitrate tolerance (tachyphylaxis) in healthy volunteers with monocytic ALDH‐2 activity as a marker" @default.
- W200318145 doi "https://doi.org/10.1096/fasebj.22.1_supplement.1129.1" @default.
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