Hydralazine: a potent inhibitor of aldehyde oxidase activity in vitro and in vivo |
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Authors: | C Johnson C Stubley-Beedham J G Stell |
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Affiliation: | 1. Department of Molecular Genetic Diagnostics and Cell Biology, Division of Laboratory Medicine, Institute of Pediatrics, Research Center for Children''s Health, 119991, Moscow, Russia;2. Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, Moscow, 125315, Russia;3. Department of Biophysics, Biological Faculty, Moscow State University, Moscow, 119991, Russia;4. Institute for Atherosclerosis Research, Skolkovo Innovative Center, Moscow, 121609, Russia;5. National Research Center for Preventive Medicine, Moscow, 101000, Russia;6. Faculty of Medicine, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia;7. School of Medicine, University of Western Sydney, Campbelltown, NSW 2560, Australia |
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Abstract: | The interaction of the vasodilator, hydralazine, with the molybdenum hydroxylases, aldehyde oxidase and xanthine oxidase has been investigated. A potent progressive inhibition of rabbit liver aldehyde oxidase, in the presence of substrate, by low concentrations of hydralazine (0.1-1 microM) was observed in vitro but no effect was seen with bovine milk xanthine oxidase. This activity was mirrored in vivo when levels of aldehyde oxidase were significantly decreased in rabbits administered hydralazine (10 mg/kg/day for seven days) whereas hepatic xanthine oxidase activity was unaltered by hydralazine treatment. Various metabolites of hydralazine were synthesized but found to be devoid of in vitro inhibitory activity. Aldehyde oxidase prepared from either guinea pig or baboon liver was inhibited in a similar way to that of rabbit liver. |
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