Effect of Dexrazoxane on Homocysteine-Induced Endothelial Dysfunction in Normal Subjects
Abstract
Objective — Dexrazoxane is an antioxidant prodrug that on hydrolysis is converted into an intracellular iron chelator. We hypothesized that the antioxidant effects of dexrazoxane would prevent homocysteine-induced endothelial dysfunction in the brachial artery of normal human subjects. Methods and Results — Ten healthy volunteers completed a randomized, double-blind, crossover study. Plasma homocysteine levels and brachial artery endothelium-dependent (flow-mediated dilation [FMD]) and endothelium-independent (sublingual nitroglycerin) responses were measured before and 4 hours after ingestion of l -methionine (100 mg/kg), preceded by intravenous administration of dexrazoxane (500 mg/m 2 ) or placebo over 30 minutes. After placebo, oral methionine increased plasma homocysteine (from 5.1±0.4 μmol/L at baseline to 14.2±1.3 μmol/L at 4 hours, P <0.001) and decreased FMD (from 3.8±0.7% at baseline to 1.2±0.5% at 4 hours, P =0.02). Dexrazoxane did not change homocysteine concentrations after methionine administration (14.9±1.1 μmol/L at 4 hours, P =0.29 versus placebo) but did completely abrogate the homocysteine-induced reduction in FMD (from 3.5±0.5% at baseline to 5.9±1.1% at 4 hours, P <0.01 versus placebo). Endothelium-independent responses to sublingual nitroglycerin did not differ after the administration of placebo and dexrazoxane. Conclusions — Administration of the novel antioxidant agent dexrazoxane prevents homocysteine-induced impairment of vascular endothelial function in the brachial artery of healthy subjects.
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The adverse vascular effects of homocysteine (in inhibiting flow-mediated dilatation) are iron-dependent.
“the well-known adverse vascular effects of homocysteine (in inhibiting flow-mediated dilatation) are in fact iron-dependent [701-703]”
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Self-citation
- Authors
- Zheng, H., Dimayuga, C., Hudaihed, A., & Katz, S. D.
- Affiliations
- Peking Union Medical College Hospital (CN)
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 2002-07
- Volume
- 22
- Issue
- 7
- Pages
- E15-8
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- OpenAlex
- W2060348573
- Cited by
- 33
- References
- 34
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2022: 1 · 2021: 1 · 2018: 1 · 2016: 1 · 2015: 1 · 2013: 1 · 2012: 2
- FWCI
- 1.98
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01hl051433-09)
- National Heart, Lung, and Blood Institute (HL-R01-51433, K24HL004024, HL K-24-04024)
- National Center for Research Resources (M01RR000645)
- Topics
- Health Sciences › Medicine › Rheumatology › Folate and B Vitamins Research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Keywords
- dexrazoxane, homocysteine, endothelial dysfunction, flow-mediated dilation, brachial artery, methionine, iron chelation, antioxidants, nitroglycerin response, vascular function
- MeSH terms
- Adult, Antioxidants, Blood Flow Velocity, Brachial Artery, Cardiovascular Agents, Chelating Agents, Endothelium, Vascular, Female, Homocysteine, Humans, Iron, Male, Methionine, Razoxane, Oxidative Stress, Cross-Over Studies
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