MolPharm xPharm- The Comprehensive Pharmacology Reference

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Jiang, J.
Right arrow Articles by Mason, R. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jiang, J.
Right arrow Articles by Mason, R. P.

Vol. 52, Issue 6, 1081-1086, 1997

In Vivo Production of Nitric Oxide in Rats after Administration of Hydroxyurea

Jinjie Jiang, Sandra J. Jordan, David P. Barr, Michael R. Gunther, Hiroshi Maeda, and Ronald P. Mason

Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709 (J.J., S.J.J., D.P.B., M.R.G., R.P.M.) and Department of Microbiology, Kumamoto University of Medicine, Kumamoto 860, Japan (H.M.).

The metabolism of nitrovasodilators such as glyceryl trinitrate and nitroprusside provides the active moiety of these drugs (that is, nitric oxide). This process is not limited to the known nitrovasodilators, but also occurs with nitroaromatic antimicrobials. Here we report that the administration of hydroxyurea, an antitumor drug, to rats at pharmacological doses formed detectable nitrosyl hemoglobin, which increased with dose. At higher doses, nitrosyl hemoprotein complexes could also be detected in liver tissue. [15N]hydroxyurea was synthesized and compared with [14N]hydroxyurea. These observations verified that nitric oxide detected as nitrosyl hemoglobin or nitrosyl hemoprotein complexes in rats was the result of the metabolism of hydroxyurea. The time course and dose-dependence of nitric oxide generation were also investigated. Hydroxyurea's antineoplastic activity is caused by its direct action on ribonucleotide reductase, the rate-limiting enzyme in DNA synthesis. Because nitric oxide also inhibits ribonucleotide reductase, this metabolite may supplement this action of hydroxyurea. In addition, the known ability of hydroxyurea to ease the pain of sickle cell anemia patients may be the result of vasodilation by the drug-derived nitric oxide.

Copyright © 1997 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 Clin. Cancer Res.Home page
D. Yin, X. Wang, B. M. Konda, J. M. Ong, J. Hu, M. R. Sacapano, M. K. Ko, A. J. Espinoza, D. K. Irvin, Y. Shu, et al.
Increase in Brain Tumor Permeability in Glioma-Bearing Rats with Nitric Oxide Donors
Clin. Cancer Res., June 15, 2008; 14(12): 4002 - 4009.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
V. P. Cokic, B. B. Beleslin-Cokic, M. Tomic, S. S. Stojilkovic, C. T. Noguchi, and A. N. Schechter
Hydroxyurea induces the eNOS-cGMP pathway in endothelial cells
Blood, July 1, 2006; 108(1): 184 - 191.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
M. J. Burkitt and A. Raafat
Nitric oxide generation from hydroxyurea: significance and implications for leukemogenesis in the management of myeloproliferative disorders
Blood, March 15, 2006; 107(6): 2219 - 2222.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
D. C. Tang, J. Zhu, W. Liu, K. Chin, J. Sun, L. Chen, J. A. Hanover, and G. P. Rodgers
The hydroxyurea-induced small GTP-binding protein SAR modulates {gamma}-globin gene expression in human erythroid cells
Blood, November 1, 2005; 106(9): 3256 - 3263.
[Abstract] [Full Text] [PDF]

Home page
 J. Bacteriol.Home page
G. S. Timmins, S. Master, F. Rusnak, and V. Deretic
Requirements for Nitric Oxide Generation from Isoniazid Activation In Vitro and Inhibition of Mycobacterial Respiration In Vivo
J. Bacteriol., August 15, 2004; 186(16): 5427 - 5431.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
G. S. Timmins, S. Master, F. Rusnak, and V. Deretic
Nitric Oxide Generated from Isoniazid Activation by KatG: Source of Nitric Oxide and Activity against Mycobacterium tuberculosis
Antimicrob. Agents Chemother., August 1, 2004; 48(8): 3006 - 3009.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
X. Xu, V. L. Lockamy, K. Chen, Z. Huang, H. Shields, S. B. King, S. K. Ballas, J. S. Nichols, M. T. Gladwin, C. T. Noguchi, et al.
Effects of Iron Nitrosylation on Sickle Cell Hemoglobin Solubility
J. Biol. Chem., September 20, 2002; 277(39): 36787 - 36792.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K. Tsuchiya, M. Yoshizumi, H. Houchi, and R. P. Mason
Nitric Oxide-forming Reaction between the Iron-N-Methyl-D-glucamine Dithiocarbamate Complex and Nitrite
J. Biol. Chem., January 21, 2000; 275(3): 1551 - 1556.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
R. E. Glover, E. D. Ivy, E. P. Orringer, H. Maeda, and R. P. Mason
Detection of Nitrosyl Hemoglobin in Venous Blood in the Treatment of Sickle Cell Anemia with Hydroxyurea
Mol. Pharmacol., June 1, 1999; 55(6): 1006 - 1010.
[Abstract] [Full Text]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1997 by the American Society for Pharmacology and Experimental Therapeutics