Document Detail


Development of polyethylene glycol-conjugated poly-S-nitrosated serum albumin, a novel S-Nitrosothiol for prolonged delivery of nitric oxide in the blood circulation in vivo.
MedLine Citation:
PMID:  15901798     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
S-Nitrosothiols are an interesting class of nitric oxide (NO) donors used for the treatment of circulation disorders. In this study, we developed a novel macromolecular NO donor in which 10 NO molecules were covalently bound to polyethylene glycol (PEG)-conjugated bovine serum albumin (BSA) through S-nitrosothiol linkages (PEG-poly SNO-BSA). Intermolecular disulfide linkages possibly formed during the introduction of thiol groups to BSA were prevented in PEG-poly SNO-BSA. Electron spin resonance study indicated that PEG-poly SNO-BSA does release the NO radical in the blood circulation in vivo. The area under the concentration-time curve of (111)In-PEG-poly N-succinimidyl S-acetylthioacetate (SATA)-BSA, the carrier part of PEG-poly SNO-BSA, was 1.7 times greater than that of (111)In-BSA after intravenous injection in mice. After intravenous injection in rats at an equivalent NO dose (3 micromol of NO per kilogram), the duration of reduction in the blood pressure was 2.3 to 3.7 times longer in PEG-poly SNO-BSA than in classic S-nitrosothiols such as S-nitroso-N-acetyl penicillamine, S-nitrosoglutathione, and NO-BSA. The release half-life of NO from PEG-poly SNO-BSA was 11 to 108 times longer than those of the classic S-nitrosothiols examined, and this slow release rate of NO would explain the sustained reduction in the blood pressure after intravenous injection of PEG-poly SNO-BSA in rats. No cross-tolerance between PEG-poly SNO-BSA and nitroglycerin was also observed. These findings indicate that the novel S-nitrosothiol PEG-poly SNO-BSA is a promising compound that exhibits unique characteristics of sustained release of NO in the blood circulation in vivo, which would be beneficial for the treatment of circulation disorders.
Authors:
Hidemasa Katsumi; Makiya Nishikawa; Fumiyoshi Yamashita; Mitsuru Hashida
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-05-18
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  314     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  2005 Sep 
Date Detail:
Created Date:  2005-08-22     Completed Date:  2005-10-21     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1117-24     Citation Subset:  IM    
Affiliation:
Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Pressure / drug effects
Drug Delivery Systems*
Free Radicals
Male
Mice
Nitric Oxide / blood*
Nitric Oxide Donors / pharmacology*
Nitrites / blood
Nitroglycerin / pharmacology
Nitrosation
Polyethylene Glycols / administration & dosage*
Rats
Rats, Sprague-Dawley
Serum Albumin, Bovine / administration & dosage*
Vasodilation / drug effects
Chemical
Reg. No./Substance:
0/Free Radicals; 0/Nitric Oxide Donors; 0/Nitrites; 0/Polyethylene Glycols; 0/Serum Albumin, Bovine; 10102-43-9/Nitric Oxide; 55-63-0/Nitroglycerin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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