Abstract |
Thioredoxin-1 (Trx) is a redox-active protein with anti-inflammatory effects. The effect of albumin fusion on the pharmacokinetic and pharmacodynamic properties of Trx was evaluated in this study. The findings indicate that the properties of human serum albumin and the fusion protein are comparable. The fusion protein showed similar plasma concentration and organ distribution profiles as human serum albumin. The fusion protein accumulated in lungs, reaching levels higher than Trx. In an insulin reducing assay, the activity of the fusion protein was 60% of the activity of Trx. However, survival rate of endotoxic shock mice induced by the administration of a lipopolysaccharide and D- galactosamine for fusion protein was double that of Trx. The findings reported herein indicate that the fusion protein is likely to have great clinical applications in areas such as the treatment of reperfusion injuries.
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Authors | Shotaro Ikuta, Victor Tuan Giam Chuang, Yu Ishima, Keisuke Nakajou, Masato Furukawa, Hiroshi Watanabe, Toru Maruyama, Masaki Otagiri |
Journal | Journal of controlled release : official journal of the Controlled Release Society
(J Control Release)
Vol. 147
Issue 1
Pg. 17-23
(Oct 01 2010)
ISSN: 1873-4995 [Electronic] Netherlands |
PMID | 20678999
(Publication Type: Journal Article)
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Copyright | Copyright © 2010. Published by Elsevier B.V. All rights reserved. |
Chemical References |
- Anti-Inflammatory Agents, Non-Steroidal
- Recombinant Fusion Proteins
- Serum Albumin
- Thioredoxins
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Topics |
- Animals
- Anti-Inflammatory Agents, Non-Steroidal
(chemistry, pharmacokinetics, therapeutic use)
- Blotting, Western
- Circular Dichroism
- Disease Models, Animal
- Drug Stability
- Electrophoresis, Polyacrylamide Gel
- Enzyme-Linked Immunosorbent Assay
- Humans
- Male
- Mice
- Mice, Inbred Strains
- Pichia
(genetics)
- Protein Conformation
- Recombinant Fusion Proteins
(chemistry, pharmacokinetics, therapeutic use)
- Serum Albumin
(chemistry, genetics)
- Shock, Septic
(drug therapy)
- Survival Analysis
- Thioredoxins
(administration & dosage, pharmacokinetics, therapeutic use)
- Tissue Distribution
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