The Structural and Pharmacokinetic Properties of Oxidized Human Serum Albumin, Advanced Oxidation Protein Products (AOPP)

• IWAO Yasunori

  Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University

• ANRAKU Makoto

  Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University

• HIRAIKE Mikako

  Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University

• KAWAI Keiichi

  School of Health Sciences, Faculty of Medicine, Kanazawa University

• NAKAJOU Keisuke

  Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University

• KAI Toshiya

  Pharmaceutical Research Center, Nipro Corporation

• SUENAGA Ayaka

  Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University

• OTAGIRI Masaki

  Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University

Abstract

  To determine the pharmacokinetic properties of advanced oxidation protein products (AOPP), we prepared oxidized human serum albumin (oxi-HSA) using chloramine-T (a hypochlorite analogue) in vitro. The AOPP and dityrosine content of oxi-HSA (AOPP content, 244.3±12.3 μM; dityrosine content, 0.7±0.11 nmol of dityrosine/mg protein) were similar to those of uremic patients. In structural analysis, the increases in AOPP and dityrosine content of HSA induced slight decreases in its α-helical content. In pharmacokinetic analysis, oxi-HSA left the circulation rapidly, and organ distribution of oxi-HSA 30 min after intravenous injection was 51% for the liver, 23% for the spleen, and 9% for the kidney, suggesting that the liver and spleen were the main routes of plasma clearance of oxi-HSA. The liver and spleen uptake clearance of oxi-HSA were significantly greater than those of normal HSA (CLliver, 5058±341.6 vs 24±4.2 μL/hr [p<0.01]; CLspleen, 2118±322.1 vs 32±2.7 μL/hr [p<0.01]). However, uptake by other organs was not significantly affected by oxidation. These results suggest that the liver and spleen play important roles in elimination of AOPP.<br>

Journal

• Drug Metabolism and Pharmacokinetics

  Drug Metabolism and Pharmacokinetics 21 (2), 140-146, 2006

  The Japanese Society for the Study of Xenobiotics

Keywords

• human serum albumin
• structural change
• advanced oxidation protein products
• pharmacokinetics

Details

• CRID: 1390001205181418752
• NII Article ID: 10017423219
• NII Book ID: AA1162652X
• DOI: 10.2133/dmpk.21.140
• COI: 1:CAS:528:DC%2BD28Xmt1aku7s%3D
• ISSN: 18800920
• ISSN: 13474367
• PubMed: 16702734
• Web Site: http://api.elsevier.com/content/article/PII:S1347436715306923?httpAccept=text/xml
• Web Site: http://api.elsevier.com/content/article/PII:S1347436715306923?httpAccept=text/plain
• Web Site: https://search.jamas.or.jp/link/ui/2006312853
• Text Lang: en
• Data Source:
  • JaLC
  • Crossref
  • PubMed
  • CiNii Articles
• Abstract License Flag: Disallowed