title: The structural and pharmacokinetic properties of oxidized human serum albumin, advanced oxidation protein products (AOPP).
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 microM; 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 alpha-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 microL/hr [p<0.01]; CLspleen, 2118+/-322.1 vs 32+/-2.7 microL/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.
authors.affiliation: Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Oe-honmachi, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Iwao
authors.forename: Makoto
authors.initials: M
authors.lastname: Anraku
authors.forename: Mikako
authors.initials: M
authors.lastname: Hiraike
authors.forename: Keiichi
authors.initials: K
authors.lastname: Kawai
authors.forename: Keisuke
authors.initials: K
authors.lastname: Nakajou
authors.forename: Toshiya
authors.initials: T
authors.lastname: Kai
authors.forename: Ayaka
authors.initials: A
authors.lastname: Suenaga
authors.forename: Masaki
authors.initials: M
authors.lastname: Otagiri
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001688:Biological Products / Q000493:pharmacokinetics*; D015153:Blotting, Western; D008297:Male; D051379:Mice; D010084:Oxidation-Reduction; D012709:Serum Albumin / Q000493:pharmacokinetics*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D000596:Amino Acids; D001688:Biological Products; D012709:Serum Albumin; D014443:Tyrosine; C007543:dityrosine