The structural and pharmacokinetic properties of oxidized human serum albumin, advanced oxidation protein products (AOPP).
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.
Iwao
Yasunori
Y
Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Oe-honmachi, Japan.
Anraku
Makoto
M
Hiraike
Mikako
M
Kawai
Keiichi
K
Nakajou
Keisuke
K
Kai
Toshiya
T
Suenaga
Ayaka
A
Otagiri
Masaki
M
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
D000596:Amino Acids; D001688:Biological Products; D012709:Serum Albumin; D014443:Tyrosine; C007543:dityrosine