The structural and pharmacokinetic properties of oxidized human serum albumin, advanced oxidation protein products (AOPP)
The structural and pharmacokinetic properties of oxidized human serum albumin, advanced oxidation protein products (AOPP)
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DOI：
10.2133/dmpk.21.140
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发表时间：
2006-01-01
影响因子：
2.1
通讯作者：
Otagiri, Masaki
中科院分区：
文献类型：
--
作者：
Iwao, Yasunori;Anraku, Makoto;Otagiri, Masaki
为了研究晚期氧化蛋白产物（AOPP）的药代动力学特性，我们在体外用氯胺-T（次氯酸盐类似物）制备了氧化人血清白蛋白（oxi-HSA）。oxi-HSA的AOPP和二酪氨酸含量（AOPP含量，244.3 +/- 12.3 μ M;二酪氨酸含量，0.7 +/- 0.11 nmol二酪氨酸/mg蛋白质）与尿毒症患者相似。在结构分析中，HSA的AOPP和二酪氨酸含量的增加引起其α-螺旋含量的轻微降低。在药代动力学分析中，oxi-HSA迅速离开循环，静脉注射后30 min oxi-HSA的器官分布为肝脏51%，脾脏23%，肾脏9%，表明肝脏和脾脏是oxi-HSA的主要血浆清除途径。oxi-HSA的肝和脾摄取清除率显著大于正常HSA的摄取清除率（CL肝，5058 +/- 341.6 vs 24 +/- 4.2 μ L/hr [p < 0.01]; CL脾，2118 +/- 322.1 vs 32 +/- 2.7 μ L/hr [p < 0.01]）。然而，其他器官的吸收并没有受到氧化的显著影响。提示肝、脾在AOPP的清除中起重要作用。
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 mu M; 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 mu L/hr [p < 0.01]; CLspleen, 2118 +/- 322.1 vs 32 +/- 2.7 mu L/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.