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Submitted on January 10, 2004
Accepted on March 16, 2004
From Departments of Medical Research (C.T.-C, H.-W.C.,), Internal Medicine (W.-D.C., T.-D.W., Y.-T.L.), and Pathology (S.-M.H.), National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei; Formosan Blood Purification Foundation (S.-Y.L.), Taipei; Department of Health (T.-J.C.), Taichung; Department of Biomedical Engineering (Y.-L.C.), Chung-Yuan Christian University, ChungLi, Taiwan.
* To whom correspondence should be addressed. E-mail: ytlee{at}ha.mc.ntu.edu.tw or smhsu{at}ha.mc.ntu.edu.tw.
Objective--The effect of ascorbate treatment on apheresis-induced oxidative stress in uremic and dyslipidemic patients was evaluated.
Methods and Results--We developed a chemiluminescence-emission spectrum and high-performance liquid chromatography analysis to assess the effect of ascorbate supplement on plasma reactive oxygen species (ROS) scavenging activity and oxidized lipid/protein production in hyperlipidemic and uremic patients undergoing apheresis. Apheresis was efficient in reduction of atherogenic lipoproteins, complement, fibrinogen, soluble intercellular adhesion molecule-1, and oxidative parameters including phosphatidylcholine hydroperoxide (PCOOH), malonaldehyde, methylguanidine, and diotyrosine. Apheresis itself, however, activated leukocytes to increase ROS activity and reduced the plasma ROS scavenging activity. Ascorbate administration selectively diminished apheresis-enhanced H2O2 and inflammatory mediators such as tumor necrosis factor alpha (TNF-
) and monocyte chemoattractant protein-1. Chronically dyslipidemic and uremic patients undergoing biweekly apheresis plus ascorbate treatment had lower levels of C-reactive protein and PCOOH than did those without ascorbate treatment during a 6-month follow-up study period.
Conclusions--We demonstrate that apheresis with ascorbate treatment provides a therapeutic potential in reducing atherosclerotic risk via inhibition of H2O2-induced oxidative stress in patients with uremia or dyslipidemia.
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