Oxidative stress induced by iron released from transferrin in low pH peritoneal dialysis solution.
BACKGROUND
Transferrin binds extracellular iron and protects tissues from iron-induced oxidative stress. The binding of iron and transferrin is pH dependent and conventional peritoneal dialysis (PD) solutions have unphysiologically low pH values. Herein, we investigated whether conventional PD solution releases iron from transferrin and if the released iron causes oxidative stress.


METHODS
Effects of PD solutions on iron binding to transferrin were examined with purified human transferrin and transferrin in dialysates drained from PD patients. Oxidative stress induced by iron released from transferrin was evaluated in terms of the formation of thiobarbituric acid reactive substance (TBARS) and protein carbonylation in the human red blood cell (RBC) membrane. The iron deposition in peritoneal tissue from PD patients was evaluated by Perls' staining with diaminobenzidine intensification.


RESULTS
Low pH PD solution released iron from transferrin. This iron release occurred within 1 min. Iron release was not observed in neutralized PD solution. Iron released from transferrin in low pH PD solution increased TBARS formation and protein carbonylation in the human RBC membrane. Iron deposition, which is prominent in the fibrotic area facing the peritoneal cavity, was observed in the peritoneum of PD patients.


CONCLUSIONS
Iron released from transferrin in low pH PD solution can produce oxidative stress in the peritoneum of a PD patient. Neutralizing PD solution can avoid this problem. Iron deposition in the peritoneum may participate in the pathogenesis of peritoneal fibrosis in PD patients.
Yamaji
Yasuyoshi
Y
Kidney Disease Center and Internal Medicine, Saitama Social Insurance Hospital, 4-9-3 Kitaurawa, Urawa-ku, Saitama-City, Saitama, 330-0074, Japan. yamaji@1985.jukuin.keio.ac.jp
Nakazato
Yuichi
Y
Oshima
Naoki
N
Hayashi
Matsuhiko
M
Saruta
Takao
T
D015314:Dialysis Solutions / Q000737:chemistry*; D004910:Erythrocyte Membrane / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007501:Iron / Q000378:metabolism*; D008563:Membrane Lipids / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D018384:Oxidative Stress; D010530:Peritoneal Dialysis; D010537:Peritoneum / Q000378:metabolism; D011522:Protons; D013194:Staining and Labeling; D014168:Transferrin / Q000378:metabolism*
D015314:Dialysis Solutions; D008563:Membrane Lipids; D008565:Membrane Proteins; D011522:Protons; D014168:Transferrin; D007501:Iron