Intravenous iron administration induces oxidation of serum albumin in hemodialysis patients.
BACKGROUND
Intravenous iron administration (IVIR) is effective for correcting anemia in hemodialysis (HD) patients. However, it may also enhance the generation of hydroxyl radicals. Recently, plasma proteins have been demonstrated to be extremely susceptible to oxidative stress. Therefore, we investigated the effect of IVIR on the oxidative status of albumin, a major plasma protein, in HD patients.


METHODS
Eleven hemodialysis (HD) patients were treated with 40 mg of saccharated ferric oxide intravenously after every dialysis session for four weeks, and 11 age-/gender-matched HD patients were treated with vehicle. We performed high performance liquid chromatography (HPLC) analysis of serum albumin and determined the levels of reduced and oxidized albumin. Carbonyl formation of plasma proteins were also measured using an anti-2,4 dinitrophenylhydrazine antibody in patients with or without IVIR.


RESULTS
IVIR resulted in an increase in both disulfide form (f(HNA-1)) and oxidized form (f(HNA-2)) of albumin in HD patients (36.0 +/- 6.03 vs. 41.7 +/- 6.27; 5.46 +/- 1.50 vs. 8.7 +/- 2.22, respectively, P < 0.05). The findings here also show that IVIR substantially increased plasma protein carbonyl content by oxidizing albumin. In addition, we found a strong correlation between plasma carbonyl content and the levels of oxidized albumin (f(HNA-1) and f(HNA-2)) in HD patients (R= 0.674 and R= 0.724, respectively, P < 0.01).


CONCLUSIONS
The results of this study indicate that the HPLC analysis of serum albumin represents a potentially useful method for the quantitative and qualitative evaluation of oxidative stress in HD patients, and strongly suggest the possibility that oxidative stress, generated by IVIR, enhances the oxidation of albumin in those patients.
Anraku
Makoto
M
Department of Biopharmaceutics and Department of Nephrology, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
Kitamura
Kenichiro
K
Shinohara
Ayumi
A
Adachi
Masataka
M
Suenga
Ayaka
A
Maruyama
Toru
T
Miyanaka
Kei
K
Miyoshi
Taku
T
Shiraishi
Naoki
N
Nonoguchi
Hiroshi
H
Otagiri
Masaki
M
Tomita
Kimio
K
Suenaga
Ayaka
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000188:drug therapy* / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005290:Ferric Compounds / Q000008:administration & dosage*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D007501:Iron / Q000494:pharmacology; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000378:metabolism / Q000628:therapy; D008297:Male; D008875:Middle Aged; D016877:Oxidants / Q000494:pharmacology; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D006435:Renal Dialysis; D012709:Serum Albumin / Q000032:analysis / Q000378:metabolism*
D001798:Blood Proteins; D005290:Ferric Compounds; D016877:Oxidants; D012709:Serum Albumin; C000499:ferric oxide; D006861:Hydrogen Peroxide; D007501:Iron