Induction of protein oxidation by intravenous iron in hemodialysis patients: role of inflammation.
BACKGROUND
Oxidative stress and inflammation contribute to the high prevalence and severity of atherosclerosis, infections, and beta2-microglobulin amyloidosis; and thus, to reduced survival rate and quality of life in hemodialysis (HD) patients. Inflammation induces oxidative stress by production of the oxidants: superoxide anion, hydrogen peroxide, and hypochlorite. Intravenous iron (IVIR), administered in HD patients to correct anemia, can release free iron, that may react with hydrogen peroxide to produce the strong oxidant hydroxyl radical. Inflammation-induced lipid and protein oxidation and IVIR-induced lipid oxidation were shown in HD patients. However, IVIR-induced protein oxidation and a relationship between inflammation and IVIR-induced oxidative stress have not been reported to date.


METHODS
We examined the effect of IVIR administration on markers of protein oxidation in HD patients (advanced oxidation protein products [AOPPs], thiol, and dityrosine) in relation to such inflammatory markers as C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-alpha). Iron saccharate, 100 mg, was administered to 19 HD patients for 1 hour after 3.5 hours of high-flux dialysis. Blood samples were drawn pre-HD, pre-IVIR, and post-IVIR for iron, transferrin, TNF-alpha, AOPP, thiol, total antioxidant capacity (TEAC), and dityrosine levels and pre-HD for ferritin and CRP levels.


RESULTS
IVIR administration induced a 37% increase in AOPP level (P < 0.001), which correlated positively with pre-HD CRP level (r = 0.72; P < 0.05) and was greater in patients with a greater pre-HD TNF-alpha level (P < 0.05). IVIR administration did not affect TEAC, thiol, dityrosine, or TNF-alpha levels.


CONCLUSIONS
IVIR administration induced an increase in protein oxidation (AOPP levels) that was related to the degree of inflammation.
Tovbin
David
D
Department of Nephrology, Soroka University Medical Center, Beer Sheva, Israel. dtovbin@bgumail.bgu.ac.il
Mazor
Dalia
D
Vorobiov
Marina
M
Chaimovitz
Cidio
C
Meyerstein
Naomi
N
D000368:Aged; D000369:Aged, 80 and over; D001798:Blood Proteins / Q000378:metabolism*; D005260:Female; D005290:Ferric Compounds / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D000077605:Ferric Oxide, Saccharated; D005937:Glucaric Acid; D017127:Glycation End Products, Advanced / Q000097:blood; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000503:physiopathology; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology; D006435:Renal Dialysis / Q000379:methods*; D012965:Sodium Chloride / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism; D013395:Sucrose / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*
D001798:Blood Proteins; D005290:Ferric Compounds; D017127:Glycation End Products, Advanced; D012965:Sodium Chloride; D013395:Sucrose; D000077605:Ferric Oxide, Saccharated; D005937:Glucaric Acid