Iron and oxidative stress in renal insufficiency.
OBJECTIVE
Iron (Fe) can cause tissue injury and oxidative stress by catalyzing hydroxyl radical production and lipid peroxidation. Intravenous (i.v.) Fe preparations are routinely administered to treat anemia in patients with chronic renal failure (CRF), a condition marked by oxidative stress and inflammation. In an earlier study, we showed that iron overload augments oxidative stress in the cardiovascular tissues of CRF rats. This study was designed to expand these observations to other major organs.


METHODS
Rats were randomized into CRF (5/6 nephrectomized) and sham-operated control (CTL) groups. Each group was subdivided into Fe-loaded (single i.v. injection of iron dextran complex, 0.5 g/kg) and placebo-treated subgroups. After 13 weeks, systolic blood pressure, blood hemoglobin (Hb), plasma Fe concentration, lipid peroxidation products, superoxide generating enzyme, NAD(P)H oxidase, and antioxidant enzymes were determined.


RESULTS
Systolic blood pressure was equally elevated and creatinine clearance was equally reduced in both CRF groups. Fe administration raised Hb, serum Fe and transferrin saturation in both CRF and CTL groups. The plasma concentration of lipid peroxidation product, malondialdehyde, was increased by Fe injection in CRF rats but not the control group. Renal tissue abundance of gp91(phox) subunit of NAD(P)H oxidase was elevated in the untreated CRF group and was partially reduced in the iron dextran-treated CRF group. Tissue abundance of the antioxidant enzymes; superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) were decreased in both untreated and iron dextran-treated CRF groups.


CONCLUSIONS
CRF resulted in marked SOD, CAT and GPX deficiencies. A single i.v. administration of iron dextran in rats with CRF induced oxidative stress as measured by increased lipid peroxidation products and decreases in antioxidant enzymes.
Lim
Chun Soo
CS
Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Boramae Hospital, Seoul, Korea. sclimjy@snu.ac.kr
Vaziri
Nosratola D
ND
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D007275:Injections, Intravenous; D007501:Iron / Q000378:metabolism / Q000494:pharmacology*; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism; D009392:Nephrectomy; D018384:Oxidative Stress / Q000502:physiology*; D010750:Phosphoproteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism
D000975:Antioxidants; D010750:Phosphoproteins; C079789:neutrophil cytosol factor 67K; D007501:Iron; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D019255:NADPH Oxidases