The effects of iron dextran on the oxidative stress in cardiovascular tissues of rats with chronic renal failure

Abstract

Redox-active iron can promote oxidative stress and tissue injury by catalyzing hydroxyl radical generation and lipid peroxidation. Intravenous iron preparations are routinely administered in conjunction with erythropoietin to treat anemia in patients with chronic renal failure (CRF), a condition that is marked by oxidative stress and inflammation. This treatment frequently elevates iron burden, which can potentially intensify oxidative stress and, thus, cardiovascular disease in this population. We studied renal function and oxidative stress parameters in the cardiovascular tissues of CRF (5/6 nephrectomized) and sham-operated control rats 3 months after a single intravenous infusion of iron dextran (500 mg/kg). Arterial pressure was equally elevated and creatinine clearance was equally reduced in both iron-treated and -untreated CRF groups. Iron administration significantly raised the blood hemoglobin, serum iron concentration, and transferrin saturation in both CRF and control groups. Iron administration resulted in a significant rise in plasma concentration of lipid peroxidation product, malondialdehyde in the CRF rats, and an insignificant rise in the control group. Plasma oxidized low-density lipoprotein (LDL) concentration was increased in the CRF groups, and was not affected by iron administrations. Iron administration raised nitrotyrosine abundance in the aorta of CRF but not in the control group. Left ventricular tissue abundance of p22(phox) subunit of NAD(P)H oxidase was elevated in CRF group and was not affected, whereas p67(phox) subunit abundance was raised by prior iron administration. Iron administration insignificantly lowered aorta p22(phox), but had no effect on p67(phox) subunit abundance in the treated CRF group. Previous iron administration significantly lowered superoxide dismutase and catalase abundance in the aorta and glutathione peroxidase in the left ventricle of CRF animals, but did not significantly change these parameters in the iron-treated control animals. A single intravenous injection of iron dextran increased oxidative stress in the cardiovascular tissues in the CRF group, but not the control rats, pointing to heightened susceptibility to iron-mediated toxicity in CRF. However, administration of iron dextran did not adversely affect kidney function, and favorably affected hemoglobin concentration in rats with CRF induced by renal mass reduction. Further studies are needed to explore the effects of other parenteral iron preparations, repeated intravenous iron administration, and presence of comorbid conditions such as diabetes.