Role of iron in postischemic renal injury in the rat

Abstract

To determine whether iron participates in free radical-mediated postischemic renal injury and lipid peroxidation, we examined the effects of removal of endogenous iron or provision of exogenous iron following renal ischemia, as well as the effects of renal ischemia and reperfusion on renal venous and urinary "free" iron. Rats underwent 60 minutes of renal ischemia and were studied after either 24 hours (inulin clearance) or 15 minutes (renal malondialdehyde content) of reperfusion. Infusion of the iron chelator deferoxamine (200 mg/kg/hr) during the first 60 minutes of reperfusion resulted in a marked improvement in renal function (inulin clearance: 879 +/- 154 vs. 314 +/- 74 microliter/min; P less than 0.025) and a reduction in lipid peroxidation (renal malondialdehyde: 0.449 +/- 0.06 vs. 0.698 +/- 0.08 mmol/mg prot; P less than 0.05) compared to control animals. Infusion of 50 mg/kg/hr deferoxamine also protected renal function after ischemia (inulin clearance: 624 +/- 116 vs. 285 +/- 90 microliter/min; P less than 0.05) and resulted in less histologic injury. Iron-saturated deferoxamine had no protective effect. Conversely, infusion of the iron complex EDTA-FeCl3 during reperfusion exacerbated postischemic renal dysfunction and lipid peroxidation. Following renal ischemia there was no detectable increase in "free" iron in arterial or renal venous plasma. However, urinary "free" iron increased 10- to 20-fold following reperfusion. Iron chelators which underwent filtration and gained access to this free iron in the urine (free deferoxamine or inulin-conjugated deferoxamine) provided protection, whereas a chelator confined to the vascular space (dextran-conjugated deferoxamine) did not.(ABSTRACT TRUNCATED AT 250 WORDS)

Lipocalin 2 Antagonizes the Proangiogenic Action of Ras in Transformed Cells

“…To determine the effect of iron on lipocalin 2 -induced inhibition of angiogenesis, we used deferoxamine mesylate (2-5 Amol/L), an iron chelating agent. Deferoxamine mesylate, which depletes iron from the intracellular pool (27), partially reversed the inhibitory effect of lipocalin 2 on VEGF secretion (Fig. 7B).…”

Lipocalin 2 Diminishes Invasiveness and Metastasis of Ras-transformed Cells

“…Deferoxamine mesylate (2-5 M; DFO), an iron chelating agent that can deplete iron from the intracellular pool (29), changed the morphology of RL cells to a mesenchymal phenotype and suppressed E-cadherin expression (Fig. 7A), indicating that iron was necessary for E-cadherin expression.…”

L-Carnitine Ameliorates Glycerol-Induced Myoglobinuric Acute Renal Failure in Rats

“…[7] On the other hand, the porphyrin ring of myoglobin is rapidly catabolized in tubules, thereby releasing its iron content. [1,8,9] Any released free iron could participate in the Fenton and Haber-Weiss chemistry, where catalytic amounts of iron are sufficient to yield hydroxyl radicals (OHº) from O 2 − and hydrogen peroxide (H 2 O 2 ), collectively known as ROS. [8,9] Hydroxyl radical is capable of abstracting a hydrogen atom from polyunsaturated fatty acids to initiate lipid peroxidation.…”

“…[1,8,9] Any released free iron could participate in the Fenton and Haber-Weiss chemistry, where catalytic amounts of iron are sufficient to yield hydroxyl radicals (OHº) from O 2 − and hydrogen peroxide (H 2 O 2 ), collectively known as ROS. [8,9] Hydroxyl radical is capable of abstracting a hydrogen atom from polyunsaturated fatty acids to initiate lipid peroxidation. [8] The heme group in myoglobin itself, which can redox cycle between different oxidation states, promotes lipid peroxidation reactions.…”