GENTAMICIN-INDUCED MOBILIZATION OF IRON FROM RENAL CORTICAL MITOCHONDRIA

Iron, presumably by participating in generation of hydroxyl radical or other oxidant species or initiation of lipid peroxidation, has been s hown to play an important role in several models of tissue injury, inc luding acute renal failure induced by the antibiotic gentamicin. Howev er, the sources of iron remain unknown. Rat renal mitochondria incubat ed at 37-degrees-C with gentamicin resulted in a time- (15-60 min) and a dose-dependent (0.01-5 mM) iron release as measured by formation of iron-bathophenanthroline sulfonate complex FeII-(BPS)3 [at 60 min, co ntrol: 1.2 +/- 0.1 nmol/mg protein, n = 7; gentamicin (5 mM): 5.1 +/- 0.4 nmol/mg protein, n = 7]. No formation of FeII(BPS)3 complex was de tected in the absence of mitochondria or when incubations were carried out at 0-degrees-C. Similar results were obtained when 2,2'-dipyridyl , another iron chelator, was used for measurement of iron release. On the basis on our previous study that gentamicin enhances generation of hydrogen peroxide by renal cortical mitochondria, we examined whether effect of gentamicin on iron release is mediated by hydrogen peroxide . Catalase (which decomposes hydrogen peroxide), but not heat-inactiva ted catalase, as well as pyruvate, a potent scavenger of hydrogen pero xide, prevented gentamicin-induced iron mobilization. Superoxide dismu tase, a scavenger of superoxide anion, or hydroxyl radical scavengers (dimethylthiourea or sodium benzoate) had no effect. Taken together, t he data with scavengers indicate that gentamicin-induced iron mobiliza tion from mitochondria is mediated by hydrogen peroxide. We confirmed the ability of hydrogen peroxide added directly to renal cortical mito chondria to release iron. Our results demonstrate that gentamicin indu ces release of iron from mitochondria and that this is mediated throug h generation of hydrogen peroxide. Our results also indicate that mito chondria should be considered as a potential source of iron for genera tion of other oxidant species or initiation of lipid peroxidation in o ther models of tissue injury.