Ferrous ion formation by ferrioxamine prepared from aged desferrioxamine: A potential prooxidant property

Gutteridge, John M.C.; Quinlan, Gregory J.; Swain, Jason; Cox, James A.

doi:10.1016/0891-5849(94)90188-0

Cited by 19 publications

(3 citation statements)

References 26 publications

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“…First, it has been suggested that desferal can be used to inhibit only reactions that are dependent on Fe 3+ reduction (e.g., the Haber-Weiss cycle) but not in those which depend on Fe 2+ oxidation (Fenton reaction) [47]. Second, although it is generally accepted that Fe 3+ -desferal is resistant to reduction [48], it has also been demonstrated that a Fe 3+ -desferal complex has the potential to autoreduce its chelated iron to the ferrous state, and thereby generate ROS [49]. Third, it is possible that other radicals that are not detected by proxyl fluorescamine might contribute to the observed degradation (e.g., ferryl or perferryl radicals [22,43]).…”

Section: Discussionmentioning

confidence: 99%

Metal contaminants promote degradation of lipid/DNA complexes during lyophilization

Molina¹,

Anchordoquy²

2007

Biochimica et Biophysica Acta (BBA) - Biomembranes

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Oxidation reactions represent an important degradation pathway of nucleic acid-based pharmaceuticals. To evaluate the role of metal contamination and chelating agents in the formation of reactive oxygen species (ROS) during lyophilization, ROS generation and the stability of lipid/DNA complexes were investigated. Trehalose-containing formulations were lyophilized with different levels of transition metals. ROS generation was examined by adding proxyl fluorescamine to the formulations prior to freeze-drying. Results show that ROS were generated during lyophilization, and both supercoil content and transfection rates decreased as the levels of metal-induced ROS increased. The experiments incorporating chelators demonstrated that some of these agents (e.g., DTPA, desferal) clearly suppress ROS generation, while others (e.g., EDTA) enhance ROS. Surprisingly, there was not a strong correlation of ROS generated in the presence of chelators with the maintenance of supercoil content. In this study, we demonstrated the adverse effects of the presence of metals (especially Fe(2+)) in nonviral vector formulations. While some chelators attenuate ROS generation and preserve DNA integrity, the effects of these additives on vector stability during lyophilization are difficult to predict. Further study is needed to develop potent formulation strategies that inhibit ROS generation and DNA degradation during lyophilization and storage.

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Section: Discussionmentioning

confidence: 99%

Metal contaminants promote degradation of lipid/DNA complexes during lyophilization

Molina¹,

Anchordoquy²

2007

Biochimica et Biophysica Acta (BBA) - Biomembranes

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“…oryzae with abrogated FOB1 / FOB2 expression was marginally reduced at later time points ( Fig 7C , compare 4 h with earlier time points). These two phenomena can be explained by the fact that old or heat-damaged ferrioxamine (due to incubation at 37 o C) is unstable and undergoes an autoreduction step to release ferrous iron [ 52 ], that is taken up by the fungus. This assumption is corroborated by the yielding of a pink-colored complex in the presence of ferrozine in our experiment.…”

Section: Discussionmentioning

confidence: 99%

Fob1 and Fob2 Proteins Are Virulence Determinants of Rhizopus oryzae via Facilitating Iron Uptake from Ferrioxamine

et al. 2015

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Dialysis patients with chronic renal failure receiving deferoxamine for treating iron overload are uniquely predisposed for mucormycosis, which is most often caused by Rhizopus oryzae. Although the deferoxamine siderophore is not secreted by Mucorales, previous studies established that Rhizopus species utilize iron from ferrioxamine (iron-rich form of deferoxamine). Here we determined that the CBS domain proteins of Fob1 and Fob2 act as receptors on the cell surface of R. oryzae during iron uptake from ferrioxamine. Fob1 and Fob2 cell surface expression was induced in the presence of ferrioxamine and bound radiolabeled ferrioxamine. A R. oryzae strain with targeted reduced Fob1/Fob2 expression was impaired for iron uptake, germinating, and growing on medium with ferrioxamine as the sole source of iron. This strain also exhibited reduced virulence in a deferoxamine-treated, but not the diabetic ketoacidotic (DKA), mouse model of mucormycosis. The mechanism by which R. oryzae obtains iron from ferrioxamine involves the reductase/permease uptake system since the growth on ferrioxamine supplemented medium is associated with elevated reductase activity and the use of the ferrous chelator bathophenanthroline disulfonate abrogates iron uptake and growth on medium supplemented with ferrioxamine as a sole source of iron. Finally, R. oryzae mutants with reduced copies of the high affinity iron permease (FTR1) or with decreased FTR1 expression had an impaired iron uptake from ferrioxamine in vitro and reduced virulence in the deferoxamine-treated mouse model of mucormycosis. These two receptors appear to be conserved in Mucorales, and can be the subject of future novel therapy to maintain the use of deferoxamine for treating iron-overload.

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“…This could therefore limit the beneficial effect of administration of thiol antioxidants. A pro-oxidant activity for desferrioxamine has also recently been described [120].…”

Section: Antioxidant Therapymentioning

confidence: 98%

Free radicals and antioxidants in human diseases

Pincemaïl

1995

Analysis of Free Radicals in Biological Systems

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Increased free radicals formation derived from abnormal metabolism of oxygen has been implicated in over 100 different human diseases which may be classified into six categories: chemical and xenobiotic toxicity, radiation injury, hypen:~xygenation syndromes, inflammatory conditions, postischemic reperfusion injury and degenerative conditions. As their in vivo evidence always remains a difficult challenge, there is, however, a great deal of confusion about their precise role in the development of human diseases. Whatever the precise mechanism, preventing free radical generation by appropriate antioxidant therapy should provide beneficial clinical consequences.

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Ferrous ion formation by ferrioxamine prepared from aged desferrioxamine: A potential prooxidant property

Cited by 19 publications

References 26 publications

Metal contaminants promote degradation of lipid/DNA complexes during lyophilization

Metal contaminants promote degradation of lipid/DNA complexes during lyophilization

Fob1 and Fob2 Proteins Are Virulence Determinants of Rhizopus oryzae via Facilitating Iron Uptake from Ferrioxamine

Free radicals and antioxidants in human diseases

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