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Inflammatory pulmonary diseases / iron-chelating therapy
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PostPosted: Sun Jul 31, 2005 4:50 pm    Post subject: Inflammatory pulmonary diseases / iron-chelating therapy Reply with quote

Iron-binding drugs targeted to lysosomes: a potential strategy to treat
inflammatory lung disorders.
Persson HL, Richardson DR
Expert Opin Investig Drugs. 2005 Aug ; 14(Cool: 997-1008

In many inflammatory lung disorders, an abnormal assimilation of
redox-active iron will exacerbate oxidative tissue damage. It may be
that the most important cellular pool of redox-active iron exists
within lysosomes, making these organelles vulnerable to oxidative
stress. In experiments employing respiratory epithelial cells and
macrophages, the chelation of intra-lysosomal iron efficiently
prevented lysosomal rupture and the ensuing cell death induced by
hydrogen peroxide, ionising radiation or silica particles. Furthermore,
cell-permeable iron-binding agents (weak bases) that accumulate within
lysosomes due to proton trapping were much more efficient for
cytoprotection than the chelator, desferrioxamine. On a molar basis,
the weak base alpha-lipoic acid plus was 5000 times more effective than
desferrioxamine at preventing lysosomal rupture and apoptotic cell
death in cell cultures exposed to hydrogen peroxide. Thus,
iron-chelating therapy that targets the lysosome might be a future
treatment strategy for inflammatory pulmonary diseases.

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