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 α-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. © 2005 Ashley Publications Ltd.
CITATION STYLE
Persson, H. L., & Richardson, D. R. (2005, August). Iron-binding drugs targeted to lysosomes: A potential strategy to treat inflammatory lung disorders. Expert Opinion on Investigational Drugs. https://doi.org/10.1517/13543784.14.8.997
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