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Iron-binding drugs targeted to lysosomes: A potential strategy to treat inflammatory lung disorders
Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Pathology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Respiratory Medicine UHL.
2005 (English)In: Expert Opinion on Investigational Drugs, ISSN 1354-3784, Vol. 14, no 8, 997-1008 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2005. Vol. 14, no 8, 997-1008 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-31880DOI: 10.1517/13543784.14.8.997Local ID: 17710OAI: diva2:252703
Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2011-01-12

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Persson, Lennart
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