Iron-binding drugs targeted to lysosomes: A potential strategy to treat inflammatory lung disorders
2005 (English)In: Expert Opinion on Investigational Drugs, ISSN 1354-3784, Vol. 14, no 8, 997-1008 p.Article in journal (Refereed) Published
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.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-31880DOI: 10.1517/135437126.96.36.1997Local ID: 17710OAI: oai:DiVA.org:liu-31880DiVA: diva2:252703