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Action of deferoxamine against Pneumocystis carinii.
- Source :
-
Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2001 Dec; Vol. 45 (12), pp. 3560-5. - Publication Year :
- 2001
-
Abstract
- We found earlier that deferoxamine (DFO), a drug used for treatment of iron overload, is active against a rat model of Pneumocystis carinii pneumonia (PCP). We had assumed a mode of action by deprivation of nutritional iron; however, data here show that DFO penetrates P. carinii, causing irreversible damage, thus indicating a different mode of action. Penetration was demonstrated by showing DFO uptake by high-pressure liquid chromatography analysis. By using calcein-AM as an indicator, exposure to DFO was shown to cause a reduction in P. carinii cytoplasmic free iron. Exposure to >or=100 microM DFO for >or=8 h in vitro caused growth to cease and cell numbers to decline over several days. This direct and irreversible damage to P. carinii led to the prediction that infrequent delivery of DFO to the lungs via an aerosol would be an effective treatment in the animal model of PCP. This prediction was confirmed by demonstrating that a once-a-week aerosol treatment of rats was 100% effective both as a prophylactic and as a curative treatment in a rat model of PCP.
- Subjects :
- Aerosols
Animals
Chelating Agents pharmacokinetics
Chelating Agents therapeutic use
Cytoplasm metabolism
Deferoxamine pharmacokinetics
Deferoxamine therapeutic use
Half-Life
Humans
Injections, Intraperitoneal
Iron metabolism
Pneumocystis metabolism
Pneumonia, Pneumocystis drug therapy
Pneumonia, Pneumocystis microbiology
Rats
Rats, Sprague-Dawley
Chelating Agents pharmacology
Deferoxamine pharmacology
Pneumocystis drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 0066-4804
- Volume :
- 45
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Antimicrobial agents and chemotherapy
- Publication Type :
- Academic Journal
- Accession number :
- 11709340
- Full Text :
- https://doi.org/10.1128/AAC.45.12.3560-3565.2001