Document Detail


Deferoxamine mesylate is toxic for retinal pigment epithelium cells in vitro, and its toxicity is mediated by p38.
MedLine Citation:
PMID:  20380623     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Deferoxamine mesylate is clinically used as a chelating agent but might induce retinopathy. To evaluate its effect on the retinal pigment epithelium (RPE), porcine RPE cells were stimulated with deferoxamine. Cell death was assessed with trypan blue exclusion assay. To investigate the pathway of cell death, the mitogen-activated protein kinases (MAPKs) Erk, JNK, and p38 were inhibited with U0126, SP600125, and SB203580, respectively. Their activity was determined by Western blot. Deferoxamine induces significant cell death in RPE cells, accompanied by phosphorylation of p38 and Erk. Inhibition of p38 attenuates cell death. In conclusion, deferoxamine is directly toxic on RPE cells, its toxicity depending on p38.
Authors:
Alexa Klettner; Stefan Koinzer; Vicki Waetzig; Thomas Herdegen; Johann Roider
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Cutaneous and ocular toxicology     Volume:  29     ISSN:  1556-9535     ISO Abbreviation:  Cutan Ocul Toxicol     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-05-05     Completed Date:  2010-07-21     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101266892     Medline TA:  Cutan Ocul Toxicol     Country:  England    
Other Details:
Languages:  eng     Pagination:  122-9     Citation Subset:  IM    
Affiliation:
University of Kiel, University Medical Center, Department of Ophthalmology, Germany. aklettner@auge.uni-kiel.de <aklettner@auge.uni-kiel.de>
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MeSH Terms
Descriptor/Qualifier:
Animals
Anthracenes / therapeutic use
Blotting, Western
Butadienes / therapeutic use
Cell Death / drug effects
Cells, Cultured
Deferoxamine / toxicity*
Dose-Response Relationship, Drug
Hydrogen Peroxide / toxicity
Imidazoles / therapeutic use
Iron Chelating Agents / toxicity*
Nitriles / therapeutic use
Protein Kinase Inhibitors / therapeutic use
Pyridines / therapeutic use
Retinal Pigment Epithelium / enzymology,  pathology*
Swine
Trypan Blue
p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors,  physiology*
Chemical
Reg. No./Substance:
0/Anthracenes; 0/Butadienes; 0/Imidazoles; 0/Iron Chelating Agents; 0/Nitriles; 0/Protein Kinase Inhibitors; 0/Pyridines; 0/SB 203580; 0/U 0126; 0/anthra(1,9-cd)pyrazol-6(2H)-one; 70-51-9/Deferoxamine; 72-57-1/Trypan Blue; 7722-84-1/Hydrogen Peroxide; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases

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