Deferoxamine mesylate is toxic for retinal pigment epithelium cells in vitro, and its toxicity is mediated by p38.
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.
Klettner
Alexa
A
University of Kiel, University Medical Center, Department of Ophthalmology, Germany. aklettner@auge.uni-kiel.de <aklettner@auge.uni-kiel.de>
Koinzer
Stefan
S
Waetzig
Vicki
V
Herdegen
Thomas
T
Roider
Johann
J
D000818:Animals; D000873:Anthracenes / Q000627:therapeutic use; D015153:Blotting, Western; D002070:Butadienes / Q000627:therapeutic use; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D003676:Deferoxamine / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006861:Hydrogen Peroxide / Q000633:toxicity; D007093:Imidazoles / Q000627:therapeutic use; D007502:Iron Chelating Agents / Q000633:toxicity*; D009570:Nitriles / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D055213:Retinal Pigment Epithelium / Q000201:enzymology / Q000473:pathology*; D013552:Swine; D014343:Trypan Blue; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*
D000873:Anthracenes; D002070:Butadienes; D007093:Imidazoles; D007502:Iron Chelating Agents; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D011725:Pyridines; C113580:U 0126; C432165:pyrazolanthrone; D006861:Hydrogen Peroxide; D048051:p38 Mitogen-Activated Protein Kinases; D014343:Trypan Blue; D003676:Deferoxamine; C093642:SB 203580