Effect of deferoxamine on retinal lipid peroxidation in experimental uveitis.
OBJECTIVE
To examine the effect of deferoxamine, an effective iron chelator, on experimental autoimmune uveitis. Because deferoxamine has been shown to reduce iron-catalyzed hydroxyl radical generation, the in vivo effect was sought in the experimental autoimmune uveitis-mediated retinal lipid peroxidation, which is presumably induced by the inflammatory cell-derived oxygen radicals including hydroxyl radicals.


METHODS
The experimental uveitis was induced in Lewis rats by retinal S-antigen. Deferoxamine infusion by osmotic pumps was started 2 days before the onset of the disease and was continued for 7 days. The extent of retinal lipid peroxidation was measured by the production of conjugated dienes, ketodienes, and thiobarbituric acid active substances. The inflammation associated free radical activity was measured by the luminol-amplified chemiluminescence.


RESULTS
Levels of conjugated dienes, ketodienes, and thiobarbituric acid reactive substances were significantly decreased in the deferoxamine-treated animals. With Student's t test, the P values are < 0.025 for conjugated dienes between deferoxamine- and sham-treated animals; < 0.025 for ketodienes between deferoxamine- and sham-treated animals; and < 0.01 for thiobarbituric acid reactive substances between deferoxamine- and sham-treated animals. With in vitro addition of 10 mM deferoxamine, the free radical generation of inflamed retina was suppressed by nearly 40%.


CONCLUSIONS
The administration of deferoxamine resulted in reduction of retinal lipid peroxidation. Because photoreceptors contain a high proportion of polyunsaturated fatty acids, deferoxamine, in turn, will act to ameliorate the experimental autoimmune uveitis-mediated retinal degeneration.
Wu
G S
GS
Doheny Eye Institute, University of Southern California, School of Medicine, Los Angeles 90033.
Walker
J
J
Rao
N A
NA
D000818:Animals; D002829:Choroid / Q000378:metabolism / Q000473:pathology; D003676:Deferoxamine / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005609:Free Radicals / Q000378:metabolism; D015918:Infusion Pumps, Implantable; D015227:Lipid Peroxidation / Q000187:drug effects*; D051381:Rats; D011917:Rats, Inbred Lew; D012160:Retina / Q000378:metabolism* / Q000473:pathology; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014605:Uveitis / Q000188:drug therapy* / Q000473:pathology
D005609:Free Radicals; D017392:Thiobarbituric Acid Reactive Substances; D003676:Deferoxamine