Ocular toxicity of desferrioxamine--an example of copper promoted auto-oxidative damage?
Three patients with rheumatoid disease were given the 'iron chelating' drug desferrioxamine (DFX), which also has an appreciable affinity for copper. The drug was injected cautiously, in lower doses than in patients with thalassaemia, and intramuscularly to evaluate its anti-inflammatory effects. Two of the three patients developed ocular abnormalities. One patient, who also received methyldopa, developed severe but reversible visual failure associated with an abnormal electro-oculogram (EOG); another showed reversible depression of the EOG. Analysis of the cerebrospinal fluid (CSF) of this patient showed an increase in phenanthroline detectable (non-caeruloplasmin-bound) copper. Analysis of the CSF of the third patient, who did not develop any clinical or electrophysiological ocular abnormalities, was normal. Haematological assessments indicated that all three patients probably had reduced iron stores. With in-vitro systems DFX was shown to mobilise copper from albumin and to facilitate copper movement across a cell membrane model, a property that was enhanced by methyldopa. Our observations are consistent with the concept that in rheumatoid patients low iron stores may result in binding of copper by DFX and that this may be of central importance in causing the ocular toxicity of DFX.
Department of Neurology, Medical School, University of Birmingham.
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H
Pall
D R
DR
Blake
P
P
Winyard
J
J
Lunec
A
A
Williams
P A
PA
Good
E E
EE
Kritzinger
A
A
Cornish
R C
RC
Hider
D000368:Aged; D003300:Copper / Q000134:cerebrospinal fluid; D003676:Deferoxamine / Q000009:adverse effects*; D004585:Electrooculography; D004596:Electroretinography; D005074:Evoked Potentials, Visual; D005128:Eye Diseases / Q000139:chemically induced*; D005260:Female; D006801:Humans; D008297:Male; D008750:Methyldopa / Q000627:therapeutic use; D008875:Middle Aged; D012216:Rheumatic Diseases / Q000188:drug therapy; D012709:Serum Albumin / Q000378:metabolism; D014786:Vision Disorders / Q000139:chemically induced
D012709:Serum Albumin; D008750:Methyldopa; D003300:Copper; D003676:Deferoxamine