Ibuprofen, a putative anti-cataract drug, protects the lens against cyanate and galactose.
Cataract, the major cause of blindness world-wide, may be caused partly by modification of lens proteins by carbamylation and non-enzymic glycosylation (glycation) in some patients. Aspirin has been found to protect against these modifications and to prevent cyanate-induced opacification occurring in whole rate lenses. Ibuprofen is an aspirin-like anti-inflammatory drug which appeared as a protective factor against cataract in an Oxford case-control study. The binding of cyanate, galactose and glucose 6-phosphate to lens proteins, and the effect of ibuprofen on this reaction was investigated, as was cyanate-induced opacification in whole rat lenses. Labelled metabolite was incubated with bovine lens homogenate in the presence and absence of ibuprofen, and the incorporation of label into the lens homogenate was followed. Simultaneous and preincubation experiments were performed. Intact rat lenses were incubated in culture medium with and without cyanate and ibuprofen. The phase separation temperature was noted as the temperature at which opacity first appeared on cooling. Cyanate, galactose and glucose 6-phosphate bind progressively to lens proteins. Simultaneous incubation with ibuprofen reduces cyanate and galactose binding but not glucose 6-phosphate. Ibuprofen protects against opacities due to cyanate-induced phase separation. Ibuprofen has protected against cataract in the models of cataractogenesis in this study. It appears to have a different mechanism of action from that of aspirin. These studies provide some support for the idea, based on epidemiological findings, that ibuprofen might be a useful anti-cataract drug.
Roberts
K A
KA
Nuffield Laboratory of Ophthalmology, University of Oxford, U.K.
Harding
J J
JJ
D000818:Animals; D002386:Cataract / Q000517:prevention & control*; D002417:Cattle; D003459:Crystallins / Q000378:metabolism; D003485:Cyanates / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005690:Galactose / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007052:Ibuprofen / Q000627:therapeutic use*; D007908:Lens, Crystalline / Q000187:drug effects*; D008297:Male; D051381:Rats; D013696:Temperature
D003459:Crystallins; D003485:Cyanates; C024835:potassium cyanate; D007052:Ibuprofen; D005690:Galactose