Inhibition of vincristine-induced retinal impairments by a specific PAF antagonist.
The alkaloid vincristine is widely used for its anti-leukemic and anti-tumor activity. However, the drug also displays considerable toxicity, particularly for the retina. Indeed, vincristine has been shown to induce alteration of photoreceptor outer segments in animals and impairment of scotopic vision in man. This type of retinopathy is an inflammatory disease in which PAF may be implicated and for which specific PAF antagonist may have a therapeutic role. Thus, we measured the effects of a new hetrapezine derived PAF antagonist, BN 50730, on a vincristine-induced retinopathy in the rat. Retinal impairments were established by recording several parameters of the electroretinogram (ERG) obtained from isolated retina. Our results indicate that, first, the increase in PIII duration induced by vincristine is significantly reduced by BN 50730 administration and, second, the decrease in the value of the PIII/b wave ratio caused by vincristine is partially inhibited by treatment with BN 50730. These experiments suggest that PAF is implicated in vincristine retinopathy and demonstrate the therapeutic effect of a specific antagonist of the mediator.
Doly
M
M
Laboratoire de Biophysique, Unité INSERM U71, Facultés de Médecine et de Pharmacie, Clermont-Ferrand, France.
Millerin
M
M
Bonhomme
B
B
Droy-Lefaix
M T
MT
Braquet
P
P
D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D004596:Electroretinography / Q000187:drug effects; D009924:Organ Culture Techniques; D010477:Perfusion; D010775:Photic Stimulation; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012164:Retinal Diseases / Q000139:chemically induced / Q000517:prevention & control*; D013777:Tetrazoles / Q000494:pharmacology*; D058924:Thienopyridines; D014230:Triazoles; D014750:Vincristine / Q000037:antagonists & inhibitors*
D001381:Azepines; D010972:Platelet Activating Factor; D013777:Tetrazoles; D058924:Thienopyridines; D014230:Triazoles; C066686:BN 50730; D014750:Vincristine