Doly M, Millerin M, Bonhomme B, Droy-Lefaix M T, Braquet P
Laboratoire de Biophysique, Unité INSERM U71, Facultés de Médecine et de Pharmacie, Clermont-Ferrand, France.
Lens Eye Toxic Res. 1992;9(3-4):529-35.
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.
生物碱长春新碱因其抗白血病和抗肿瘤活性而被广泛使用。然而，该药物也表现出相当大的毒性，尤其是对视网膜。事实上，已表明长春新碱会导致动物光感受器外段改变以及人类暗视觉受损。这种类型的视网膜病变是一种炎症性疾病，其中血小板活化因子（PAF）可能与之相关，并且特定的PAF拮抗剂可能具有治疗作用。因此，我们测量了一种新的由六氢异喹啉衍生的PAF拮抗剂BN 50730对大鼠长春新碱诱导的视网膜病变的影响。通过记录从离体视网膜获得的视网膜电图（ERG）的几个参数来确定视网膜损伤。我们的结果表明，首先，BN 50730给药可显著降低长春新碱诱导的PIII持续时间增加，其次，BN 50730治疗可部分抑制长春新碱引起的PIII/b波比值降低。这些实验表明PAF与长春新碱视网膜病变有关，并证明了该介质特异性拮抗剂的治疗作用。
