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  • Title: Effect of WEB 2086-BS, an antagonist of platelet-activating factor receptors, on retinal vascularity in diabetic rats.
    Author: de la Cruz JP, Moreno A, Ruiz-Ruiz MI, García-Campos J, Sánchez de la Cuesta F.
    Journal: Eur J Pharmacol; 1998 Oct 30; 360(1):37-42. PubMed ID: 9845270.
    Abstract:
    Specific antagonists of platelet-activating factor (PAF) receptors inhibit platelet aggregation and thromboxane synthesis. These two processes have been implicated in the course of diabetic retinopathy. We assessed the effect of a specific PAF receptor antagonist, WEB 2086-BS (3-(4-(2-chlorophenyl)-9-methyl-6H-thieno(3,2-f) (1,2,4 triazolo-(4,3-a(1,4)-diazepine-2-yl)-1-(4-morpholinyl)-1-propanone) on retinal vascularity in a model of experimental streptozocin-induced diabetes in rats. Rats were divided into five experimental groups (10 animals/group): group I, non-diabetic group II, untreated diabetic group III, diabetic given 1 mg/kg per day of WEB 2086-BS (p.o.) group IV, diabetic given 5 mg/kg per day (p.o.) and group V, diabetic given 10 mg/kg per day (p.o.). After 3-month treatment, platelet aggregometry, platelet synthesis of thromboxane B2, aortic production of 6-keto-prostaglandin F1alpha, platelet and vascular lipid peroxidation, and percentage of the retinal area occupied by horseradish peroxidase-labeled vessels were measured. Untreated diabetic rats showed an increase in platelet reactivity, reduced 6-keto-prostaglandin F1alpha production, increased thromboxane B2 and lipid peroxides, and a decrease in the percentage of retinal area occupied by horseradish peroxidase-labeled vessels. WEB 2086-BS produced a decrease in platelet aggregation induced by collagen in whole blood, in thromboxane B2 synthesis and lipid peroxide production, and an increase in the percentage of retinal area occupied by horseradish peroxidase-labeled vessels (13.9+/-1.1% in group II and 9.9+/-0.8% in group V). There was a statistically significant linear correlation (Y= -0.72 + 137X, r2 = 0.7247, P < 0.0007) between thromboxane B2 values and the percentages of retinal area occupied by horseradish peroxidase-labeled vessels in the groups of animals treated with WEB 2086-BS.
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