title: Effects of terutroban, a thromboxane/prostaglandin endoperoxide receptor antagonist, on retinal vascularity in diabetic rats.
abstract: BACKGROUND
  The aim of the present study is to investigate the effectiveness of terutroban, a selective antagonist of the thromboxane/prostaglandin endoperoxide receptor, in preventing retinal ischaemia in a model of diabetes in rats.
  
  
  METHODS
  Experimental diabetes was induced with streptozotocin. Rats were distributed into five groups (n = 20): (1) non-diabetic rats, (2) rats with diabetes (DR) treated with vehicle, (3) DR treated with aspirin (2 mg/kg/day p.o.), (4) DR treated with terutroban (5 mg/kg/day p.o.), (5) DR treated with terutroban (30 mg/kg/day p.o.). The follow-up period was 3 months. The main assessment was the percentage of retinal surface covered with vessels permeable to peroxidase. Platelet aggregation, aortic prostacyclin and nitric oxide production, plasma levels of lipid peroxides (thiobarbituric-acid-reactive substances) and 3-nitrotyrosine and serum levels of IL-6 were evaluated.
  
  
  RESULTS
  Diabetes induced a reduction in retinal vascularity (76.9%), aortic prostacyclin (37.8%) and nitric oxide production (35.0%), and increased platelet aggregation, lipid peroxides, 3-nitrotyrosine. When compared with vehicle-treated DR, terutroban increased the percentage of retinal surface covered by PVPP (38% for terutroban-5 and 61% for terutroban-30), aortic prostacyclin (188% for terutroban-5 and 146% for terutroban-30) and nitric oxide production (320% for terutroban-5 and 390% for terutroban-30). Moreover, terutroban reduced platelet reactivity (27.8–95.1%, according to the inducer), lipid peroxides (60.7% for terutroban-5 and 50.0% for terutroban-30), 3-nitrotyrosine (43.8% for terutroban-5 and 36.8% for terutroban-30) and IL-6 concentration (18.0% for terutroban-30). The effect of terutroban in retinal, nitrosative and aortic parameters was significantly higher than that of aspirin.
  
  
  CONCLUSIONS
  Terutroban significantly protected retinal vascularity from ischaemia in experimental diabetes, and this result could be attributed not only to its antiplatelet/antithrombotic activities but also to its vascular properties.
authors.affiliation: Laboratorio de Investigaciones Antitrombóticas e IsquemiaTisular (LIAIT), Department of Pharmacologyand Therapeutics, School of Medicine, University of Málaga, Málaga, Spain.
authors.forename: J P
authors.initials: JP
authors.lastname: De La Cruz
authors.forename: N
authors.initials: N
authors.lastname: Jebrouni
authors.forename: J A
authors.initials: JA
authors.lastname: López-Villodres
authors.forename: J
authors.initials: J
authors.lastname: Muñoz-Marín
authors.forename: A
authors.initials: A
authors.lastname: Guerrero
authors.forename: J A
authors.initials: JA
authors.lastname: González-Correa
mesh_terms: D000818:Animals; D001241:Aspirin / Q000627:therapeutic use; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D003930:Diabetic Retinopathy / Q000517:prevention & control*; D011464:Epoprostenol / Q000096:biosynthesis; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009281:Naphthalenes / Q000627:therapeutic use*; D010974:Platelet Aggregation / Q000187:drug effects; D011422:Propionates / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors; D012171:Retinal Vessels / Q000187:drug effects; D013311:Streptozocin
chemical_list: D009281:Naphthalenes; D011422:Propionates; D011982:Receptors, Prostaglandin; C055662:prostaglandin endoperoxide receptor; D013311:Streptozocin; C501362:terutroban; D011464:Epoprostenol; D001241:Aspirin