Trapidil inhibits endothelial cell proliferation and angiogenesis in the chick chorioallantoic membrane and in the rat cornea.
The effects of trapidil, a coronaro-active drug which has been shown to inhibit the mitogenic activity of platelet derived growth factor (PDGF), have been investigated on the proliferation of the human endothelial cells (HUV-EC-C), on the neovascularization in the chorioallantoic membrane of the chick embryo (CAM) as well as on the angiogenesis of rat cornea following chemical injury. The proliferation of HUV-EC-C in the presence of trapidil (25 and 250 micrograms/mL) was significantly inhibited by 19 and 25% respectively, compared to controls. On 2-days old CAMs, agarose disks containing 100-150 micrograms of trapidil produced an avascular zone indicating significant antiangiogenic activity, while control agarose disks were without effect. Corneal neovascularization was induced by applying a silver nitrate/potassium nitrate applicator to the rat eyes. A 6-day-treatment with eye drops of a solution of 10 mg/mL trapidil significantly decreased the rate of vessel growth compared with vehicle controls. The antiangiogenic activity of trapidil was markedly increased by the association with hydrocortisone (1.34 mg/mL). These results suggest that trapidil, alone or in combination with a steroid, could be a promising candidate for the therapy of corneal diseases in which alterations induced by neovascular growth play a substantial role.
Benelli
U
U
Institute of Ophthalmology, University of Pisa, Italy.
Lepri
A
A
Nardi
M
M
Danesi
R
R
Del Tacca
M
M
D000482:Allantois / Q000098:blood supply* / Q000196:embryology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects; D002642:Chick Embryo; D002823:Chorion / Q000098:blood supply* / Q000196:embryology; D003315:Cornea / Q000187:drug effects; D016510:Corneal Neovascularization / Q000139:chemically induced / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009566:Nitrates; D009883:Ophthalmic Solutions; D017680:Potassium Compounds; D051381:Rats; D017208:Rats, Wistar; D012835:Silver Nitrate; D014192:Trapidil / Q000494:pharmacology* / Q000627:therapeutic use; D014471:Umbilical Veins; D014665:Vasodilator Agents / Q000494:pharmacology* / Q000627:therapeutic use
D000893:Anti-Inflammatory Agents; D009566:Nitrates; D009883:Ophthalmic Solutions; D017680:Potassium Compounds; D014665:Vasodilator Agents; D012835:Silver Nitrate; D014192:Trapidil; C023844:potassium nitrate; D006854:Hydrocortisone