Effects of betamethasone, sulindac and quinacrine drugs on the inflammatory neoangiogenesis response induced by polyurethane sponge implanted in mouse.
In this study, we showed the effect of the betamethasone, sulindac and quinacrine alone or combined, on the inflammatory angiogenesis promoted by polyurethane sponge on mice. The main finding reported here is that the formation of new blood vessels was strongly inhibited by low concentration of betamethasone, sulindac or quinacrine, whether alone or in combination. It is known that steroidal anti-inflammatory drugs inhibit the enzymes required for the production of prostaglandins through a nuclear glucocorticoid receptor (GR) mediated mechanism. This mechanism may occur in endothelial cells as well. Considering that activity of cyclo-oxigenases 1 and 2 is inhibited by sulindac, and that these enzymes are located in the stromal tissue, we propose that the anti-angiogenic effect of these agents may occur via inhibition of both COX isoforms. On the other hand, quinacrine inhibited PLA2 activity, and we propose here that the anti-angiogenic effect occurs via inhibition of the enzyme PLA2. The potentiated effect of the association of betamethasone, sulindac and quinacrine may have some therapeutic benefit in the control of pathological angiogenesis. Further studies are required to validate these propositions.
Illanes
Julio
J
Programa de Morfología, Instituto de Ciencias Biomédicas (ICBM) Facultad de Medicina, Universidad de Chile, Santiago-Chile.
Dabancens
Alfredo
A
Acuña
Olga
O
Fuenzalida
Marcela
M
Guerrero
Anibal
A
Lopez
Claudia
C
Lemus
David
D
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001623:Betamethasone / Q000627:therapeutic use*; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D004359:Drug Therapy, Combination; D005260:Female; D007527:Isoenzymes / Q000187:drug effects; D008565:Membrane Proteins; D051379:Mice; D009389:Neovascularization, Pathologic / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D011140:Polyurethanes; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects; D011796:Quinacrine / Q000627:therapeutic use*; D013467:Sulindac / Q000627:therapeutic use*; D015503:Surgical Sponges
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007527:Isoenzymes; D008565:Membrane Proteins; D011140:Polyurethanes; D013467:Sulindac; D001623:Betamethasone; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse; D011796:Quinacrine