Effects of valeryl salicylate, a COX-1 inhibitor, on models of acute inflammation in mice.
The effect of valeryl salicylate (VS), an inhibitor of cyclooxygenase-1 (COX-1), was evaluated in arachidonic acid or croton oil-induced ear oedema and carrageenan-induced paw oedema in mice. Ear oedema was induced by topical administration of arachidonic acid (2mg per ear; 20 microliters) or croton oil (1mg per ear; 20 microliters) to the inner surface of the left ear and the change in the ear's thickness was measured with a precision micrometer (Fisher, USA). VS significantly inhibited the arachidonic acid ear oedema after lh at doses of 1.5-45 micrograms per ear; however, only at the dose of 45 micrograms per ear was it able to significantly reduce the croton oil-induced oedema at 6h. Paw oedema was induced by the injection of 25 microliters of 1% carrageenan into the plantar aponeurosis of the right hind paw. The oedema was evaluated at 0.5, 1, 2, 4, 24, 48 and 72h. Previously in our experiments, we observed two peaks in paw oedema formation: one at 2h, in the early phase (0-4h), and the other, occurring at 48h after carrageenan injection, in the late phase (24-72h). The pre-treatment with VS significantly reduced the paw oedema at 2h, the same effect observed with celecoxib and indomethacin treatments. At 24h, VS did not inhibit oedema but significantly increased it mainly at 48h after carrageenan injection. These results showed that VS was pharmacologically active in these models and suggest that COX-1 may participate in the early and late phases of inflammation in the models studied.
Siqueira-Junior
Jarbas M
JM
Department of Pharmacology, Centre of Biological Sciences, Universidade Federal de Santa Catarina, Rua Ferreira Lima, 82, CEP: 88015-420, Florianópolis, -SC, Brazil. jarbasms@farmaco.ufsc.br
Peters
Rodrigo R
RR
Brum-Fernandes
Artur J de
AJ
Ribeiro-do-Valle
Rosa M
RM
D000208:Acute Disease; D000818:Animals; D016718:Arachidonic Acid; D002351:Carrageenan; D000068579:Celecoxib; D003436:Croton Oil; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004431:Ear, External / Q000473:pathology; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D005528:Foot / Q000473:pathology; D007213:Indomethacin / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology*; D007509:Irritants; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011720:Pyrazoles; D012459:Salicylates / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007509:Irritants; D007527:Isoenzymes; D008565:Membrane Proteins; D011720:Pyrazoles; D012459:Salicylates; D013449:Sulfonamides; C401835:valerylsalicylate; D016718:Arachidonic Acid; D003436:Croton Oil; D002351:Carrageenan; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse; D000068579:Celecoxib; D007213:Indomethacin