Abstract
The cyclooxygenase (COX) -2-selective nonsteroidal anti-inflammatory drugs (NSAIDs), coxibs are now known to increase cardiovascular risk. As such, rofecoxib has been removed from the U.S. market and sales of valdecoxib have been suspended. The past-generation NSAIDs and phospholipase A2 (PLA2) inhibitors are being refocused on as potential anti-inflammatory agents. Presteron, a base drug of the renewed TCPS (tetracycline Presteron) ointment, is an old NSAID having no adverse effects in particular to date. To analyze the anti-inflammatory function of presteron at the cellular level, clonal rat dental pulp cells RDP4-1 were labeled with [3H] -arachidonic acid for 24 h. The cells, pre-incubated with presteron or a counterpart for three minutes, were stimulated with bradykinin or a calcium ionophore: A23187. A23187, as well as bradykinin, induced release of arachidonic acid and its metabolites not from subconfluent cells but only from confluent cells at concentrations around 0.5μM. Presteron at 0.1-0.3μM suppressed the releases in a dose-dependent manner without affecting cell viability, while indomethacin did not. Dexamethasone completely inhibited them. In addition, 0.lμM presteron partly inhibited ovine COX-1 by 10.4%, but it did not inhibit human recombinant COX-2 at all. Thus, presteron inhibits the action of bradykinin, a potent inflammatory mediator, by suppressing Ca2+-tdependent cellular PLA2 (cPLA2) and/or secretory PLA2 (sPLA2), and COX-1, resulting in alleviation of inflammation.
