歯周組織炎治療薬TCPS軟膏に関する研究

歯髄細胞でのアラキドン酸とその代謝産物の遊離に対する抗炎症薬プレステロンの効果

抄録

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.