Effects of a basic anti-inflammatory agent, MK-447, on rat carrageenin-induced pleurisy

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It was reported that a basic anti-inflammatory agent, MK-447, accelerated the conversion of PGG2 to PGH2 through scavenging of an oxidant. On the other hand, we showed that an effect of MK-447 on PG endoperoxide biosynthesis was stimulatory or inhibitory, depending on the concentration of cofactors, hemoglobin and tryptophan. The present paper describes effects of the agent in vivo using carrageenin induced rat pleuristy. In this model, exudation of plasma protein into pleural cavity, measured by the amount of albumin-bound dye, reached the maximum at 5 hr after carrageenin. The contents of PGE2, PGF2α, 6-keto-PGF1α and TxB2 in the pleural fluid, quantitated by GC-MS, showed different time courses. The change of PGE2 level corresponded well to that of the dye exudation. In addition, use of selective inhibitors of PGI or Tx isomerase strengthened the supposition that PGE2 might be the most important PG for accumulation of the pleurl fluid. Aspirin (100 mg/kg) inhibited the exudation until 5 hr. MK-447 (0.3, 1.0 and 3.0 mg/kg) also inhibited it dose-dependently upto 5 hr, and reduced the PGE2 content in the pleural fluid at 3 hr as did aspirin. It may be conceivable that PG endoperoxide synthesis in the cells, which dominantly released PGE2 into the pleural cavity, was inhibited by MK-447. The anti-inflammatory action of the agent could be explained by the inhibition of PGE2 biosynthesis.
日本炎症・再生医学会の論文