Abstract
The effects of phenolic anti-inflammatory drug, MK-447, on prostaglandin (PG) I 2 and thromboxane (TX) A 2 biosynthesis by rat dental pulp tissue were evaluated in the presence of 10 mM mannitol (MA) or 1 mM ascorbic acid with 0.3 mM Fe 2+ (A + F). Although MK-447 alone at 1 and 10 μM had no significant effects, MK-447 at 100 μM stimulated both PGI 2 and TXA 2 biosynthesis, and suppressed the lipidperoxidation in the pulp tissue as estimated by thiobarbituric acid method. MA also reduced the lipid peroxidation, but had no effect on PG and TX production. However, in the presence of MA, the stimulatory effect of MK-447 was potentiated, and the significant effects were observed at concentrations higher than 1 μM. In contrast, A + F remarkarbly stimulated the lipid peroxidation, and inhibited both PG and TX biosynthesis. In the presence of A + F, MK-447 showed no stimulatory effect, and contrary, at 100 μM inhibited PG and TX production. These results suggest that the cellular levels of lipid peroxidation exert a significant influence on the effects of phenolic anti-inflammatory drugs like MK-447 on PG biosynthesis. The possible mechanism of action for such drugs has been discussed in view of the significance of lipid peroxidation in inflammatory condition.
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