12-hydroxy-5-8-10-14-eicosatetraenoic-acid and Pulpitis

The effects of phenolic dental medicaments on lipoxygenase activities of rat dental pulp and human platelets were studied. The major product derived from [14C] arachidonic acid by the homogenate of rat dental pulp was 12-HETE (15-HETE). Eugenol and p-chlorophenol dose-dependently inhibited HETEs formation. The IC50 values of eugenol and p-chlorophenol were 0.62 and 0.34 mM respectively. The concentrations of these compounds that inhibit lipoxygenase were similar to those required to inhibit cyclooxygenase. These compounds also inhibited 12-lipoxygenase of human platelets with a similar range of concentrations. The results show that phenolic dental medicaments inhibit pulpal and platelet lipoxygenase. Thus, inhibition of arachidonic acid metabolism by phenolic dental medicaments via the lipoxygenase pathway may be involved in the analgesic and anti-inflammatory effects of the medicaments in endodontic therapy.

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Animals; Arachidonic Acids; Blood Platelets; Chlorophenols; Dental Pulp; Eugenol; Humans; Hydroxyeicosatetraenoic Acids; Lipoxygenase; Lipoxygenase Inhibitors; Male; Pulpitis; Rats; Rats, Inbred Strains

Pulp was experimentally inflamed by applying bacterial lipopolysaccharide (LPS). Changes in arachidonic acid (AA) metabolites were determined by measuring the conversion of exogenously added AA in pulp homogenates. The inflamed pulp produced 12-hydroxy-eicosatetraenoic acid (12-HETE), 6-keto-prostaglandin (PG) F1 alpha greater than PGE2, thromboxane B2 and 11-HETE, which was further identified with high-performance liquid chromatography. The LPS treatment caused a 2.0-fold increase in 12-HETE production at 1 h, a 3.8-fold increase in 6-keto-PGF1 alpha production at 12 h and increases in PGE2 and 11-HETE production of 8.8- and 5.5-fold, respectively, at 24 h. Vascular permeability in the inflamed pulp was measured by quantifying the amount of an extravasated dye; it increased markedly from 6 h and reached a peak at 12 h after the LPS application. When indomethacin (0.3-30 mg/kg, s.c.) was given before LPS, both the production of 6-keto-PGF1 alpha and PGE2 and the increase in vascular permeability were inhibited dose dependently. Exogenously applied PGE2 and PGI2 methyl ester reduced the inhibition of the increase in vascular permeability caused by indomethacin. Thus PGE2 and PGI2 may be involved in increases in vascular permeability in pulpal inflammation.

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; 6-Ketoprostaglandin F1 alpha; Animals; Arachidonic Acid; Arachidonic Acids; Capillary Permeability; Chromatography, High Pressure Liquid; Dental Pulp; Dinoprostone; Dose-Response Relationship, Drug; Hydroxyeicosatetraenoic Acids; Indomethacin; Lipopolysaccharides; Male; Pulpitis; Rats; Rats, Inbred Strains; Thromboxane B2