Fig. 3.

Dual inhibition of two branches of the AA acid cascade is synergistically effective in decreasing inflammatory mediators. (A) LPS administration led to significant increases in both PGE₂ (gray bar) and TXB₂ (black bar). t-AUCB is ineffective in significantly reducing PGE₂ by itself but when co-administered with a low dose of aspirin led to a synergistic reduction in PGE₂ (gray bar) levels. TXB₂ (black bar) levels were also reduced by t-AUCB, aspirin, and co-administration of t-AUCB with a lower dose of aspirin. Aspirin decreased the production of TXB₂ and PGE₂ in a dose-related manner. (B) LPS administration led to significant increases in both 5-HETE (black bar) and 15-HETE (gray bar). t-AUCB, effective by itself, however, when co-administered with MK 886, led to a synergistic decrease in the production of both HETEs. MK 886 decreased the production of 5-HETE 15-HETE in a dose-related manner. These data indicate that co-administration of a low dose of t-AUCB with a therapeutic dose of MK 886 can further reduce the levels of proinflammatory molecules 5-HETE and 15-HETE. The data are depicted as percentage of control mice receiving vehicle without LPS. Control values are TXB₂, 4.4 ± 1.4, and PGE₂, 0.5 ± 0.1 nM, 5-HETE, 3.4 ± 0.3 nM; 15-HETE, 6.6 ± 1.2 nM. * Significantly different (P > 0.05) determined by ANOVA followed by Tukey’s or Games-Howell’s posthoc comparison test.