[Simultaneous and sequential inhibition of the arachidonic acid cascade by inhibitors of phospholipase A2, cyclooxygenase and lipoxygenases in carrageenan edema and adjuvant arthritis in the rat].

According to the aim of the simultaneous and sequential inhibition of key enzymes of the arachidonic acid cascade, combinations of inhibitors of the phospholipase A2 (PLA2), cyclooxygenase (COX) and of lipoxygenases (LOX) were administered to rats with carrageenin edema and adjuvant arthritis, respectively. While the COX inhibitors diclofenac-Na and acetylsalicylic acid in combination with PLA2 and LOX inhibitors mostly gave overadditive antiinflammatory effects in the carrageenin edema, phenylbutazone in combination at most displayed additivity. Admixture of ascorbic acid led to subadditive effects. In the adjuvant arthritic rat, the combined administration of diclofenac-Na and dexamethasone yielded additive effects, only. The same result is valid for the combination of piroxicam and a LOX inhibitor in this model. Results are discussed with respect to the mode of action of substances as well as to the model peculiarities.