Antiinflammatory action of salicylates: aspirin is not a prodrug for salicylate against rat carrageenin pleurisy

Abstract

A current hypothesis postulates that the antiinflammatory effect of aspirin (acetylsalicylic acid) is mediated by its metabolite salicylic acid through inhibition of PGE 2 synthesis. We tested this hypothesis in rats with carrageenin-induced pleurisy. Aspirin or salicylate, given orally, reduced exudation and cell migration into the pleural cavity, aspirin being more potent than salicylate. The antiinflammatory effect of aspirin cannot be explained only in terms of salicylate formation. Doses of aspirin and salicylate that inhibit inflammation by 50% result in salicylate levels in the exudate of 70±12 and 323±17 μg/ml, respectively. At a significant antiinflammatory dose (100 mg/kg), salicylate did not reduce the prostaglandin and thromboxane content of the exudate. This indicates that inhibition of cyclooxygenase is not a likely mechanism for the antiinflammatory effect of salicylate. Salicylate only reduced the amount of 6-keto-PGF 1α in the exudate at higher doses (200 mg/kg), while aspirin at an equally antiinflammatory dose (50 mg/kg) reduced the content of 6-keto-PGF 1α, TXB 2, PGD 2 but not of PGE 2 in the exudate. It therefore seems unlikely that an inhibition of PGE 2 synthesis is the common mechanism by which aspirin and salicylate exert their antiinflammatory effects. These results do not supported the hypothesis that aspirin is a prodrug for salicylate but rather indicate that both compounds may exert their antiinflammatory effects partly by different mechanisms.