The effect of
fosfosal, a non-acetylated
salicylic acid derivative, on the content of
prostaglandin E2 (
PGE2) and the migration of polymorphonuclear leukocytes in inflammatory exudates induced by s.c. implantation of 0.5%
carrageenan soaked sponges in rats has been determined.
Fosfosal, which does not inhibit PG synthesis in vitro, is capable of reducing, in a dose-dependent manner, the
PGE2 content of the exudates, with a maximum reduction of 50-60% at a total dose of 100 mg/kg i.p.
Acetylsalicylic acid was slightly more potent (68% reduction, 2
x 50 mg/kg i.p.). Six hours after
fosfosal administration,
salicylic acid, the principal metabolite of
fosfosal, accumulated in the exudates at concentrations of about 100 micrograms/ml. These concentrations were sufficient to inhibit PG
synthetase activity in vitro. Neither
fosfosal nor acetylsalicyclic
acid affected polymorphonuclear leukocyte migration at doses which significantly reduced the concentrations of
PGE2.
Indomethacin, used as reference, reduced leukocyte migration by 28 and 45% at a dose of 1 and 10 mg/kg i.p. respectively. The results indicate that
fosfosal, in spite of its lack of effect on PG biosynthesis in vitro, exerts an effect on the inflammatory locus in vivo which may account, at least in part, for its anti-inflammatory activity. Moreover, our results confirm that the inhibition of PG synthesis and leukocyte migration are mediated by different mechanisms.