Effects of different doses of
aspirin, compared to equimolar doses of
nitric oxide (NO)-donating
aspirin (
NCX 4016), and of a single dose of
paracetamol, compared to an equimolar dose of NO-donating
paracetamol (
NCX 701) were investigated in acute
zymosan-induced air pouch
inflammation in rats. Treatments were administered by orogastric route, and
interleukin-1beta (IL-1beta),
tumor necrosis factor-alpha (
TNF-alpha) and
prostaglandin E(2) (
PGE(2)) levels in the exudates were analysed 4 h after
zymosan injection by
enzyme immunoassay (EIA).
Aspirin,
at 10, 30 and 100 mg/kg doses, increased IL-1beta levels in exudates, however, only the highest dose lead to a significant increase when compared to control, whereas a significant increase in
TNF-alpha level was observed at all doses tested.
NCX 4016, at equimolar doses for
aspirin, i.e., 18.6, 55.8 and 186 mg/kg, respectively, did not cause any changes in exudate IL-1beta or
TNF-alpha levels. These effects were significantly different, when
aspirin was compared with the corresponding
NCX 4016 group. Nevertheless, the ability of
aspirin and
NCX 4016 to inhibit
PGE(2) synthesis in the exudate where comparable. Although
paracetamol significantly increased exudate
TNF-alpha level compared to the control group and
NCX 701 group, neither
paracetamol, nor
NCX701 treatments changed the levels of exudate IL-1beta significantly. As expected,
paracetamol and
NCX 701 showed poor
PGE(2) inhibition. At high doses,
aspirin and
NCX 4016 decreased the number of polymorphonuclear leukocytes in the exudate. However, this inhibition was not significantly different from the control group.
Paracetamol and NO-
paracetamol did not cause any change in the number of polymorphonuclear leukocytes in exudate. These results indicated that
aspirin and
NCX 4016 possessed different effects on
cytokine production or release, despite the fact that both drugs inhibited the synthesis of
PGE(2) in a similar way. Unlike
paracetamol, which increased exudate
TNF-alpha level,
NCX 701 had no effect on
TNF-alpha level in the exudates.