Effect of aspirin, paracetamol and their nitric oxide donating derivatives on exudate cytokine and PGE2 production in zymosan-induced air pouch inflammation in rats

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-1β (IL-1β), tumor necrosis factor-α (TNF-α) and prostaglandin E2 (PGE2) 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-1β levels in exudates, however, only the highest dose lead to a significant increase when compared to control, whereas a significant increase in TNF-α 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-1β or TNF-α 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 PGE2 synthesis in the exudate where comparable. Although paracetamol significantly increased exudate TNF-α level compared to the control group and NCX 701 group, neither paracetamol, nor NCX701 treatments changed the levels of exudate IL-1β significantly. As expected, paracetamol and NCX 701 showed poor PGE2 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 PGE2 in a similar way. Unlike paracetamol, which increased exudate TNF-α level, NCX 701 had no effect on TNF-α level in the exudates.