Interaction of allopurinol and non-steroidal anti-inflammatory drugs on the carrageenan-induced rat paw edema

OBJECTIVE: To find out the effect of combining allopurinol with non-steroidal anti-inflammatory drugs on carrageenan-induced rat paw edema.

METHODS: The study was carried out at the College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia, over the period 1999 to 2000. Male wistar rats were randomly divided into 12-16 rats in each group. Edema was induced by subplantar injection of 0.1 ml of carrageenan (10 mg/ml) and the resulting edema volume was measured by plethysmograph, 3 hours after the injections. Saline of 0.9% (0.1 ml/100 g) was administered to the first group serving as control. The second and third groups received variable concentration of allopurinol (12.5, 25, 50 mg/kg) and tenoxicam (0.0625, 0.125, 0.25 mg/kg) 30 minutes before carrageenan injection. The fourth group received a combination of tenoxicam and allopurinol. Similar procedures were carried out with respect to diclofenac at 1.25, 2.5, 5.0 mg/kg and indomethacin at 0.25, 0.5, 1.0 mg/kg. The activities of the drugs were expressed as percentage inhibition of edema.

RESULTS: Pre-treatment of the rats with the 4 drugs individually resulted in dose-dependent reduction of volume of paw edema. The combination of allopurinol and diclofenac acted synergistically to reduce edema. A similar synergistic action was obtained when allopurinol was combined with indomethacin. By contrast, tenoxicam-allopurinol combination resulted in antagonistic action and produced an effect on edema, which was less than their individual inhibitory action.

CONCLUSION: Combining allopurinol with either diclofenac or indomethacin produced synergistic inhibitory action on rat's paw edema. However, tenoxicam, when combined with allopurinol, produced antagonism.