Potentiation of diclofenac-induced anti-inflammatory response by aminoguanidine in carrageenan-induced acute inflammation in rats: The role of nitric oxide

Objective: To investigate whether aminoguanidine (AG) treatment enhances the anti-inflammatory effect of diclofenac in an acute inflammation model in rats. Material and methods: In 48 rats carrageenan-induced paw edema was used as an acute inflammation model. Inflammatory activity was assessed at 1.5, 3 and 6 h after subplanter injection of carrageenan (0.1 ml of a 1% solution in 0.85% saline). The anti-inflammatory effect of diclofenac (25 mg/kg, i.p.) was studied in comparison to that of the selective inducible nitric oxide synthase (iNOS) inhibitor, AG, and of nitric oxide donor, sodium nitroprusside (SNP). Results: AG, failed to inhibit inflammation during the first 3 It following carrageenan administration, but caused a slight, although statistically insignificant inhibition at 6 It. Diclofenac significantly reduced the carrageenan-induced edema in rat paw at all the time points studied. Administration of diclofenac after AG pretreatment caused significant (P < 0.001) reduction in edema that was double that of diclofenac alone 6 It after carrageenan injection. Administration of SNP as a single dose after AG pretreatment prevented any potentiation of anti-inflammatory response that was observed in the case of AG combined with diclofenac treatment. Conclusion: These results show that AG markedly potentiates the anti-inflammatory activity of diclofenac at 6 h and this potentiation effect is nitric oxide-dependent.