Synergistic anti-inflammatory interaction between meloxicam and aminoguanidine hydrochloride in carrageenan-induced acute inflammation in rats

Interaction studies with inducible nitric oxide synthase (NOS) and cyclooxygenase-2 (COX-2) inhibitor have been conducted to assess the nature of interaction and the possible therapeutic advantage. The interaction between meloxicam - a selective COX-2 inhibitor - and aminoguanidine hydrochloride - a selective iNOS inhibitor - was examined in carrageenan-induced paw edema in rats. Appropriate statistical method was applied to detect the nature of anti-inflammatory interaction. Different doses of meloxicam (1, 3, 10 and 30 mg/kg) or aminoguanidine hydrochloride (10, 30, 100 and 300 mg/kg) were administered orally to adult male albino rats. Higher doses of meloxicam (3, 10 and 30 mg/kg) showed statistically significant anti-inflammatory effect. However, aminoguanidine hydrochloride did not show any anti-inflammatory activity. Combination of sub-threshold dose of meloxicam (1 mg/kg) with increasing doses of aminoguanidine hydrochloride (30, 100 and 300 mg/kg) resulted in synergistic anti-inflammatory effect. Combined therapy with sub-threshold dose of aminoguanidine hydrochloride (30 mg/kg) with increasing doses of meloxicam (1, 3, 10 and 30 mg/kg) also resulted in synergistic anti-inflammatory effect. The possible mechanism of interaction could be the stimulation of COX-2 activity by nitric oxide (NO) by combining with heme component. These results suggest that co-administration of meloxicam and aminoguanidine hydrochloride may be an alternative in clinical control of inflammation. (c) 2005 Elsevier Inc. All rights reserved.