Synergistic anti-inflammatory interaction between meloxicam and aminoguanidine hydrochloride in carrageenan-induced acute inflammation in rats.
Interaction studies with inducible nitric oxide synthase (iNOS) 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.
Dudhgaonkar
Shailesh P
SP
Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, U.P. - 243 122 India.
Tandan
Surendra K
SK
Bhat
Abdul Shakoor
AS
Jadhav
Sachin H
SH
Kumar
Dinesh
D
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002351:Carrageenan; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005528:Foot / Q000473:pathology; D006146:Guanidines / Q000494:pharmacology*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D000077239:Meloxicam; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors*; D051381:Rats; D013843:Thiazines / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D004791:Enzyme Inhibitors; D006146:Guanidines; D013843:Thiazines; D013844:Thiazoles; D002351:Carrageenan; D052247:Nitric Oxide Synthase Type II; C004479:pimagedine; D000077239:Meloxicam