Abstract

The present study was designed to evaluate anti-inflammatory effects of N-acetylaspartylglutamate (NAAG), as a presynaptic mGlu3 receptor agonist on carrageenan-induced paw edema in rats. NAAG was administered intraperitoneally (10 mg/kg) 20 min before the intraplantar injection of the carrageenan. Neutrophil infiltration (MPO activity), lipid peroxidation (MDA assay), free radical scavenging activity (SOD and GPx assay), IL-1β, TNF-α, and PGE2 levels were assessed in the paw tissue of the NAAG treated rats when compared with the control rats. Results showed that intraperitoneal administration of the NAAG significantly reduced maximum paw volume by 52.5% and total inflammatory response by 56.9%, 4 h after the induction of inflammation (p < 0.001). Injection of the NAAG resulted in a marked reduction of MPO activity in the inflamed paw by 80.2% in comparison with the control group (p < 0.01). Moreover, NAAG not only reduced the MDA levels to 54.3%, but also enhanced the SOD activity in the NAAG treated group up to 25% when compared with the control group. Levels of IL-1β, TNF-α, and PGE2 in the NAAG treated group were respectively reduced by 72.4, 23, and 13%. Generally, the NAAG activates mGlu3 receptors on sensory neurons, resulting in reduction of cAMP levels and inhibition of glutamate release. Overall, our results suggest that NAAG activation of mGlu3 receptors on the sensory neurons negates the effects of PGE2 and reduces the sensory neuron communication of inflammation.

Key words: N-acetylaspartylglutamate, glutamate, inflammation, carrageenan, cytokines.