Inhibitory effects of novel tetrahydropyridine derivatives on nitric oxide and reactive oxygen species production in glioma cells

The immune response in the central nervous system involves the degeneration of neurological tissue. The therapeutic use of nonsteroidal anti-inflammatory agents (NSAIDs) can be effective in reducing inflammation and associated neurodegeneration. The current study was designed to examine the effects of previously synthesized N-(substituted benzoylamino)-4-ethyl-1,2,3,6-tetrahydropyridines (THPs) on free radical and nitric oxide (NO) generation in C6 glioma cells activated with bacterial endotoxin [lipopolysaccharide (LPS): Escherichia coli 0111:B4] and interferon-γ. Stimulated C6 cells exhibited elevated iNOS protein expression, an increase of reactive oxygen species and NO2−. All parameters were attenuated significantly by indomethacin and various THPs (4-Ome, 3-CF3, 4-Me, 4-Et, 4-t-butyl, and 4-n-butyl). The results indicate a possible role for THP derivatives as anti-inflammatory agents. Drug Dev. Res. 61:189–196, 2004. © 2004 Wiley-Liss, Inc.