NO-flurbiprofen attenuates excitotoxin-induced brain inflammation, and releases nitric oxide in the brain.
Brain inflammation underlies the pathogenesis of Alzheimer's disease (AD) and nonsteroidal anti-inflammatory drug therapy may delay the onset of AD. We investigated, in vivo, the effects of NO-flurbiprofen on brain inflammation in rats injected with quisqualic acid into the nucleus basalis and on the release of nitric oxide from the drug in naive rat brains. We showed that the excitotoxin-induced microglia reaction, the expression of inducible nitric oxide synthase-positive cells and the production of interleukin-1beta and prostaglandin-E2 in the injected area were attenuated by the NO-flurbiprofen (15 mg/kg, p.o.) treatment. An oral administration of NO-flurbiprofen (25, 50 and 100 mg/kg) to naive rats was followed by significant increases in cortical nitrite levels. This drug may have important therapeutic implications for the treatment of AD.
Prosperi
C
C
Department of Pharmacology, University of Florence, Italy.
Scali
C
C
Pepeu
G
G
Casamenti
F
F
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D004660:Encephalitis / Q000139:chemically induced* / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism; D018690:Excitatory Amino Acid Agonists; D005480:Flurbiprofen / Q000494:pharmacology* / Q000627:therapeutic use; D016166:Free Radical Scavengers / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009498:Neurotoxins / Q000009:adverse effects*; D009569:Nitric Oxide / Q000494:pharmacology* / Q000627:therapeutic use; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D016318:Quisqualic Acid; D051381:Rats; D017208:Rats, Wistar
D000894:Anti-Inflammatory Agents, Non-Steroidal; D018690:Excitatory Amino Acid Agonists; D016166:Free Radical Scavengers; D009498:Neurotoxins; D009569:Nitric Oxide; D005480:Flurbiprofen; D016318:Quisqualic Acid; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat