S- but not R-enantiomers of flurbiprofen and ibuprofen reduce human microglial and THP-1 cell neurotoxicity.
The protective effects of non-steroidal anti-inflammatory drugs (NSAIDs) in Alzheimer's disease have been demonstrated in multiple epidemiological studies. It has been hypothesized that this is due to their effects on amyloid beta-peptide (Abeta) metabolism, which is independent of the NSAID stereoisoform, rather than inhibition of cyclooxygenase (COX), which is a property of S-enantiomers. We compared the neuroprotective activity of S- and R-enantiomers of flurbiprofen and ibuprofen in a standard assay where secretions from activated human THP-1 or microglial cells are toxic to neuroblastoma SH-SY5Y cells. We found S- but not R-enantiomers to be protective at low concentrations, which is consistent with a COX-dependent mechanism.
Klegeris
Andis
A
Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, Canada V6T 1Z3.
Maguire
John
J
McGeer
Patrick L
PL
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D017077:Culture Media, Conditioned; D004305:Dose-Response Relationship, Drug; D005480:Flurbiprofen / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007052:Ibuprofen / Q000737:chemistry / Q000494:pharmacology*; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D009447:Neuroblastoma / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D013237:Stereoisomerism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D017077:Culture Media, Conditioned; D005480:Flurbiprofen; D007052:Ibuprofen