Hydrogen sulfide‐releasing NSAIDs attenuate neuroinflammation induced by microglial and astrocytic activation

• DOI: 10.1002/glia.20905
• Publication Date: 2009-06-18T17:42:36Z
• Authors: Moonhee Lee; Anna Sparatore; Piero Del Soldato; Edith Mcgeer; Patrick L. McGeer
• Keywords: Proinflammatory cytokine

Abstract Endogenously generated hydrogen sulfide (H 2 S) may have multiple functions in brain. It has been shown that H S attenuates the expression of pro‐inflammatory cytokines by lipopolysaccharide (LPS)‐activated microglia. Here we demonstrate a neuroprotective effect NaSH and three S‐releasing compounds, ADT‐OH, S‐diclofenac, S‐aspirin. When activated LPS γ‐interferon, human microglia THP‐1 cells release materials are toxic to neuroblastoma SH‐SY5Y cells. These phenomena also occur with γ‐interferon‐stimulated astroglia U118 these cell types pretreated aspirin, diclofenac, NASH, or supernatants significantly less toxic. they treated NSAID‐H hybrid molecules S‐diclofenac S‐aspirin, which here referred as S‐NSAIDs, there is significant enhancement protection. The concentration incubation time dependent. Such pretreatment reduces proinflammatory mediators TNFα, IL‐6, nitric oxide. compounds without when applied directly data suggest releasing antiinflammatory properties be candidates for treating neurodegenerative disorders prominent neuroinflammatory component such Alzheimer disease Parkinson disease. © 2009 Wiley‐Liss, Inc.