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Hydrogen sulfide‐releasing NSAIDs attenuate neuroinflammation induced by microglial and astrocytic activation
Author(s) -
Lee Moonhee,
Sparatore Anna,
Del Soldato Piero,
Mcgeer Edith,
McGeer Patrick L.
Publication year - 2009
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.20905
Subject(s) - neuroinflammation , neuroprotection , microglia , pharmacology , proinflammatory cytokine , nitric oxide , lipopolysaccharide , aspirin , biology , chemistry , inflammation , medicine , immunology , biochemistry , endocrinology
Endogenously generated hydrogen sulfide (H 2 S) may have multiple functions in brain. It has been shown that H 2 S attenuates the expression of pro‐inflammatory cytokines by lipopolysaccharide (LPS)‐activated microglia. Here we demonstrate a neuroprotective effect of NaSH and three H 2 S‐releasing compounds, ADT‐OH, S‐diclofenac, and S‐aspirin. When activated by LPS and γ‐interferon, human microglia and THP‐1 cells release materials that are toxic to human neuroblastoma SH‐SY5Y cells. These phenomena also occur with γ‐interferon‐stimulated human astroglia and U118 cells. When these cell types are pretreated with aspirin, diclofenac, NASH, or ADT‐OH, the supernatants are significantly less toxic. When they are treated with the NSAID‐H 2 S hybrid molecules S‐diclofenac and S‐aspirin, which are here referred to as S‐NSAIDs, there is a significant enhancement of the protection. The effect is concentration and incubation time dependent. Such pretreatment also reduces the release of the proinflammatory mediators TNFα, IL‐6, and nitric oxide. The H 2 S‐releasing compounds are without effect when applied directly to SH‐SY5Y cells. These data suggest that hybrid H 2 S releasing compounds have significant antiinflammatory properties and may be candidates for treating neurodegenerative disorders that have a prominent neuroinflammatory component such as Alzheimer disease and Parkinson disease. © 2009 Wiley‐Liss, Inc.