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Title: GYY4137, a novel hydrogen sulfide-releasing molecule, protects against endotoxic shock in the rat
Authors: Li, L.
Moore, P.K.
Salto-Tellez, M. 
Tan, C.-H. 
Whiteman, M.
Keywords: Cytokines
Hydrogen sulfide
Nitric oxide
Septic shock
Issue Date: 2009
Citation: Li, L., Moore, P.K., Salto-Tellez, M., Tan, C.-H., Whiteman, M. (2009). GYY4137, a novel hydrogen sulfide-releasing molecule, protects against endotoxic shock in the rat. Free Radical Biology and Medicine 47 (1) : 103-113. ScholarBank@NUS Repository.
Abstract: GYY4137 (morpholin-4-ium-4-methoxyphenyl(morpholino) phosphinodithioate) is a slow-releasing hydrogen sulfide (H2S) donor. Administration of GYY4137 (50 mg/kg, iv) to anesthetized rats 10 min after lipopolysaccharide (LPS; 4 mg/kg, iv) decreased the slowly developing hypotension. GYY4137 inhibited LPS-induced TNF-α production in rat blood and reduced the LPS-evoked rise in NF-κB activation, inducible nitric oxide synthase/cyclooxygenase-2 expression, and generation of PGE2 and nitrate/nitrite in RAW 264.7 macrophages. GYY4137 (50 mg/kg, ip) administered to conscious rats 1 or 2 h after (but not 1 h before) LPS decreased the subsequent (4 h) rise in plasma proinflammatory cytokines (TNF-α, IL-1β, IL-6), nitrite/nitrate, C-reactive protein, and L-selectin. GYY4137 administration also decreased the LPS-evoked increase in lung myeloperoxidase activity, increased plasma concentration of the anti-inflammatory cytokine IL-10, and decreased tissue damage as determined histologically and by measurement of plasma creatinine and alanine aminotransferase activity. Time-expired GYY4137 (50 mg/kg, ip) did not affect the LPS-induced rise in plasma TNF-α or lung myeloperoxidase activity. GYY4137 also decreased the LPS-mediated upregulation of liver transcription factors (NF-κB and STAT-3). These results suggest an anti-inflammatory effect of GYY4137. The possibility that GYY4137 and other slow-releasing H2S donors exert anti-inflammatory activity in other models of inflammation and in humans warrants further study. © 2009 Elsevier Inc. All rights reserved.
Source Title: Free Radical Biology and Medicine
ISSN: 08915849
DOI: 10.1016/j.freeradbiomed.2009.04.014
Appears in Collections:Staff Publications

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