RGD Reference Report - GYY4137, a novel hydrogen sulfide-releasing molecule, protects against endotoxic shock in the rat. - Rat Genome Database

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GYY4137, a novel hydrogen sulfide-releasing molecule, protects against endotoxic shock in the rat.

Authors: Li, L  Salto-Tellez, M  Tan, CH  Whiteman, M  Moore, PK 
Citation: Li L, etal., Free Radic Biol Med. 2009 Jul 1;47(1):103-13. Epub 2009 Apr 15.
RGD ID: 5685700
Pubmed: PMID:19375498   (View Abstract at PubMed)
DOI: DOI:10.1016/j.freeradbiomed.2009.04.014   (Journal Full-text)

GYY4137 (morpholin-4-ium-4-methoxyphenyl(morpholino) phosphinodithioate) is a slow-releasing hydrogen sulfide (H(2)S) 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-alpha production in rat blood and reduced the LPS-evoked rise in NF-kappaB activation, inducible nitric oxide synthase/cyclooxygenase-2 expression, and generation of PGE(2) 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-alpha, IL-1beta, 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-alpha or lung myeloperoxidase activity. GYY4137 also decreased the LPS-mediated upregulation of liver transcription factors (NF-kappaB and STAT-3). These results suggest an anti-inflammatory effect of GYY4137. The possibility that GYY4137 and other slow-releasing H(2)S donors exert anti-inflammatory activity in other models of inflammation and in humans warrants further study.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
toxic shock syndrome  ISOSell (Rattus norvegicus)5685700; 5685700protein:increased expression:plasmaRGD 
toxic shock syndrome  IEP 5685700protein:increased expression:plasmaRGD 

Objects Annotated

Genes (Rattus norvegicus)
Sell  (selectin L)

Genes (Mus musculus)
Sell  (selectin, lymphocyte)

Genes (Homo sapiens)
SELL  (selectin L)


Additional Information