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Title: Anti-inflammatory and gastrointestinal effects of a novel diclofenac derivative
Authors: Li, L. 
fLee, L.C.
Moore, P.K. 
Rossoni, G.
Sparatore, A.
Del, Soldato P.
Keywords: Diclofenac
Free radicals
Hydrogen sulfide
Issue Date: 2007
Citation: Li, L., fLee, L.C., Moore, P.K., Rossoni, G., Sparatore, A., Del, Soldato P. (2007). Anti-inflammatory and gastrointestinal effects of a novel diclofenac derivative. Free Radical Biology and Medicine 42 (5) : 706-719. ScholarBank@NUS Repository.
Abstract: S-diclofenac (2-[(2,6-dichlorophenyl)amino]benzeneacetic acid 4-(3H-1,2,dithiol-3-thione-5-yl)phenyl ester; ACS 15) is a novel molecule comprising a hydrogen sulfide (H2S)-releasing dithiol-thione moiety attached by an ester linkage to diclofenac. S-diclofenac administration inhibited lipopolysaccharide-induced inflammation (as evidenced by reduced lung and liver myeloperoxidase activity) and caused significantly less gastric toxicity than diclofenac. S-diclofenac did not affect blood pressure or heart rate of the anesthetized rat. S-diclofenac administration downregulated expression of genes encoding enzymes which synthesize nitric oxide, prostanoids, and H2S; reduced plasma IL-1β/TNF-α; and elevated plasma IL-10. Reduced liver NF-κB p65 and AP-1/c-fos DNA-binding activity was also observed. These effects were mimicked in large part by a combination of diclofenac plus an H2S-releasing moiety (ADT-OH). Incubation of S-diclofenac (100 μM) with rat plasma or liver homogenate caused a time-dependent release of H2S, which was inhibited by sodium fluoride (10 mM). Administration of S-diclofenac (47.2 μmol/kg, ip) to conscious rats significantly increased plasma H2S concentration (at 45 min and 6 h). We propose that H2S release from S-diclofenac in vivo contributes to the observed effects. © 2007 Elsevier Inc. All rights reserved.
Source Title: Free Radical Biology and Medicine
ISSN: 08915849
DOI: 10.1016/j.freeradbiomed.2006.12.011
Appears in Collections:Staff Publications

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