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Title: Effect of S-diclofenac, a novel hydrogen sulfide releasing derivative, on carrageenan-induced hindpaw oedema formation in the rat
Authors: Sidhapuriwala, J. 
Li, L. 
Bhatia, M. 
Moore, P.K. 
Sparatore, A.
Keywords: Diclofenac
Hydrogen sulfide
Issue Date: 2007
Citation: Sidhapuriwala, J., Li, L., Bhatia, M., Moore, P.K., Sparatore, A. (2007). Effect of S-diclofenac, a novel hydrogen sulfide releasing derivative, on carrageenan-induced hindpaw oedema formation in the rat. European Journal of Pharmacology 569 (1-2) : 149-154. ScholarBank@NUS Repository.
Abstract: S-diclofenac (2-[(2,6-dichlorophenyl)amino]benzeneacetic acid 4-(3H-1,2-dithiole-3-thione-5-yl)-phenyl ester) is a novel derivative of diclofenac which, in vivo, undergoes enzymatic cleavage of its ester linkage to release hydrogen sulfide (H2S) along with the parent moiety, diclofenac. In this study the anti-inflammatory activity of S-diclofenac and diclofenac was studied in a carrageenan-evoked hindpaw oedema model in the rat. Drugs or vehicle were administered 3 h before carrageenan. Both drugs produced a dose-dependent anti-inflammatory effect in this model. However, S-diclofenac (ED30, 14.2 ± 0.6 μmol/kg) was more potent (P < 0.05) than diclofenac (ED30, 39.3 ± 1.4 μmol/kg) as an inhibitor both of hindpaw swelling and in reducing the carrageenan-evoked rise in hindpaw myeloperoxidase activity reflecting tissue neutrophil infiltration (ED50s of 12.0 ± 2.1 μmol/kg and 21.9 ± 2.0 μmol/kg). Intraplantar carrageenan injection also significantly (P < 0.05) increased hindpaw concentrations of prostaglandin E2 (PGE2), nitrite/nitrate and H2S synthesizing activity measured at 6 h. Both S-diclofenac and diclofenac pretreatment reduced the carrageenan-induced rise in hindpaw PGE2, nitrite/nitrate and H2S synthesizing activity. Whilst treatment with either drug produced similar inhibition of hindpaw PGE2 and H2S synthesizing activity - S-diclofenac more effectively reduced hindpaw nitrite/nitrate concentration than did diclofenac. It is proposed that the enhanced anti-inflammatory effect of S-diclofenac relates to its ability to release H2S at the inflamed site. These data provide evidence for an anti-inflammatory effect of H2S. © 2007 Elsevier B.V. All rights reserved.
Source Title: European Journal of Pharmacology
ISSN: 00142999
DOI: 10.1016/j.ejphar.2007.05.003
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