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Effect of S-diclofenac, a novel hydrogen sulfide releasing derivative, on carrageenan-induced hindpaw oedema formation in the rat.
Eur J Pharmacol. 2007 Aug 13; 569(1-2):149-54.EJ

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 (H(2)S) 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 (ED(30), 14.2+/-0.6 micromol/kg) was more potent (P<0.05) than diclofenac (ED(30), 39.3+/-1.4 micromol/kg) as an inhibitor both of hindpaw swelling and in reducing the carrageenan-evoked rise in hindpaw myeloperoxidase activity reflecting tissue neutrophil infiltration (ED(50)s of 12.0+/-2.1 micromol/kg and 21.9+/-2.0 micromol/kg). Intraplantar carrageenan injection also significantly (P<0.05) increased hindpaw concentrations of prostaglandin E(2) (PGE(2)), nitrite/nitrate and H(2)S synthesizing activity measured at 6 h. Both S-diclofenac and diclofenac pretreatment reduced the carrageenan-induced rise in hindpaw PGE(2), nitrite/nitrate and H(2)S synthesizing activity. Whilst treatment with either drug produced similar inhibition of hindpaw PGE(2) and H(2)S 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 H(2)S at the inflamed site. These data provide evidence for an anti-inflammatory effect of H(2)S.

Authors+Show Affiliations

Department of Pharmacology, Cardiovascular Biology Research Group, Yong Loo Lin School of Medicine, National University of Singapore, 18 Medical Drive, Singapore, 117597, Singapore.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17553487

Citation

Sidhapuriwala, Jenab, et al. "Effect of S-diclofenac, a Novel Hydrogen Sulfide Releasing Derivative, On Carrageenan-induced Hindpaw Oedema Formation in the Rat." European Journal of Pharmacology, vol. 569, no. 1-2, 2007, pp. 149-54.
Sidhapuriwala J, Li L, Sparatore A, et al. Effect of S-diclofenac, a novel hydrogen sulfide releasing derivative, on carrageenan-induced hindpaw oedema formation in the rat. Eur J Pharmacol. 2007;569(1-2):149-54.
Sidhapuriwala, J., Li, L., Sparatore, A., Bhatia, M., & Moore, P. K. (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), 149-54.
Sidhapuriwala J, et al. Effect of S-diclofenac, a Novel Hydrogen Sulfide Releasing Derivative, On Carrageenan-induced Hindpaw Oedema Formation in the Rat. Eur J Pharmacol. 2007 Aug 13;569(1-2):149-54. PubMed PMID: 17553487.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of S-diclofenac, a novel hydrogen sulfide releasing derivative, on carrageenan-induced hindpaw oedema formation in the rat. AU - Sidhapuriwala,Jenab, AU - Li,Ling, AU - Sparatore,Anna, AU - Bhatia,Madhav, AU - Moore,Philip K, Y1 - 2007/05/13/ PY - 2007/01/16/received PY - 2007/03/22/revised PY - 2007/05/03/accepted PY - 2007/6/8/pubmed PY - 2007/10/27/medline PY - 2007/6/8/entrez SP - 149 EP - 54 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 569 IS - 1-2 N2 - 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 (H(2)S) 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 (ED(30), 14.2+/-0.6 micromol/kg) was more potent (P<0.05) than diclofenac (ED(30), 39.3+/-1.4 micromol/kg) as an inhibitor both of hindpaw swelling and in reducing the carrageenan-evoked rise in hindpaw myeloperoxidase activity reflecting tissue neutrophil infiltration (ED(50)s of 12.0+/-2.1 micromol/kg and 21.9+/-2.0 micromol/kg). Intraplantar carrageenan injection also significantly (P<0.05) increased hindpaw concentrations of prostaglandin E(2) (PGE(2)), nitrite/nitrate and H(2)S synthesizing activity measured at 6 h. Both S-diclofenac and diclofenac pretreatment reduced the carrageenan-induced rise in hindpaw PGE(2), nitrite/nitrate and H(2)S synthesizing activity. Whilst treatment with either drug produced similar inhibition of hindpaw PGE(2) and H(2)S 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 H(2)S at the inflamed site. These data provide evidence for an anti-inflammatory effect of H(2)S. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/17553487/Effect_of_S_diclofenac_a_novel_hydrogen_sulfide_releasing_derivative_on_carrageenan_induced_hindpaw_oedema_formation_in_the_rat_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(07)00553-5 DB - PRIME DP - Unbound Medicine ER -