Abstract
S-diclofenac (2-[(2,6-dichlorophenyl)amino]benzeneacetic acid 4-(3
H-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
2S) 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 μmol/kg) was more potent (
P
<
0.05) than diclofenac (ED
30, 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 (ED
50s 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 E
2 (PGE
2), nitrite/nitrate and H
2S 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
2S synthesizing activity. Whilst treatment with either drug produced similar inhibition of hindpaw PGE
2 and H
2S 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
2S at the inflamed site. These data provide evidence for an anti-inflammatory effect of H
2S.