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 mol. 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-1/TNF-; and elevated plasma IL-10. Reduced liver NF-B p65 and AP-1/c-fos DNA-binding activity was also obsd. These effects were mimicked in large part by a combination of diclofenac plus an H2S-releasing moiety (ADT-OH). Incubation of S-diclofenac (100 M) 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 mol/kg, i.p.) to conscious rats significantly increased plasma H2S concn. (at 45 min and 6 h). We propose that H2S release from S-diclofenac in vivo contributes to the obsd. effects

Anti-inflammatory and gastrointestinal effects of a novel diclofenac derivative / L. Li, G.B. Rossoni, A.C. Sparatore, L.C. Lee, P. Del Soldato, P.K. Moore. - In: FREE RADICAL BIOLOGY & MEDICINE. - ISSN 0891-5849. - 42:5(2007), pp. 706-719.

Anti-inflammatory and gastrointestinal effects of a novel diclofenac derivative

G.B. Rossoni
Secondo
;
A.C. Sparatore;
2007

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 mol. 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-1/TNF-; and elevated plasma IL-10. Reduced liver NF-B p65 and AP-1/c-fos DNA-binding activity was also obsd. These effects were mimicked in large part by a combination of diclofenac plus an H2S-releasing moiety (ADT-OH). Incubation of S-diclofenac (100 M) 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 mol/kg, i.p.) to conscious rats significantly increased plasma H2S concn. (at 45 min and 6 h). We propose that H2S release from S-diclofenac in vivo contributes to the obsd. effects
Settore CHIM/08 - Chimica Farmaceutica
2007
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T38-4MKCGXH-4&_user=1080510&_coverDate=03%2F01%2F2007&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000051355&_version=1&_urlVersion=0&_userid=1080510&md5=d0bb45a64ed97de382f8d6ac9884557b
Article (author)
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/32354
Citazioni
  • ???jsp.display-item.citation.pmc??? 100
  • Scopus 300
  • ???jsp.display-item.citation.isi??? 280
social impact