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The metabolism of sulindac enhances its scavenging activity against reactive oxygen and nitrogen species

Title
The metabolism of sulindac enhances its scavenging activity against reactive oxygen and nitrogen species
Type
Article in International Scientific Journal
Year
2003
Authors
Fernandes, E
(Author)
FFUP
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Toste, SA
(Author)
Other
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Reis, S
(Author)
FFUP
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Journal
Vol. 35
Pages: 1008-1017
ISSN: 0891-5849
Publisher: Elsevier
Scientific classification
FOS: Medical and Health sciences > Clinical medicine
Other information
Authenticus ID: P-000-EKE
Abstract (EN): Sulindac is a sulfoxide prodrug that, in vivo, is converted to the metabolites sulindac sulfide and sulindac sulfone. It is therapeutically used as an anti-inflammatory and analgesic in the symptomatic treatment of acute and chronic rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis. In addition to its anti-inflammatory properties, sulindac and its metabolites have been shown to have an important role in the prevention of colonic carcinogenesis. Although the inhibition of prostaglandin synthesis constitutes the primary mechanism of action of sulindac, it is well known that reactive oxygen species (ROS) and reactive nitrogen species (RNS) are implicated in the pathophysiology of inflammation and cancer. Thus, the aim of this study was to evaluate the scavenging activity of sulindac and its sulfone and sulfide metabolites for an array of ROS (HO., O-2(.-), and HOCl) and RNS ((NO)-N-. and ONOO-) using in vitro systems. The results we obtained demonstrate that the metabolism of sulindac increases its scavenging activity for all RNS and ROS studied, notably with regard to the scavenging of HOCl. These effects may strongly contribute to the anti-inflammatory and anticarcinogenic efficacy that has been shown for sulindac. (C) 2003 Elsevier Inc.
Language: English
Type (Professor's evaluation): Scientific
No. of pages: 10
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