Linked Life Data

8595069

Source:http://linkedlifedata.com/resource/pubmed/id/8595069

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1996-4-11
pubmed:abstractText
The superoxide and hydroxyl radical scavenging activities of nimesulide (CAS 51803-78-2) and its main metabolite 4-hydroxynimesulide (CAS 109032-22-6) were investigated by Electron Spin Resonance (ESR) spectroscopy, with the spin trapping technique. Hydroxynimesulide is a good scavenger of both O2 degrees- (IC50 = 40 mumol/l) and HO degree (IC50 = 54.8 mumol/l) radicals, and its high reactivity towards HO degree was confirmed by the rate constant for reaction with HO degree (K = 8.9 x 10(10) mol-1 l s-1) determined by competition kinetic studies with 5,5-dimethyl-l-pyrroline-N-oxide. Nimesulide, which has been shown by ESR to be inactive as a superoxide quencher, has a rate constant of reaction with HO degree slightly greater than that of its metabolite (3.3 x 10(11) mol-1 l s-1). In the HO degree-induced peroxidation of phosphatidylcholine (PC) liposomes, both compounds act as potent preventive antioxidants, but the HO degree entrapping capacity of the parent drug was again greater than that of hydroxynimesulide (IC50 2.12 vs 3.84 mumol/l). The metabolite is also a potent scavenger of the peroxyl radical (ROO degree) in the propagation phase of PC peroxidation (marker conjugated dienes), with an IC50 = 2.67 mumol/l; at 5 mumol/l it induces a lag time in the decomposition of PC hydroperoxides (PC-OOH) into aldehydic products of 40 h longer than in the controls (markers: conjugated dienes and total carbonyl functions). In PC liposomes, in the presence of preformed PC-OOH, the metabolite prevents PC peroxidation stimulated by 5 mumol/l Fe2+, via the Fenton reaction (marker: conjugated dienes), at the micromolar level (IC50 = 17 mumol/l) through an anti-free radical activity and a free iron chelating mechanism. Hydroxynimesulide in fact interacts with Fe2+ ions, giving rise to a strong complex, with a stability constant (log K) estimated to be around 8/9. In addition, hydroxynimesulide efficiently protects ex vivo synovial fluid lipids from the oxidative stress induced by Fe2+/ascorbate, already at 10 mumol/l (marker: thiobarbituric acid reactive substances). These results provide evidence for strong antioxidant and iron-chelating properties of 4-hydroxynimesulide, which can act synergistically with the specific HO degree scavenging activity of the parent drug in preventing and limiting in vivo the free radical-mediated tissue damage in both acute and chronic inflammatory situations.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/4-nitro-2-(4'-hydroxyphenoxy)methane..., http://linkedlifedata.com/resource/pubmed/chemical/Anti-Inflammatory Agents..., http://linkedlifedata.com/resource/pubmed/chemical/Antioxidants, http://linkedlifedata.com/resource/pubmed/chemical/Ascorbic Acid, http://linkedlifedata.com/resource/pubmed/chemical/Free Radical Scavengers, http://linkedlifedata.com/resource/pubmed/chemical/Hydroxyl Radical, http://linkedlifedata.com/resource/pubmed/chemical/Iron, http://linkedlifedata.com/resource/pubmed/chemical/Peroxides, http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylcholines, http://linkedlifedata.com/resource/pubmed/chemical/Reactive Oxygen Species, http://linkedlifedata.com/resource/pubmed/chemical/Sulfonamides, http://linkedlifedata.com/resource/pubmed/chemical/Superoxides, http://linkedlifedata.com/resource/pubmed/chemical/nimesulide
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0004-4172
pubmed:author
pubmed:issnType
Print
pubmed:volume
45
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1102-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Differential inhibition of superoxide, hydroxyl and peroxyl radicals by nimesulide and its main metabolite 4-hydroxynimesulide.
pubmed:affiliation
Istituto Chimico Farmaceutico Tossicologico, University of Milan, Italy.
pubmed:publicationType
Journal Article, In Vitro