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Titolo:
Potential adverse effects of cyclooxygenase-2 inhibition: Evidence from animal models of inflammation
Autore:
Colville-Nash, PR; Gilroy, DW;
Indirizzi:
St Bartholomews & Royal London Sch Med & Dent, Dept Expt Pathol, London EC1M 6BQ, England St Bartholomews & Royal London Sch Med & Dent London England EC1M 6BQ nd
Titolo Testata:
BIODRUGS
fascicolo: 1, volume: 15, anno: 2001,
pagine: 1 - 9
SICI:
1173-8804(2001)15:1<1:PAEOCI>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
NONSTEROIDAL ANTIINFLAMMATORY DRUGS; PROSTAGLANDIN-G/H SYNTHASE-1; NITRIC-OXIDE SYNTHASE; SELECTIVE-INHIBITION; INDUCIBLE CYCLOOXYGENASE; EXPRESSION; MICE; RAT; RESPONSES; RECEPTOR;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
51
Recensione:
Indirizzi per estratti:
Indirizzo: Gilroy, DW St Bartholomews & Royal London Sch Med & Dent, Dept Expt Pathol, Charterhouse Sq, London EC1M 6BQ, England St Bartholomews & Royal London Sch Med & Dent Charterhouse Sq London England EC1M 6BQ
Citazione:
P.R. Colville-Nash e D.W. Gilroy, "Potential adverse effects of cyclooxygenase-2 inhibition: Evidence from animal models of inflammation", BIODRUGS, 15(1), 2001, pp. 1-9

Abstract

Cyclooxygenase (COX; prostaglandin H synthase, prostaglandin endoperoxidase) is the key enzyme in the synthesis of the prostaglandin and thromboxane families of eicosanoid mediators, and is the target for the nonsteroidal anti inflammatory drugs (NSAIDs). The identification of an inducible COX isoform, COX-2, and the demonstration of its specific expression at sites of inflammation suggested that it may provide a useful therapeutic target for novel anti-inflammatory drugs. Inhibition of an enzyme that is not expressed in most healthy tissues would potentially avoid most of the adverse effectsassociated with NSAIDs, which target a constitutively expressed isoform, COX-1. The development of novel 'super aspirins' with high selectivity towards the inhibition of COX-2 showed that this hypothesis was well-founded andthat high levels of these drugs could be tolerated without these serious adverse effects. The first two of these new generation NSAIDs, celecoxib androfecoxib, are now in clinical use. More recently, however, concern has been expressed that COX-2 inhibition may in fact have a number of potential, previously hidden, pitfalls. These have arisen from the demonstration that COX-2 induction is not exclusively associated with the onset of an inflammatory reaction, with expression limited to inflammatory sites. In fact, COX-2 is expressed more chronically, andis also seen during the resolution of inflammation and in areas of wound-healing. The application of COX-2-selective inhibitors during these periods has been shown to be deleterious in that resolution of inflammation is delayed, gastric ulcer healing is delayed and, in some patients, ulcers have been shown to progress further to perforation. The suggestion has now been made that, in these situations, COX-2 may help resolve the pathology, perhapsby generating alternative series of prostaglandins such as the cyclopentenone prostaglandins. The finding that, these prostaglandins can affect proteins by direct chemical modifications as well as having their own receptor families has rekindled debate on the deleterious and beneficial effects of prostanoids, and the implications of inhibiting the production of these mediators, in the bodyTherefore, in this review we discuss the role of COX-2 in inflammation andthe potential adverse effects of its inhibition.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/07/20 alle ore 12:57:26