![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 55, Issue 4, 753-760, April 1999
Department of Pharmacology, Uriach Research Center, Barcelona,
Spain (A.F.deA., F.C., A.M., M.M., J.G.-R., J.F.); and
Instituto de
Biología y Genética Molecular, Consejo Superior de
Investigaciones Científicas, Facultad de Medicina, Valladolid,
Spain (Y.B., A.A.)
The therapeutic potential of drugs that block the induction of
cyclooxygenase-2 has been emphasized. When two 4-trifluoromethyl salicylate derivatives [2-acetoxy-4-trifluoromethyl-benzoic acid (triflusal) and its deacetylated metabolite
2-hydroxy-4-trifluoromethylbenzoic acid (HTB)] were compared with
aspirin and sodium salicylate as cyclooxygenase-2 (COX-2) inhibitors,
we observed that in bacterial lipopolysaccharide-activated human blood,
triflusal, aspirin, and HTB, but not sodium salicylate, inhibited
COX-2-mediated prostaglandin E2 (PGE2)
production (IC50 = 0.16, 0.18, 0.39, and >10 mM,
respectively). However, only triflusal and aspirin inhibited purified
COX-2 enzyme. To test this apparent discrepancy, we realized that HTB
and triflusal (but neither aspirin nor salicylate) produced a
concentration-dependent inhibition of COX-2 protein expression in
peripheral human mononuclear cells. This observation was further
confirmed in a rat air pouch model in vivo, in which both aspirin and
triflusal inhibited PGE2 production (ID50 = 18.9 and 11.4 mg/kg p.o., respectively) but only triflusal-treated
animals showed a decrease in COX-2 expression. This different behavior
may be, at least in part, due to the ability of HTB and triflusal to
block the activation of the transcription factor nuclear factor-
B to
a higher extent than aspirin and sodium salicylate. Thus, in addition
to inhibiting the COX-2 activity at therapeutic concentrations,
triflusal is able to block through its metabolite HTB the expression of
new enzyme, and hence the resumption of PGE2
synthesis. Triflusal and HTB may exert beneficial effects in processes
in which de novo COX-2 expression is involved and, in a broader sense,
in pathological situations in which genes under nuclear factor-B
control are up-regulated.
This article has been cited by other articles:
|
|
 |
|
  J.-M. Fernandez-Real, A. Lopez-Bermejo, A.-B. Ropero, S. Piquer, A. Nadal, J. Bassols, R. Casamitjana, R. Gomis, E. Arnaiz, I. Perez, et al. Salicylates Increase Insulin Secretion in Healthy Obese Subjects J. Clin. Endocrinol. Metab., July 1, 2008; 93(7): 2523 - 2530. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Planavila, R. Rodriguez-Calvo, A. F. de Arriba, R. M. Sanchez, J. C. Laguna, M. Merlos, and M. Vazquez-Carrera Inhibition of Cardiac Hypertrophy by Triflusal (4-Trifluoromethyl Derivative of Salicylate) and Its Active Metabolite Mol. Pharmacol., April 1, 2006; 69(4): 1174 - 1181. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Matsuda, Y. Hattori, S. Jesmin, and S. Gando Nuclear Factor-{kappa}B Decoy Oligodeoxynucleotides Prevent Acute Lung Injury in Mice with Cecal Ligation and Puncture-Induced Sepsis Mol. Pharmacol., April 1, 2005; 67(4): 1018 - 1025. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Matias-Guiu, J. M. Ferro, J. Alvarez-Sabin, F. Torres, M. D. Jimenez, A. Lago, T. Melo, and D. C. Tong Comparison of Triflusal and Aspirin for Prevention of Vascular Events in Patients After Cerebral Infarction: The TACIP Study: A Randomized, Double-Blind, Multicenter Trial * Can Aspirin Ever Be Surpassed for Stroke Prevention? Stroke, April 1, 2003; 34(4): 840 - 848. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Acarin, B. Gonzalez, and B. Castellano Decrease of Proinflammatory Molecules Correlates With Neuroprotective Effect of the Fluorinated Salicylate Triflusal After Postnatal Excitotoxic Damage Stroke, October 1, 2002; 33(10): 2499 - 2505. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Fernandez, M. Renedo, C. Garcia-Rodriguez, and M. Sanchez Crespo Activation of Monocytic Cells Through Fc{gamma} Receptors Induces the Expression of Macrophage-Inflammatory Protein (MIP)-1{alpha}, MIP-1{beta}, and RANTES J. Immunol., September 15, 2002; 169(6): 3321 - 3328. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Acarin, B. Gonzalez, and B. Castellano Triflusal Posttreatment Inhibits Glial Nuclear Factor-{kappa}B, Downregulates the Glial Response, and Is Neuroprotective in an Excitotoxic Injury Model in Postnatal Brain Stroke, October 1, 2001; 32(10): 2394 - 2402. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.M Cruz-Fernandez, L Lopez-Bescos, D Garcia-Dorado, V Lopez Garcia-Aranda, A Cabades, L Martin-Jadraque, J.A Velasco, A Castro-Beiras, F Torres, F Marfil, et al. Randomized comparative trial of triflusal and aspirin following acute myocardial infarction Eur. Heart J., March 2, 2000; 21(6): 457 - 465. [Abstract] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
