Disease relevance of Triflusal

• CONCLUSION:Triflusal and aspirin have similar efficacy in preventing further cardiovascular events after acute myocardial infarction, but triflusal showed a more favourable safety profile [1].
• Assessment of the effects of triflusal in pressure overload-induced cardiac hypertrophy by aortic banding resulted in a significant reduction in the ratio of heart weight to body weight and in a reduction of the mRNA levels of the cardiac hypertrophy markers ANF and alpha-actinin compared with untreated banded rats [2].
• Triflusal, compared with placebo for 6 months, significantly reduced the incidence of nonfatal myocardial infarction in patients with unstable angina [3].
• Triflusal : a review of its use in cerebral infarction and myocardial infarction, and as thromboprophylaxis in atrial fibrillation [4].
• In addition, triflusal plus moderate-intensity anticoagulation has demonstrated efficacy when used as thromboprophylaxis in atrial fibrillation [4].

Psychiatry related information on Triflusal

• OBJECTIVE: Triflusal has been shown to exert neuroprotective effects by downregulating molecules considered responsible for the development of Alzheimer's disease (AD) [5].
• Aspirin, triflusal and Ginkgo biloba extract were associated with some stabilization of dementia progression, perhaps due to their antiplatelet effects [6].

High impact information on Triflusal

• RNase protection assays showed that 2-acetoxy-4-trifluoromethylbenzoic acid (triflusal) inhibited, in a dose-dependent manner, mRNA expression of several cytokine genes, most of which are NFAT-regulated and cyclosporin A (CsA)-sensitive [7].
• Transactivation experiments performed with several NFAT-dependent and AP-1-dependent reporter genes showed that triflusal strongly inhibited NFAT-dependent transcription at concentrations as low as 0.25 mM [7].
• These results indicate that triflusal, a drug with a well characterized pharmacological and safety profile currently used as antiplatelet, inhibits cardiomyocyte growth by interfering with the NF-kappaB signaling pathway through a post-transcriptional mechanism involving reduced-proteosome degradation of IkappaBalpha [2].
• It is noteworthy that banded rats treated with oral triflusal, compared with untreated rats, showed enhanced protein levels of IkappaBalpha, which forms a cytoplasmic inactive complex with the p65-p50 heterodimeric complex [2].
• Overall, both drugs were well tolerated, although there was a trend towards fewer bleeding episodes with triflusal; significantly fewer central nervous system bleeding episodes were observed in triflusal-treated patients (0.27% vs. 0.97%; P = 0.033) [1].

Chemical compound and disease context of Triflusal

• Regarding safety, three patients in triflusal group reported at least one hemorrhage, compared to 10 in acenocoumarol group (P=0.048) [8].
• Effects of triflusal and acetylsalicylic acid on microthrombi formation in experimental brain ischemia [9].
• MAIN RESULTS: (1) Aspirin versus triflusal: five studies enrolled patients with stroke or transient ischemic attack (TIA) (4 trials; 2944 patients; followed for 6 to 47 months) or AMI (one trial; 2275 patients; followed for 35 days) [10].

Biological context of Triflusal

• In T2DM triflusal causes a profound inhibition of platelet TXA(2) biosynthesis in vivo, acting on different targets involved in the platelet-endothelial cell interactions [11].
• 4. In keeping with their inhibitory effect on IkappaBbeta degradation in the cell lysates, both HTB and triflusal inhibited the phosphorylation of GST-IkappaBbeta elicited by TNF-alpha, without affecting the phosphorylation of GST-IkappaBalpha [12].
• After triflusal treatment, the neutrophils demonstrated a higher ability to prevent ADP-induced platelet aggregation [13].
• In contrast, triflusal treated rats showed a drastic downregulation of neuronal and glial NF-kappaB, both in the number of labelled cells and in the intensity of staining [14].
• Triflusal decreased cell death in rat brain slices subjected to reoxygenation after anoxia by 21%, 42% and 47% with 1, 10 and 50 mg/kg/day, respectively [15].

Anatomical context of Triflusal

• Therefore, the whole molecule of triflusal is needed to stimulate NO production by neutrophils [16].
• Effects of triflusal in patients with prosthetic heart valves [17].
• Influence of triflusal on platelet activation after coronary artery bypass graft [18].
• Access of HTB, main metabolite of triflusal, to cerebrospinal fluid in healthy volunteers [5].
• CONCLUSIONS: The results suggest that triflusal and aspirin appear to be equally neuroprotective against middle cerebral artery occlusion-induced cerebral ischemia [19].

Associations of Triflusal with other chemical compounds

• 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 [20].
• Inhibition of cyclooxygenase-2 expression by 4-trifluoromethyl derivatives of salicylate, triflusal, and its deacetylated metabolite, 2-hydroxy-4-trifluoromethylbenzoic acid [20].
• 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 [20].
• Our results show that, in the presence of neutrophils, triflusal exerts an antiplatelet effect greater than that of acetylsalicylic acid, demonstrating a more powerful stimulation of the NO/cGMP system [16].
• Effects of triflusal on oxidative stress, prostaglandin production and nitric oxide pathway in a model of anoxia-reoxygenation in rat brain slices [15].

Gene context of Triflusal

• The closure time in the presence of collagen plus ADP (Coll/ADP-CT), ICAM-1, VCAM-1, and NO(2)(-)+NO(3)(-) were not modified either by triflusal or aspirin [11].
• CONCLUSIONS: This study suggests that triflusal neuroprotection is associated with a decrease of iNOS and other inflammatory mediators and therefore may constitute a good therapeutic agent in pathological situations in which regulation of inflammatory genes constitutes a relevant step in the outcome of the neurodegenerative event [21].
• However, only triflusal and aspirin inhibited purified COX-2 enzyme [20].
• 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-kappaB control are up-regulated [20].
• Plasma P-selectin and vWF were reduced by triflusal but not by aspirin [11].

Analytical, diagnostic and therapeutic context of Triflusal

• Electrophoretic mobility shift assay revealed an increase in the NF-kappaB binding activity in cardiac nuclear extracts of banded rats that was prevented by triflusal treatment [2].
• After administration of triflusal, we observed a reduction in microalbuminuria (59 +/- 25 vs. 33 +/- 22 micrograms/min, P less than 0.01), an increase in RPF (648 +/- 119 vs. 722 +/- 134 ml.min-1 x 1.73 m-2, P less than 0.01), and a reduction in filtration fraction (0.24 +/- 0.04 vs. 0.20 +/- 0.03, P less than 0.01) [22].
• One week old Long-Evans black hooded rat pups received three oral administrations of triflusal (30 mg/kg) and were sacrificed at 9 days of age [14].
• The biological effects of a new antiplatelet agent, triflusal, were evaluated in patients with cardiac valvular prostheses [17].
• RESULTS: After treatment with triflusal, there was an increase in NO production by neutrophils and an increase in endothelial nitric oxide synthase (eNOS) protein expression in neutrophils [13].

References