Inhibition of thromboxane biosynthesis by triflusal in type 2 diabetes mellitus.
Triflusal is an antiplatelet drug related to aspirin, with different pharmacological properties and a lower haemorrhagic risk. We aimed at comparing their effects on platelet and endothelial activation in type 2 diabetes mellitus (T2DM). In a randomized, double-blind, parallel group study, we compared the effects of three daily regimens (300, 600, and 900 mg) of triflusal, and aspirin (100mg/day) on urinary 11-dehydro-thromboxane (TX)B(2), index of in vivo platelet activation, ex vivo platelet function using the analyzer PFA-100, plasma von Willebrand factor (vWF), P-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and serum nitrite and nitrate (NO(2)(-)+NO(3)(-)) in 60 T2DM patients. Triflusal induced a dose-dependent reduction in 11-dehydro-TXB(2) and a prolongation of closure time in the presence of collagen plus epinephrine (Coll/Epi-CT). The effects of the highest triflusal dose were not different from those of aspirin. 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. Plasma P-selectin and vWF were reduced by triflusal but not by aspirin. 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.
Falco
A
A
Fondazione Università "G. d'Annunzio", Center of Excellence on Aging and Department of Medicine and Aging, University of Chieti, "G. d'Annunzio" School of Medicine, via Colle dell'Ara, 66013 Chieti, Italy.
Salvati
F
F
Vitacolonna
E
E
Avellone
G
G
Pinto
A
A
Di Febbo
C
C
Ballone
E
E
Di Nicola
M
M
Ciabattoni
G
G
Davì
G
G
D000328:Adult; D000368:Aged; D001241:Aspirin / Q000008:administration & dosage / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood / Q000187:drug effects; D015539:Platelet Activation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D011863:Radioimmunoassay; D012189:Retrospective Studies; D012459:Salicylates / Q000008:administration & dosage / Q000627:therapeutic use*; D013929:Thromboxane B2 / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000652:urine; D014841:von Willebrand Factor / Q000187:drug effects / Q000378:metabolism
D015415:Biomarkers; D019007:P-Selectin; D010975:Platelet Aggregation Inhibitors; D012459:Salicylates; D014841:von Willebrand Factor; C016167:triflusal; D013929:Thromboxane B2; C049235:11-dehydro-thromboxane B2; D001241:Aspirin