Effect of gliclazide on prostaglandin and thromboxane synthesis in guinea-pig platelets

Abstract

The inhibitory effect of gliclazide, a hypoglycemic sulfonylurea, on prostaglandin and thromboxane synthesis in guinea-pig platelets was studied. Gliclazide inhibited the thrombin-induced release of radioactive arachidonic acid from [ 14C] arachidonate-labeled platelets, and the concentration of 50% inhibition (IC 50) was 680 μg/ml. Gliclazide also inhibited in vitro the platelet malondialdehyde (MDA) formation induced by collagen but not by arachidonic acid, and IC 50 was 333 μg/ml. Gliclazide did not block the conversion of [ 14C] arachidonic acid to radioactive thromboxane A 2 (measured as a stable form, thromboxane B 2) in platelets. In ex vivo experiments, the platelet MDA formation induced by collagen but not by arachidonic acid was significantly inhibited by a single administration of gliclazide at 300 mg/kg, and this inhibition was enhanced by the repeated administrations for 7 days: namely, the significant inhibition was observed at 30 mg/kg/day. Thus gliclazide seems to inhibit in vitro and ex vivo arachidonate release from platelet phospholipids.