Reduction in lipopolysaccharide-induced thrombocytopenia by triflavin in arat model of septicemia

Background-Thrombscytopenia frequently occurs early in the course of Grant- negative bacterial infections. Triflavin, an Arg-Gly-Asp-containing disinte grin, has been suggested to interfere with the interaction of fibrinogen wi th the glycoprotein IIb/IIIa complex. The present study was undertaken to d etermine whether triflavin could prevent thrombocytopenia in lipopolysaccha ride (LPS)-treated rats. Methods and Results-In this study, Cr-51-labeled platelets were used to ass ess blood and tissue platelet accumulation after LPS challenge, The adminis tration of LPS (4 mg/kg TV bolus) for 4 hours induced a reduction in mdiolo beled platelets in blood and an obvious accumulation of platelets in liver. Triflavin (500 mu g/kg) but not GRGDS (20 mg/kg) significantly prevented t he alteration of radiolabeled platelet distribution in blood and liver when induced by LPS. Furthermore, triflavin but not GRGDS markedly suppressed t he elevation in plasma thromboxane B-2 concentration within the 4-hour peri od of LPS administration. In LPS-treated rats, the 5-hydroxytryptamine leve l was lower in the blood and higher in the liver compared with levels in no rmal saline-treated rats, Pretreatment with triflavin (500 mu g/kg) signifi cantly reversed the 5-hydroxytryptamine concentration in blood and liver of LPS-treated mts, In histological examinations and platelet adhesion assay, triflavin markedly inhibited the adhesion of platelets to subondothelial m atrixes in vivo and in vitro. Conclusions The results indicate that triflavin effectively prevents thromb ocytopenia, possibly through the following 2 mechanisms: (1) Triflavin mark edly inhibits platelet aggregation, resulting in decreased thromboxane A(2) formation. (2) It inhibits the adhesion of platelets to subendothelial mat rixes, thereby leading to a reversal in the distribution of platelets in bl ood and liver in LPS-treated rats.