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(Circulation. 1999;99:3056-3062.)
© 1999 American Heart Association, Inc.

Basic Science Reports

Reduction in Lipopolysaccharide-Induced Thrombocytopenia by Triflavin in a Rat Model of Septicemia

Joen-Rong Sheu, PhD; Wei-Chung Hung, MS; Ching-Hsiang Wu, PhD; Ming-Chieh Ma, MS; Ya-Chen Kan, MS; Chien-Huang Lin, PhD; Ming-Shyan Lin, MD, PhD; Hsiung-Ning Luk, MD, PhD; Mao-Hsiung Yen, PhD

From the Graduate Institute of Medical Sciences (J.-R.S., M.-C.M., Y.-C.K., C.-H.L.), the Department of Anatomy (C.-H.W.), Taipei Medical College; Institute of Life Sciences (W.-C.H.), Institute of Medical Sciences (M.-S.L.), the Department of Pharmacology (H.-N.L., M.-H.Y.), National Defense Medical Center, Taipei, Taiwan.

Correspondence to Dr Joen-Rong Sheu, Graduate Institute of Medical Sciences, Taipei Medical College, No. 250, Wu-Shing St, Taipei 110, Taiwan. E-mail sheujr{at}tmc.edu.tw

Background—Thrombocytopenia frequently occurs early in the course of Gram-negative bacterial infections. Triflavin, an Arg-Gly-Asp–containing disintegrin, has been suggested to interfere with the interaction of fibrinogen with the glycoprotein IIb/IIIa complex. The present study was undertaken to determine whether triflavin could prevent thrombocytopenia in lipopolysaccharide (LPS)-treated rats.

Methods and Results—In this study, ⁵¹Cr-labeled platelets were used to assess blood and tissue platelet accumulation after LPS challenge. The administration of LPS (4 mg/kg IV bolus) for 4 hours induced a reduction in radiolabeled platelets in blood and an obvious accumulation of platelets in liver. Triflavin (500 µg/kg) but not GRGDS (20 mg/kg) significantly prevented the alteration of radiolabeled platelet distribution in blood and liver when induced by LPS. Furthermore, triflavin but not GRGDS markedly suppressed the elevation in plasma thromboxane B₂ concentration within the 4-hour period of LPS administration. In LPS-treated rats, the 5-hydroxytryptamine level was lower in the blood and higher in the liver compared with levels in normal saline–treated rats. Pretreatment with triflavin (500 µg/kg) significantly reversed the 5-hydroxytryptamine concentration in blood and liver of LPS-treated rats. In histological examinations and platelet adhesion assay, triflavin markedly inhibited the adhesion of platelets to subendothelial matrixes in vivo and in vitro.

Conclusions—The results indicate that triflavin effectively prevents thrombocytopenia, possibly through the following 2 mechanisms: (1) Triflavin markedly inhibits platelet aggregation, resulting in decreased thromboxane A₂ formation. (2) It inhibits the adhesion of platelets to subendothelial matrixes, thereby leading to a reversal in the distribution of platelets in blood and liver in LPS-treated rats.

Key Words: platelets • platelet aggregation inhibitors • peptides • thromboxane

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