In vivo anticoagulant effect of ethyl pyruvate in endotoxemic rats

• Published in: Thrombosis research 2011-06, Vol.127 (6), p.582-588
• Main Authors: Kung, Ching-Wen, Lee, Yen-Mei, Yen, Mao-Hsiung
• Format: Article
• Language: English
• Subjects: Animals; Anticoagulants - pharmacology; Biological and medical sciences; Blood and lymphatic vessels; Blood Coagulation - drug effects; Blood. Blood coagulation. Reticuloendothelial system; Cardiology. Vascular system; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Disseminated intravascular coagulation; Disseminated Intravascular Coagulation - blood; Disseminated Intravascular Coagulation - drug therapy; Dose-Response Relationship, Drug; Endotoxemia - blood; Ethyl pyruvate; Hematology, Oncology and Palliative Medicine; Humans; Male; Medical sciences; Pharmacology. Drug treatments; Plasminogen activator inhibitor-1; Pyruvates - pharmacology; Rats; Rats, Inbred WKY; Sepsis; Thrombin-antithrombin complex; Tissue factor
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/j.thromres.2011.01.017

Abstract Introduction Disseminated intravascular coagulation (DIC), a disorder of the blood coagulation function, is a common complication of severe sepsis. Ethyl pyruvate (EP), a derivative of pyruvate, is known for its anti-inflammatory and antioxidant properties. Recently, EP showed anticoagulant effects in vitro . Therefore, the aim of study is to investigate the in vivo anticoagulant effect of EP on a severe DIC model induced by lipopolysaccharide (LPS) in anesthetized Wistar rats. Materials and Methods The animals were intravenously infused with LPS (30 mg/kg) over a period of 4 h. One hour after LPS initiation, rats were treated with EP in three dosages (20, 40 and 60 mg/kg/4 h, i.v.). Results The intermediate and high doses of EP (40 and 60 mg/kg) prevented circulatory failure, improved renal and hepatic function, and reduced the plasma levels of TNF-α and IL-6 after LPS administration. All used doses of EP significantly prevented prothrombin time prolongation, and reduced mRNA expression of tissue factor in lung tissue induced by LPS. The two higher doses of EP attenuated plasma concentrations of thrombin-antithrombin complex. The high dose of EP (60 mg/kg) significantly preserved platelet counts, and improved survival rate. However, EP did not reduce the elevation of plasma plasminogen activator inhibitor-1 during endotoxemia. Conclusion EP demonstrates the in vivo anticoagulant effect and improved organ functions in a severe DIC model in rats, which is likely associated with the inhibitory effect on tissue factor mRNA expression and cytokines release. Its effectiveness in preventing DIC is not mediated by increase in fibrinolysis.