Jpn. J. Pharmacol. 76 (4), 397-404 (1998)

Effects of Dermatan Sulfate, a Heparin Cofactor II Mediated Thrombin Inhibitor, on the Endotoxin-Induced Disseminated Intravascular Coagulation Model in the Rat: Comparison With Low-Molecular Weight Heparin, Nafamostat Mesilate and Argathroban

Junichi Onaya, Mamoru Kyogashima, Atsuko Sunose, Satoshi Miyauchi, Syoji Mizuno and Katsuyuki Horie

Tokyo Research Institute, Seikagaku Corporation, 3-1253 Tateno, Higashiyamato, Tokyo 207-0021, Japan

Abstract: Effects of dermatan sulfate (DS) on the endotoxin-induced disseminated intravascular coagulation (DIC) rat model were compared with those of low-molecular weight heparin (LMWH), nafamostat mesilate (NM) and argathroban (AR). At doses of 5, 10 or 20 mg/kg/4 hr, DS significantly ameliorated the decrease of fibrinogen (Fbg), the increase of fibrin-fibrinogen degradation products (FDP) and except at the highest dose (20 mg/kg/4 hr), the prolongation of thrombin clotting time (TCT). It also decreased the glomerular fibrin deposits (%GFD) at doses of 10 or 20 mg/kg/4 hr. LMWH suppressed the decrease of Fbg and the increase of FDP at doses of 1.4 or 2.8 mg/kg/4 hr. Only the highest dose of LMWH suppressed the decrease of the platelet count (PL), the prolongation of prothrombin time, and improved the %GFD. AR suppressed the decrease of PL and improved the %GFD. At the dose required to improve the %GFD, DS (5, 10 mg/kg/4 hr) significantly suppressed the prolongation of TCT, which is related to the bleeding frequency, while LMWH and AR further increased the prolongation of the TCT. These results suggest that DS has potential as a therapeutic drug with a lower hemorrhagic risk as compared with LMWH and AR in the treatment of DIC.

Keywords: Endotoxin, Dermatan sulfate, Disseminated intravascular coagulation, Hemorrhagic tendency, Thrombin clotting time

Copyrightę The Japanese Pharmacological Society 1998

[Back to TOC]