thromboxane-b2 and ferric-chloride

Zhi-Xiong Capsules (ZXC) involving Hirudo, Ligusticum chuanxiong, Salvia miltiorrhiza, Leonurus artemisia, and Pueraria lobata, is an empirical prescription used in Chinese clinics applied for treating cerebral arteriosclerosis and blood-stasis in clinic. However, the mechanism of its antithrombotic activity has not been investigated until now. The present study was designed to investigate its antithrombotic effects, the mechanism of ZXC on anti-thrombus action and to identify the main chemical composition of ZXC using HPLC-DAD-ESI-IT-TOF-MS. Two animal models were used to evaluate the antithrombotic effect of ZXC, the arterial thrombosis model and a venous thrombosis model. ZXC prolonged the plasma recalcification time (PRT), the activated partial thromboplastin time (APTT), the thrombin time (TT) and the prothrombin time (PT) and clearly reduced the content of fibrinogen (FIB) obviously in the arterial thrombosis model. Furthermore, it markedly suppressed the level of TXB

Topics: Acute Disease; Animals; Anticoagulants; Antithrombins; Aspirin; Blood Coagulation; Capsules; Carotid Arteries; Chlorides; Disease Models, Animal; Drug Evaluation, Preclinical; Drugs, Chinese Herbal; Ferric Compounds; Fibrinolysis; Heparin; Lung; Mice; Platelet Activation; Platelet Aggregation; Prostaglandins F; Pulmonary Embolism; Rabbits; Rats, Sprague-Dawley; Thrombolytic Therapy; Thrombosis; Thromboxane B2

Cydonia oblonga Miller (COM) is traditionally used in Uyghur medicine for the prevention of cardiovascular disease. The present study is designed to explore the effects of COM extracts on models and markers of thrombosis and related biomarkers.. 20, 40, 80 mg/kg/day COM aqueous extracts and 5mg/kg/day aspirin, orally for 14 days were compared to untreated controls in mice on bleeding and clotting times, using the tail cutting and glass slide methods and for death rates in collagen-epinephrine pulmonary thrombosis, thrombolysis in vitro and euglobulin lysis time (ELT). In rats, common carotid artery FeCl3-induced thrombus and inferior vena cava thrombosis occlusion time, plasma concentrations of thromboxane B2 (TXB2) and 6-keto-prostaglandine F1α (6-keto-PGF1α) were measured.. Compared to controls, COM extracts dose-dependently prolonged bleeding by 2.17, 2.78 and 3.63 times, vs. aspirin 2.58, and the clotting time by 1.44, 2.47 and 2.48 times, vs. aspirin 1.91. COM reduced pulmonary embolus mortality by 27, 40 and 53%, vs. 47% for aspirin. COM dose-dependently increased thrombolysis by 45, 55 and 63%, vs. 56% for aspirin, and shortened ELT to 71, 61 and 43%, vs. 43% for aspirin. In rats, venous occlusion time was prolonged. Arterial and venous thrombus weights were dose-dependently reduced in COM groups. TXB2 decreased and 6-keto-PGF1α increased with COM and aspirin, with an association between 6-keto-PGF1α/TXB2 and arterial or venous thrombus weight for all products, and for occlusion time with COM but not for aspirin.. We confirm the experimental effects of COM on hemostasis and thrombosis. Further exploration of putative clinical effects appear justified.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Blood Coagulation; Cardiovascular Agents; Carotid Artery Thrombosis; Chlorides; Collagen; Epinephrine; Ferric Compounds; Fibrinolysis; Hemostasis; Male; Mice, Inbred ICR; Phytotherapy; Plant Extracts; Plant Leaves; Pulmonary Embolism; Rats, Wistar; Rosaceae; Thromboxane B2; Vena Cava, Inferior; Venous Thrombosis

Selective cyclooxygenase-2 (COX-2) inhibitors (coxibs) increase the incidence of cardiovascular and cerebrovascular events. Complete disruption of the murine gene encoding COX-2 (Ptgs2) leads to renal developmental problems, as well as female reproductive anomalies and patent ductus arteriosus of variable penetrance in newborns, thus rendering this genetic approach difficult to compare with coxib administration. Here, we created hypomorphic Ptgs2 (COX-2(Neo/Neo)) mice in which COX-2 expression is suppressed to an extent similar to that achieved with coxibs, but not eliminated, in an attempt to circumvent these difficulties. In LPS-challenged macrophages and cytokine-stimulated endothelial cells obtained from COX-2(Neo/Neo) mice, COX-2 expression was reduced 70-90%, and these mice developed a mild renal phenotype compared with COX-2 mice possessing an active site mutation (COX-2(Y385F/Y385F)), with minimal signs of renal dysfunction as measured by FITC-inulin clearance and blood urea nitrogen. These COX-2 knockdown mice displayed an increased propensity for thrombogenesis compared with their wild-type (COX-2(+/+)) littermates observed by intravital microscopy in cremaster muscle arterioles upon ferric chloride challenge. Measurement of urinary prostanoid metabolites indicated that COX-2(Neo/Neo) mice produced 50% less prostacyclin but similar levels of PGE(2) and thromboxane compared with COX-2(+/+) mice in the absence of any blood pressure and ex vivo platelet aggregation abnormalities. COX-2(Neo/Neo) mice, therefore, provide a genetic surrogate of coxib therapy with disrupted prostacyclin biosynthesis that predisposes to induced arterial thrombosis.

Topics: Animals; Blood Pressure; Blood Urea Nitrogen; Cardiovascular System; Cells, Cultured; Chlorides; Cyclooxygenase 1; Cyclooxygenase 2; Cytokines; Dinoprostone; Disease Models, Animal; Endothelial Cells; Epoprostenol; Ferric Compounds; Glomerular Filtration Rate; Heart Rate; Kidney; Macrophages, Peritoneal; Membrane Proteins; Mice; Mice, Knockout; Microscopy, Video; Thrombosis; Thromboxane B2; Time Factors

Diclofenac, like selective cyclooxygenase-2 inhibitors, which alter vascular levels of platelet active prostaglandins, has been reported to increase rates of acute myocardial infarction.. The study was performed to investigate, in an animal model of arterial thrombosis in vivo, whether diclofenac differentially influences platelet activation and thrombosis in vessels under non-stimulated conditions or during acute systemic inflammation, such as induced by tumor necrosis factor-alpha (TNF-alpha).. Platelet-vessel wall interaction (PVWI), firm platelet adhesion and arterial thrombosis following vessel injury were analyzed by intravital microscopy in arterioles of hamsters in the dorsal skinfold chamber model. Prostacyclin [prostaglandin I(2) (PGI(2))] and thromboxane A(2) (TxA(2)) metabolites were measured. In vitro, endothelial adhesion molecule expression in cultured human microvascular endothelial cells was analyzed.. Under non-stimulated conditions, diclofenac (1 mg kg(-1)) enhanced PVWI, which was not mediated by increased adhesion molecule expression, but by decreased systemic PGI(2) levels. Following ferric chloride-induced endothelial injury, diclofenac accelerated thrombotic vessel occlusion time, an effect that was reversed by the stable PGI(2) analog iloprost. TNF-alpha, through induction of endothelial adhesion molecule expression, also enhanced PVWI, firm adhesion, and arterial thrombosis, but simultaneous treatment with TNF-alpha and diclofenac did not have an additive effect.. By decreasing levels of PGI(2) without, at the same time, altering prothrombotic TxA(2) levels, diclofenac can exert prothrombotic effects. However, this is not the case when an inflammatory situation is created by TNF-alpha treatment. These data may explain the enhanced risk of acute myocardial infarction observed in patients taking diclofenac.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arterioles; Cells, Cultured; Chlorides; Cricetinae; Cyclooxygenase Inhibitors; Diclofenac; Endothelium, Vascular; Ferric Compounds; Humans; Mesocricetus; Mice; Mice, Inbred C57BL; Microscopy, Fluorescence; Platelet Activation; Platelet Adhesiveness; Skin Window Technique; Thromboplastin; Thrombosis; Thromboxane B2; Tumor Necrosis Factor-alpha