6-ketoprostaglandin-f1-alpha and Venous-Thrombosis

We investigated the production of prostacyclin and thromboxane in pregnant women with a previous venous thromboembolic event before, during and after the use of unfractionated heparin and low molecular weight heparin (dalteparin). Twenty women were studied before starting heparin prophylaxis (before 20 weeks of gestation), during heparin prophylaxis (at 30 weeks of gestation) and after heparin prophylaxis (16 weeks after delivery). Ten pregnant women with no history of thromboembolism were studied as the control group. Urinary output of the stable metabolite of prostacyclin (2,3-dinor-6-keto-PGF1alpha) and that of thromboxane A2 (2,3-dinor-TxB2), as well as a number of markers of thrombophilia were measured and expressed as mean (+/-SEM). Women with a history of thromboembolism were characterized by normal prostacyclin production but elevated thromboxane production (44.0 +/- 4.1 versus 19.0 +/- 3.6 ng/mmol creatinine, P < 0.001) at 12 weeks of pregnancy. Heparin prophylaxis (regardless of the type) had abolished elevated thromboxane concentrations at 30 weeks of gestation. Four months after delivery, thromboxane dominance had returned (25.2 +/- 3.5 versus 13.6 +/- 2.1 ng/mmol creatinine, P < 0.01). The presence of hereditary thrombophilia (9/20) was not associated with any changes in prostanoid concentrations. Thus, women with a history of venous thromboembolic events have thromboxane dominance during and after pregnancy, but this dominance can be eliminated through the use of heparins.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Analysis of Variance; Anticoagulants; Body Mass Index; Case-Control Studies; Dalteparin; Factor V; Female; Heparin; Heparin, Low-Molecular-Weight; Humans; Postpartum Period; Pregnancy; Pregnancy Complications, Hematologic; Pregnancy Outcome; Statistics, Nonparametric; Thromboxane B2; Thromboxanes; Venous Thrombosis

The present study was designed to explore the regulatory mechanisms and influences of cotinine on deep vein thrombosis (DVT) in rats via the toll-like receptor 4/nuclear factor κ binding (TLR-4/NF-κB) pathway.. In this experimental study, 30 SD rats were randomly assigned to control group, sham operation group, model group, cotinine (10 μg/kg) group, and model + cotinine (10 μg/kg) group. The thromboxane B2 (TXB2), 6-keto-PGF1α, plasminogen activator inhibitor (PAI), tissue plasminogen activator (t-PA), TLR4, NF-κB, and p65 mRNA and protein expression and tissue changes were analyzed by ELISA, Hematoxylin-Eosin (HE) staining, RT-PCR, and Western blot.. There was no significant difference between the control and sham operation groups (P>0.05). The model and cotinine groups showed significantly higher mRNA and protein levels of TXB2, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), PAI, TLR-4, and NF-κB, and significantly lower levels of 6-keto-PGF1α and t-PA than the control and sham operation groups (P<0.05), and the model + cotinine group showed significantly higher mRNA and protein levels of TXB2, IL-6 and TNF-α, PAI, TLR-4, and NF-κB and significantly lower levels of 6-keto-PGF1α and t-PA than the model group (P<0.05).. Cotinine can aggravate thrombus and inflammation in rats with DVT, and the mechanism may be associated with the activation of the TLR-4/NF-κB inflammatory signaling pathway.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Anti-Inflammatory Agents; Cotinine; Disease Models, Animal; Fibrinolytic Agents; Male; NF-kappa B; Rats, Sprague-Dawley; Signal Transduction; Thromboxane B2; Toll-Like Receptor 4; Venous Thrombosis

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

Danshensu, a type of dihydroxyphenyl lactic acid, is one of the most abundant active phenolic acids in the dried root of Salvia miltiorrhizae (Lamiaceae)--widely used traditional Chinese medicine. The effects of danshensu on platelet aggregation and thrombus formation in rats were examined using various methods. It was found that danshensu significantly reduced thrombus weight in 2 experimental thrombosis models; dose-dependent inhibition of adenosine diphosphate (ADP) and arachidonic acid (AA)-induced platelet aggregation occurred in normal and blood stasis-induced rats; Danshensu also significantly mitigated blood viscosity, plasma viscosity and hematocrit levels. Moreover, danshensu significantly inhibited venous thrombosis-induced expression of cyclooxygenases-2 (COX-2) rather than cyclooxygenases-1(COX-1) in the venous walls, down regulated thromboxane B2 (TXB2) and up regulated 6-keto prostaglandin F1α (6-keto-PGF1α), normalizing the TXB2/6-keto-PGF1α ratio. In addition, danshensu did not induce gastric lesions and even had protective effects on aspirin-induced ulcer formation at doses as high as 60 mg/kg. These findings suggest that the antithrombotic and antiplatelet aggregation effects of danshensu are attributed to its highly selective inhibition of COX-2 and ability to normalize the thromboxane A2(TXA2)/prostacyclin(PGI2) balance. These findings suggest that danshensu have great prospects in antithrombotic and antiplatelet therapy.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Cyclooxygenase 1; Cyclooxygenase 2; Disease Models, Animal; Lactates; Platelet Aggregation; Rats; Thromboxane A2; Thromboxane B2; Venous Thrombosis

To investigate the effects of Qushuanling Capsule ( QSLC) on thrombus formation and platelet aggregation in rats.. Arteriovenous bypass, venous thrombosis, and middle cerebral artery thrombosis models were used in rats to investigate the anti-thrombotic effects of QSLC, a compound of nine Chinese herbs. The platelet aggregation induced by adenosine diphosphate (ADP), thrombin or arachidonic acid (AA), as well as the contents of thromboxane B(2) (TXB(2)) and 6-keto-prostaglandin F1α (6-keto-PGF1α) in rat plasma and aortic walls, were determined to investigate the possible mechanisms of the anti-thrombotic effects of QSLC.. After oral administration with QSLC for 7 days, arteriovenous bypass thrombosis was obviously suppressed compared with the model group, venous thrombosis was also obviously suppressed, rat behaviors were obviously improved, and brain infarct size as well as water content were also reduced. The platelet aggregation induced by ADP or thrombin was inhibited by QSLC, but the drug had no effect on AA-induced platelet aggregation and content of TXB(2) and 6-keto-PGF1α in plasma and the aortic wall.. These results suggest that QSLC can be used in the prevention and treatment of thrombotic diseases, and that its mechanism of action may be related to inhibition of platelet aggregation.

Topics: 6-Ketoprostaglandin F1 alpha; Adenosine Diphosphate; Animals; Aorta; Cerebral Infarction; Drugs, Chinese Herbal; Male; Middle Cerebral Artery; Platelet Aggregation; Rats; Rats, Sprague-Dawley; Thrombosis; Thromboxane B2; Venous Thrombosis

Interleukin-18 (IL-18) is an important proinflammatory cytokine. However, little is known about the roles of IL-18 in the process of venous thrombosis. This study aimed to investigate the roles of IL-18 during deep vein thrombosis (DVT).. Fifty rats were randomly divided into 0 (control group), 12, 24, 36 and 48 h groups (10 rats in each group) by observation time. The inferior vena cava (IVC) was ligated to establish the DVT model. Serum samples were extracted to determine the levels of IL-18, tumor necrosis factor-alpha (TNF-α), thromboxane B2 (TXB2) and 6-keto-prostaglandin Fl alpha (6-keto-PG Flα) by enzyme-linked immunosorbent assay (ELISA). The weight and length of IVC was also measured.. The DVT model was successfully established by ligating IVC. The injury of vein endothelium was observed in the model groups. IL-18, TNF-α, TXB2, TXB2/6-keto-PG Flα levels and thrombus weight were significantly increased in the model groups as compared with the control group, and peaked at 24 h after IVC ligation. 6-keto-PG F1α slightly decreased in the model groups comparing with the control group. IL-18 was positively correlated with TNF-α, TXB2, TXB2/6-keto-PG Flα ratio and thrombus weight. However, IL-18 was negatively correlated with 6-keto-PG Flα. There was a positive correlation between TXB2/6-keto-PG Flα ratio and thrombus weight.. Serum IL-18 level increased in the process of DVT, which might impair venous endothelial cells and result in venous thrombosis. IL-18 might be a new potential therapeutic target of DVT prevention.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Inflammation Mediators; Interleukin-18; Ligation; Male; Rats; Rats, Sprague-Dawley; Thromboxane B2; Time Factors; Tumor Necrosis Factor-alpha; Up-Regulation; Vena Cava, Inferior; Venous Thrombosis

D-003 is a natural mixture of higher primary saturated aliphatic acids purified from sugar cane wax, whose main component is octacosanoic acid followed by triacontanoic, dotriacontanoic, and tetratriacontanoic acids. D-003 inhibits platelet aggregation and arterial thrombosis experimentally induced in a dose-dependent fashion. This study was undertaken to investigate the effects of D-003 (25 and 200 mg/kg) in experimental models of venous thrombosis and on plasma levels of two metabolites from arachidonic acid (AA) : thromboxane A(2) (TxA(2)) and prostacyclin (PgI(2)). D-003 orally administered as single doses of 200 mg/kg, but not at 25 mg/kg, significantly increased plasma levels of 6 keto PgF1alpha levels, a stable metabolite of PgI(2) in PPP obtained from collagen-stimulated blood (4 microg/ml) compared with control group. Nevertheless, levels of 6 keto PgF1alpha levels determined after 10 days of oral treatment with both doses of D-003 were significantly larger than those of the controls. Likewise, single and repeated oral doses of D-003 (25 and 200 g/kg) significantly reduced the TxB(2) and MDA plasma levels obtained from whole blood stimulated by collagen. Hence, TxB(2)/6 keto PgF1alpha ratio significantly decreased in animals treated with D-003. Single and repeated oral doses of D-003 (25 and 200 mg/kg) significantly reduced the weight of venous thrombus experimentally induced in rats. D-003 at single doses (400 mg/kg but not 200 mg/kg) significantly protected from death induced by endovenous infusion of collagen plus epinephrine in mice. The present results support that these effects of D-003 on AA metabolites could explain, at least partially, its antiplatelet and antithrombotic effects.

Topics: 6-Ketoprostaglandin F1 alpha; Administration, Oral; Animals; Arachidonic Acid; Blood Platelets; Collagen; Epinephrine; Fatty Acids; Fibrinolytic Agents; Male; Platelet Aggregation; Rats; Rats, Sprague-Dawley; Saccharum; Statistics, Nonparametric; Survival Analysis; Thromboxane B2; Venous Thrombosis; Waxes