Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D04166 (FeCl3)
 1,389 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Further to characterize the processes involved in the FeCl3-induced thrombosis model, we determined the effect of aspirin, heparin, hirudin, trans-4-(aminomethyl) cyclohexane carboxylic acid (AMCHA), thrombocytopenia, and flow modifications on time to occlusion (TTO) and thrombus weight (TW) in the rat carotid artery. Aspirin, from 3 to 100 mg/kg, showed no dose-response relation for either TTO or TW and did not significantly affect ex vivo platelet aggregation. Heparin, at doses that significantly increased the activated partial thromboplastin time (APTT), dose-dependently increased the TTO of animals that showed an occlusion during the monitoring period and also reduced the TW. Hirudin required constant infusion to prevent occlusion and reduce the TW, when the APTT was also significantly increased. AMCHA did not affect the TW but reduced the TTO. Animals made thrombocytopenic by the use of antiplatelet serum did not occlude during the monitoring period, and the TW was significantly reduced. Changes in flow showed that the TTO was not affected, but the TW showed an inverse correlation with average flow. The results obtained for platelet depletion and flow modifications expand on previous findings with this model and support the physiological relevance of the model.
J Cardiovasc Pharmacol 1999 May
PMID:Demonstration of flow and platelet dependency in a ferric chloride-induced model of thrombosis. 1022 58

We examined the influence of dietary stable fish oil on aortic thrombosis, platelet aggregation, and superoxide dismutase (SOD) activity in a rat model. Twenty-nine Sprague-Dawley rats were fed regular chow supplemented with stable fish oil preparation (for 1 or 3 weeks), and 37 rats fed regular chow served as controls. The abdominal cavity was opened, and the abdominal aorta isolated. Whatman paper impregnated with 35% FeCl3 was wrapped around the surface of the aorta, and aortic flow was continuously recorded. In control rats, an occlusive platelet-fibrin-rich thrombus was formed in 21 +/- 3 min. Dietary fish oil in a time-dependent fashion delayed time to thrombus formation (24 +/- 2 min in rats fed fish oil for 1 week and 31 +/- 2 min in rats fed fish oil for 3 weeks), inhibited platelet aggregation (21 +/- 5% vs. 45 +/- 6%; p < 0.01) and increased SOD activity (p < 0.01). We conclude that dietary supplementation with stable fish oil delays formation of arterial thrombus, probably by reducing platelet aggregation and oxidative stress-associated arterial injury.
J Cardiovasc Pharmacol 2000 Mar
PMID:Effect of stable fish oil on arterial thrombogenesis, platelet aggregation, and superoxide dismutase activity. 1071 Jan 38

Statins (3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) have been shown to reduce clinical events in excess of what can be explained by altering lipid profile. Statins have been shown to possess modest antioxidant and antiplatelet aggregatory effect. We postulated that statins may accordingly inhibit arterial thrombus formation. To assess the antithrombotic effects of atorvastatin, a commonly used statin, in response to an oxidant stimulus, we fed Sprague-Dawley rats either regular chow, or chow mixed with atorvastatin (1.25 mg/kg) for 10 days (n = 16 in each group). Eight rats in each group were also given oxidized low-density lipoprotein intravenously prior to the induction of thrombus. An occlusive thrombus was created in the abdominal aorta by application of Whatman paper soaked in 35% FeCl3. The time to occlusive thrombus formation was not altered by administration of oxidized low-density lipoprotein in the rats fed regular chow or chow mixed with atorvastatin. However, time to thrombosis was increased in the group given chow mixed with atorvastatin (26 +/- 4 minutes vs. 20 +/- 5 minutes, P < 0.02). To determine the mechanism of atorvastatin's antithrombotic effect, we measured the expression of endothelial constitutive nitric oxide synthase (cNOS) in rat aortas by Western analysis. The cNOS protein expression was enhanced 75% in rats fed chow with atorvastatin (P < 0.01 vs. rats fed regular chow). Plasma levels of total cholesterol and low-density lipoprotein-cholesterol were similar in all groups. This study shows that atorvastatin delays thrombus formation in arterial channels exposed to oxidant stress. This effect of atorvastatin appears to be related to increased expression of cNOS, which is known to inhibit platelet aggregation and induce vasodilatation. The effects of atorvastatin are independent of its effects on plasma cholesterol levels.
J Cardiovasc Pharmacol Ther 2002 Oct
PMID:Anti-thrombotic effects of atorvastatin--an effect unrelated to lipid lowering. 1249 Sep 71

PD-198961, 3-(4-5-[(2R,6S)-2,6-dimethyltetrahydro-1(2H)-pyridinyl]pentyl-3-oxo-3,4-dihydro-2-quinoxalinyl)-4-hydroxybenzenecarboximidamide, is a novel, synthetic factor Xa inhibitor with a Ki of 2.7 nM against human factor Xa. The aim of the present study was to evaluate the pharmacokinetic profile and antithrombotic efficacy of PD-198961 in rabbits. When tested in vitro, PD-198961 doubled prothrombin time (PT) and activated partial thromboplastin time (aPTT) at concentrations of 0.13 and 0.32 microM in human plasma, 0.2 and 0.09 microM in rabbit plasma, 0.3 and 0.4 microM in dog plasma, respectively. Intravenous administration of PD-198961 at 1 mg/kg over 30 minutes resulted in a maximal prolongation in PT and aPTT of 4.9 +/- 0.4 and 4.1 +/- 0.9-fold of baseline, respectively. The peak plasma concentration of PD-198961 was 977 +/- 96 ng/ml. The anticoagulant effect of PD-198961 was readily reversible; coagulation parameters and plasma concentration returned to near baseline 15 minutes after cessation of infusion. There was a good correlation between PT prolongation and plasma concentration of PD-198961 (r = 0.93). In an FeCl3-induced model of arterial thrombosis in rabbits, the antithrombotic effects of PD-198961 were compared with that of LB-30057, a direct thrombin inhibitor, and enoxaparin, a low molecular weight heparin (LMWH). PD-198961 dose dependently increased the time to occlusion (TTO), reduced thrombus weight (TW), and decreased the incidence of occlusion. When administered at 3.0 microg/kg/min IV, PD-198961 prolonged TTO from 28 +/- 5 minutes (control) to 120 +/- 0 minutes (P < 0.001) and reduced TW from 9.9 +/- 1.5 mg (control) to 2.8 +/- 0.9 mg (P < 0.01). PD-198961 also dose dependently inhibited ex vivo plasma FXa activity. At the highest dose tested, PD-198961 increased aPTT to 1.4 +/- 0.1-fold of baseline (compared with 1.5 +/- 0.1 and 2.8 +/- 0.3-fold of baseline for LB-30057 [CI-1028] and enoxaparin, respectively), and had modest effects on bleeding time (< or = 2-fold). These results indicate that PD-198961 is a potent FXa inhibitor and an effective antithrombotic agent at doses that produce only modest changes in normal hemostasis.
J Cardiovasc Pharmacol 2004 Oct
PMID:In vitro and in vivo antithrombotic activity of PD-198961, a novel synthetic factor Xa inhibitor. 1545 59

Acute coronary syndromes are caused by platelet-mediated thrombosis following rupture of a plaque. HMG-CoA reductase inhibitors (statins) reduce the incidence of events early after acute coronary syndromes, which are independent of its cholesterol-lowering effect. Accordingly, we investigated whether statins inhibit platelet-mediated arterial thrombus formation in vivo and, if so, the underlying mechanisms. Rats were divided into 4 groups. Group 1 was treated with the vehicle, whereas groups 2, 3, and 4 were treated with cerivastatin for 7 days (1, 2, and 5 mg/kg i.p., respectively). Cerivatatin did not change serum cholesterol levels. Carotid arterial thrombosis was created by perivascular FeCl3 delivery. Cerivastatin significantly prolonged the time to thrombotic occlusion of carotid artery. Cerivastatin significantly dose-dependently inhibited both ex vivo platelet P-selectin expression, a marker of platelet activation, and platelet aggregation. Cerivastatin significantly augmented platelet-derived nitric oxide (NO) release, and up-regulated platelet and endothelial nitric oxide synthase (NOS) mRNA expressions. N-nitro-L-arginine methylester abolished the effects of cerivastatin. This study demonstrates that in vivo administration of statin protects against platelet-mediated arterial thrombosis, possibly by augmenting platelet- and endothelium-derived NO releases via up-regulation of platelet and endothelial NOS.
J Cardiovasc Pharmacol 2005 Apr
PMID:HMG-CoA reductase inhibitor protects against in vivo arterial thrombosis by augmenting platelet-derived nitric oxide release in rats. 1577 28