Coagulation Activation by Lipopolysaccharides

An important problem of treating patients with endotoxemia is to find drugs to reduce the negative effects of endotoxin on the organism. We tested fucoidan (sulfated polysaccharide) from the brown alga Fucus evanescens as a potential drug in a mouse model of endotoxemia inducted by lipopolysaccharide (LPS). The survival time of mice injected with LPS increased under fucoidan treatment compared with the group of mice injected with LPS only. The preventive administration of fucoidan to mice with endotoxemia resulted in inhibition of increased levels of proinflammatory cytokines (TNFα and IL-6), as well as decreasing of the processes of hypercoagulability. The parenteral or per os administration of fucoidan resulted in decreasing the degree of microcirculatory disorders and secondary dystrophic-destructive changes in parenchymal organs of mice with endotoxemia. Taken together, these results demonstrate that fucoidan prevents endotoxin-induced damage in a mouse model of endotoxemia and increases the mice’s resistance to LPS.

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“…symptoms. Without adequate treatment, these symptoms steadily progress and become fatal [19,21,28,29]. …”

Section: Resultsmentioning

confidence: 99%

Fucoidan Extracted from Fucus evanescens Prevents Endotoxin-Induced Damage in a Mouse Model of Endotoxemia

et al. 2014

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“…The ultrasound energy seems to fold the latent proenzyme prekallikrein into the active enzyme kallikrein. The clinical consequence of this action of ultrasound on both main triggers (factor 12a and kallikrein) of intrinsic coagulation is that patients at risk for thrombosis, for example, patients with insufficiencies of hepatocytes [10], AT-3 [11], C1-ina [8,12], or fibrinolysis [13], or patients with increased circulating concentrations of intrinsic or extrinsic coagulation triggers [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] or with stasis of blood flow should be protected by low-molecular-weight-heparin [31][32][33][34][35][36][37] prior to the exposure of ultrasound, especially when using its prolonged exposure. Further folding of ultrasound-activated prekallikrein might inactivate the enzyme, as, for example, seen in ultrasound exposure for more than 3.5 min (23 8C).…”

Section: Resultsmentioning

confidence: 99%

Diagnostic ultrasound activates pure prekallikrein

Stief¹,

Klingmüller

2012

Blood Coagulation &Amp; Fibrinolysis

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Diagnostic ultrasound activates the contact phase of human coagulation. This has been seen in human blood or plasma or with purified factor 12. The present work aimed to quantify a possibly triggering action of ultrasound on purified prekallikrein, the second of the two main triggers of the intrinsic hemostasis cascade. Either 2.7 μg/ml human prekallikrein or for control 1 μg/ml kallikrein in 26% glycerol - 0.54% NaCl-10.6 mmol/l Na3 citrate pH 7.4, in emptied polypropylene coagulation monovettes (Sarstedt) were exposed to diagnostic ultrasound (Siemens Acouson Antares, 5 MHz, 0.6 TIB, 0.6 TIS) for 0-5 min at room temperature (RT). Fifty microliter samples were withdrawn in duplicate and placed into an U-wells high quality microtiter plate (Brand 781600). Then 10 μl 2 mmol/l chromogenic substrate HD-CHG-Ala-Arg-pNA in 0.45% NaCl were added, and the increase in absorbance with time (ΔA405 nm /t at 37°C) was determined by a microtiterplate photometer with a 1 mA resolution (PHOmo; anthos). Exposure to diagnostic ultrasound biphasically increased the chromogenic activity of a prekallikrein solution in 26% glycerol. About 3-4 min ultrasound at 23 °C generated about 0.02 μg/ml kallikrein, that means that about 1% of pure prekallikrein in glycerol was converted into kallikrein. Thus, diagnostic ultrasound activates purified human prekallikrein to kallikrein. The ultrasound energy seems to fold the latent proenzyme prekallikrein into the active enzyme kallikrein. This contributes to explain the triggering action of ultrasound on the contact system of plasmatic human coagulation. Conversion of only 1% of prekallikrein into kallikrein is absolutely sufficient to start the intrinsic coagulation cascade. The clinical consequence of this action of ultrasound on intrinsic coagulation is that patients at risk for thrombosis, for example, patients with insufficiencies of hepatocytes, AT-3, C1-ina, or fibrinolysis should be protected by low-molecular-weight-heparin prior to the exposure of ultrasound, especially upon its prolonged exposure.

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“…These cytokines increase the expression of tissue factors on vascular endothelial cells, which can induce disorders of the coagulation system . Second, LPS infection can activate the coagulation system and reduce anticoagulation and fibrinolysis functions, which induce the formation of thrombosis . These two ways are enhanced and expanded reciprocally by interacting with each other .…”

Section: Discussionmentioning

confidence: 99%

“…12 Second, LPS infection can activate the coagulation system and reduce anticoagulation and fibrinolysis functions, which induce the formation of thrombosis. 13 These two ways are enhanced and expanded reciprocally by interacting with each other. 3 In the present study, LPS infusion resulted in typical changes of DIC, as evidenced by increases in APTT, PT, FDP, plasma concentrations of TNF-a, ALT and BUN, as well as decreases in plasma FIB, protein C and ATIII.…”

Section: Discussionmentioning

confidence: 99%

Antagonism by salvianolic acid B of lipopolysaccharide‐induced disseminated intravascular coagulation in rabbits

Bai

et al. 2014

Clin Exp Pharma Physio

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The aim of the present study was to investigate the effects of salvianolic acid B on lipopolysaccharide (LPS)-induced disseminated intravascular coagulation (DIC) in rabbits. Continuous infusion of LPS was used to induce a DIC model in rabbits. Treatment with salvianolic acid B (1, 3 or 6 mg/kg) was started simultaneously with LPS infusion (0.5 mg/kg LPS in 60 mL saline; 10 mL/h over a period of 6 h) through the contralateral marginal ear vein. Activated partial thromboplastin time (APTT), prothrombin time (PT), platelet count and fibrinogen concentration were determined, as were plasma levels of fibrin-fibrinogen degradation products (FDP), alanine aminotransferase (ALT), blood urea nitrogen (BUN), protein C activity, antithrombin III (ATIII) and tumour necrosis factor (TNF)-α concentration. The gradual impairment of haemostatic parameters was induced by continuous infusion of LPS. There were marked increases in APTT, PT, BUN, ALT and plasma TNF-α and marked decreases in the platelet count, fibrinogen, FDP, protein C and ATIII. The intravenous administration of 1, 3 or 6 mg/kg salvianolic acid B attenuated the increases in APTT, PT, BUN, ALT and plasma TNF-α and the decreases in fibrinogen, platelet, FDP, protein C and ATIII induced by LPS infusion. These observations indicate that salvianolic acid B has an effect against LPS-induced DIC in rabbits.

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Coagulation Activation by Lipopolysaccharides

Cited by 13 publications

References 99 publications

Fucoidan Extracted from Fucus evanescens Prevents Endotoxin-Induced Damage in a Mouse Model of Endotoxemia

Fucoidan Extracted from Fucus evanescens Prevents Endotoxin-Induced Damage in a Mouse Model of Endotoxemia

Diagnostic ultrasound activates pure prekallikrein

Antagonism by salvianolic acid B of lipopolysaccharide‐induced disseminated intravascular coagulation in rabbits

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