Effects of defibrotide on leukocytosis in rabbits with diet-induced atherosclerosis

Pescador, Rodolfo; Tettamanti, R; Salvetti, Laura; Conto, A.; Barone, Domenico; Porta, Roberto; Mantovani, M; Ferro, Laura

doi:10.1016/0024-3205(95)00308-s

Cited by 6 publications

(5 citation statements)

References 27 publications

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“…The anti-atherosclerotic activity of DFT was mainly described by Pescador (Pescador et al, 1989;Pescador et al, 1995), Schrör (Schror et al, 1989) and Porta (Porta et al, 1994). Kahan (Ferraresso et al, 1993) and Ferrero (Ferrero et al, 1994) discovered and described DFT anti-rejection activity.…”

Section: The History Of Defibrotidementioning

confidence: 99%

“…Schrör (Bracht and Schror, 1994;Schror, 1985, 1989), and Pescador (Pescador et al, 1995) found an evidence of antiplatelet activity of DFT, while Schrör (Hohlfeld et al, 1993;Schror et al, 1989), Lefer (Scalia et al, 1996a) and Rossoni (Rossoni et al, 1996) described its anti polymorphonucleate leukocyte (PMN) activity. Fumagalli, Pescador and Kahan discovered DFT anti leukocyte activity (Ferraresso et al, 1993;Fumagalli et al, 1987;Fumagalli et al, 1989;Pescador et al, 1995). As far as DFT activities at molecular level are concerned, we have to quote the seminal work of Niada, who first suggested that DFT increases the generation of prostacyclin I 2 (PGI 2) (Niada et al, 1981).…”

Section: The History Of Defibrotidementioning

confidence: 99%

“…DFT deactivates platelets (Bracht and Schror, 1994), monocyte/macrophages (Cirillo et al, 1991;Tettamanti et al, 1992) and PMNs (Hohlfeld et al, 1991;Scalia et al, 1996a;Schror et al, 1989;Shin et al, 1998). Leukocytosis and thrombocytosis are decreased by DFT (Pescador et al, 1995). DFT decreases leukocyte and platelet aggregates in thrombi (Fumagalli et al, 1987;Fumagalli et al, 1989).…”

Section: Change In Phenotype From Anti-thrombotic To Pro-thromboticmentioning

confidence: 99%

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Defibrotide: Properties and clinical use of an old/new drug

Pescador

Capuzzi

Mantovani

et al. 2013

Vascular Pharmacology

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105

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The drug named defibrotide (DFT) has been studied for many years. It has been shown to possess many activities: profibrinolytic, antithrombotic-thrombolytic, antiischemic (heart, liver, kidney, skin, brain), antishock, antiatherosclerotic, antirejection and anti-angiogenic. The previously displayed activities, as antithrombotic, profibrinolytic and anti-inflammatory, suggested its use in vascular disorders, as in the treatment of peripheral obliterative arterial disease and in thrombophlebitis. Some years after, the use of DFT in hepatic veno-occlusive disease has been also proposed. Even if DFT was considered for long time a multi-target drug, now it could be considered on the whole as a drug able to protect endothelium against activation. The present work reviews the more important experimental and clinical studies performed to detect DFT effects.

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Section: The History Of Defibrotidementioning

confidence: 99%

Section: The History Of Defibrotidementioning

confidence: 99%

Section: Change In Phenotype From Anti-thrombotic To Pro-thromboticmentioning

confidence: 99%

See 1 more Smart Citation

Defibrotide: Properties and clinical use of an old/new drug

Pescador

Capuzzi

Mantovani

et al. 2013

Vascular Pharmacology

Self Cite

105

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show abstract

“…Defibrotide has been studied as an anti-coagulation and endothelial protection agent in different rat models. In those studies, defibrotide was given by different routes of administration and at different dosages in different animals [ 22 – 24 ]. For example, Kim et al [ 25 ] examined the effect of defibrotide on liver ischemia-reperfusion injury.…”

Section: Discussionmentioning

confidence: 99%

Defibrotide improved the outcome of monocrotaline induced rat hepatic sinusoidal obstruction syndrome

et al. 2022

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Background and aim Pyrrolizidine alkaloids (PA) induced hepatic sinusoidal obstruction syndrome (HSOS) occurred worldwide and the mortality rate remained high because there were no specific therapies. Defibrotide was effective for HSOS following hematopoietic stem cell transplantation. But the pathogenesis of the two types of HSOS were not equivalent. The purpose of this study was to see if defibrotide was also effective in PA induced rat HSOS. Methods First we improved rat HSOS model by using higher dose (230 mg/kg) of monocrotaline (a kind of PA) as the dose of median lethal dose. So drug effectiveness could be assessed by survival time. Next, male SD rats were divided into 5 groups. They were control group, model group, low dose low molecular weight heparin (LMWH) treatment group, high dose LMWH treatment group and defibrotide treatment group. Rats’ survival time, liver function, white blood cell count and cytokines were compared among the groups. The DeLeve score was used to assess the severity of liver pathology. Results The model group exhibited typical liver pathology of HSOS, such as hepatic sinus dilation, congestion, endothelial injury of central lobular vein, coagulative necrosis of hepatocytes and fibrin deposition in the subendothelial. The pathologic characteristics indicated that the model was built up successfully. The survival rate was significantly higher in defibrotide group (81.8%) than model group (43.7%), while the survival rates were similar in the two LMWH groups (62.5% and 75%) and model group. The survival time only be prolonged by defibrotide (P=0.028) but not LMWH (P>0.05). DeLeve score was improved most in the defibrotide group than the two LMWH groups (both P<0.01). Changes in DeLeve score, liver function, plasma level of tumor necrosis factor α and plasminogen activator inhibitor-1 exhibited the same trends. Conclusion Defibrotide could improve the outcome of monocrotaline-induced rat HSOS indicating that defibrotide might be a better choice than LMWH in clinical practice.

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“…DFT deactivates platelets (11), monocyte/macrophages (18,78), and PMNs (12,37,75). Leukocytosis and thrombocytosis are decreased by DFT (60). DFT decreases leukocyte and platelet aggregates in thrombi (28,29).…”

Section: Change In Phenotype From Antithrombotic To Prothromboticmentioning

confidence: 99%

Defibrotide and Endothelial Cell Activation

Pescador¹,

Porta²,

Ferro³

2000

Cardiovascular Drug Reviews

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Defibrotide has several activities [profibrinolytic, antithrombotic-thrombolytic, antiischemic (heart, liver, kidney, skin, brain), antishock, antiatherosclerotic, and antirejection]. This host of activities has puzzled several people accustomed to the concept: one drug -one activity. But, if you see defibrotide as an antiendothelial cell activation drug, each piece of the puzzle will neatly fit into its right place and the host of activities becomes an array of activities. In fact the polyhedric inflammatory process is the common background of seemingly different illnesses, both acute and chronic. So the old concept of one drug-one activity proves true; one drug: defibrotide -one activity; antiendothelial cell activation activity.

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Effects of defibrotide on leukocytosis in rabbits with diet-induced atherosclerosis

Cited by 6 publications

References 27 publications

Defibrotide: Properties and clinical use of an old/new drug

Defibrotide: Properties and clinical use of an old/new drug

Defibrotide improved the outcome of monocrotaline induced rat hepatic sinusoidal obstruction syndrome

Defibrotide and Endothelial Cell Activation

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