Doxorubicin-induced vascular toxicity--targeting potential pathways may reduce procoagulant activity

Previous study in mice using real-time intravital imaging revealed an acute deleterious effect of doxorubicin (DXR) on the gonadal vasculature, as a prototype of an end-organ, manifested by a reduction in blood flow and disintegration of the vessel wall. We hypothesized that this pattern may represe...

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Bibliographic Details
Published in:PloS one 2013-09, Vol.8 (9), p.e75157
Main Authors: Ben Aharon, Irit, Bar Joseph, Hadas, Tzabari, Moran, Shenkman, Boris, Farzam, Nahid, Levi, Mattan, Shalgi, Ruth, Stemmer, Salomon M, Savion, Naphtali
Format: Article
Language:English
Subjects:
Adenosine diphosphate
Adhesion
Agglomeration
Animals
Anthracyclines
Antibiotics, Antineoplastic - toxicity
Anticoagulants
Anticoagulants - pharmacology
Aorta - cytology
Aorta - drug effects
Aorta - metabolism
Biochemistry
Biocompatibility
Blood
Blood flow
Blood Flow Velocity - drug effects
Blood platelets
Cancer therapies
Chemotherapy
Coagulants
Developmental biology
Disintegration
Doppler effect
Doxorubicin
Doxorubicin - toxicity
Endothelial cells
Endothelium
Endothelium, Vascular - cytology
Endothelium, Vascular - drug effects
Endothelium, Vascular - metabolism
Enoxaparin - pharmacology
Heart attacks
Heparin
Image Processing, Computer-Assisted
Immunoenzyme Techniques
In vivo methods and tests
Laboratories
Low molecular weight heparin
Low molecular weights
Male
Mediation
Medicine
Metastasis
Mice
Mice, Inbred ICR
Molecular weight
Peptides - pharmacology
Platelet Adhesiveness - drug effects
Platelet aggregation
Platelet Aggregation - drug effects
Platelet Aggregation Inhibitors - pharmacology
Platelet Glycoprotein GPIIb-IIIa Complex - antagonists & inhibitors
Platelets
Real time
Respiration
Testes
Thromboembolism
Toxicity
Ultrasonography, Doppler
Ultrasound
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Summary:Previous study in mice using real-time intravital imaging revealed an acute deleterious effect of doxorubicin (DXR) on the gonadal vasculature, as a prototype of an end-organ, manifested by a reduction in blood flow and disintegration of the vessel wall. We hypothesized that this pattern may represent the formation of microthrombi. We aimed to further characterize the effect of DXR on platelets' activity and interaction with endothelial cells (EC) and to examine potential protectants to reduce DXR acute effect on the blood flow. The effect of DXR on platelet adhesion and aggregation were studied in vitro. For in vivo studies, mice were injected with either low molecular weight heparin (LMWH; Enoxaparin) or with eptifibatide (Integrilin(©)) prior to DXR treatment. Testicular arterial blood flow was examined in real-time by pulse wave Doppler ultrasound. Platelet treatment with DXR did not affect platelet adhesion to a thrombogenic surface but significantly decreased ADP-induced platelet aggregation by up to 40% (p
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0075157