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Suledoxide Mediated Inhibition of Tissue Factor Activation of Platelet. A Potential Mechanism for the Observed Therapeutic Effects in Diabetic Nephropathy
Author(s) -
Adiguzel Cafer,
Iqbal Omer,
Debra Hoppensteadt,
Cunanan Josephine,
Fareed Jawed
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1118.9
Subject(s) - platelet , chemistry , platelet activation , tissue factor , pharmacology , heparin , platelet activating factor , diabetic nephropathy , nephropathy , platelet factor 4 , hirudin , thrombin , endocrinology , medicine , coagulation , diabetes mellitus , biochemistry
Suledoxide (Alfa Wassermann, Bologna) is used for the management of cardiovascular disorders and has been developed in the United States for the treatment of diabetic nephropathy. Suledoxide is composed of 80% fast moving heparin and 20% dermatan sulfate resulting in a lower anticoagulant effect in comparison to unfractionated heparin. To investigate Suledoxide's effect on platelet function, studies were carried out to characterize its effects on agonist induced platelet aggregation and tissue factor (TF)‐induced activation of platelets. Supplementation of Suledoxide to platelet rich plasma did not alter ADP, epinephrine, and collagen‐induced platelet aggregation. However Suledoxide inhibited TF‐mediated microparticle formation (IC 50 =3.5 μg/ml), platelet aggregate formation (IC 50 =7.5 μg/ml), and P‐ selectin expression (IC 50 =4.0 μg/ml). Another heparinoid, Danaparoid, inhibited microparticle formation (IC 50 =3.5 μg/ml) but did not inhibit P‐selectin expression and platelet aggregate formation. These results suggest that while Suledoxide exhibits a lower anticoagulant effect, it still capable of inhibiting TF‐mediated platelet activation. This effect may contribute to the observed therapeutic effects of Suledoxide in diabetic nephropathy. These results also suggest that inhibition of TF activation of platelets by Suledoxide may be independent of its anticoagulant effects.