Disodium disuccinate astaxanthin prevents carotid artery rethrombosis and ex vivo platelet activation.
OBJECTIVE
The disodium disuccinate derivative of astaxanthin (DDA) is a carotenoid antioxidant under development for the treatment of ischemic cardiovascular events. Recent evidence suggests that reactive oxygen species (ROS) play an important role in platelet activation. This study seeks to investigate the effects of a reactive oxygen species quencher, DDA, in a canine model of carotid artery thrombosis.


METHODS
After formation of an occlusive carotid thrombus, dogs were administered recombinant tissue plasminogen activator intra-arterially to achieve thrombolysis in the presence of either 0.9% NaCl solution or DDA (10-50 mg/kg i.v. infusion). Ex vivo platelet aggregation and tongue bleeding times were measured before and after drug administration. Residual thrombus mass was analyzed at the end of each experiment.


RESULTS
The data indicated a dose- dependent reduction in the incidence of carotid artery rethrombosis. In addition, platelet aggregation and thrombus weights were dose-dependently inhibited by DDA. No change was recorded in tongue bleeding time among the treatment groups.


CONCLUSIONS
The data demonstrate that at the doses used in this study, DDA significantly reduced the incidence of secondary thrombosis while maintaining normal hemostasis. The results suggest that upon further study, DDA may one day find utility in revascularization procedures.
Lauver
D Adam
DA
Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Mich 48109, USA.
Driscoll
Edward M
EM
Lucchesi
Benedict R
BR
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D001760:Bleeding Time; D002341:Carotid Artery Thrombosis / Q000097:blood / Q000517:prevention & control*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D007262:Infusions, Intravenous; D008297:Male; D015539:Platelet Activation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D013386:Succinates / Q000494:pharmacology / Q000627:therapeutic use*; D010959:Tissue Plasminogen Activator / Q000494:pharmacology; D014059:Tongue / Q000098:blood supply; D024341:Xanthophylls / Q000494:pharmacology / Q000627:therapeutic use*
D000975:Antioxidants; D010975:Platelet Aggregation Inhibitors; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D013386:Succinates; D024341:Xanthophylls; C476770:succinic acid mono-(4-(18-(4-(3-carboxypropionyloxy)-2,6,6-trimethyl-3-oxocyclohex-1-enyl)-3,7,12,16-tetramethyloctadeca-1,3,5,7,9,11,13,15,17-nonaenyl)-3,5,5-trimethyl-2-oxocyclohex-3-enyl) ester; D010959:Tissue Plasminogen Activator