BACKGROUND/AIMS: 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. Copyright 2008 S. Karger AG, Basel.
BACKGROUND/AIMS: 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. Copyright 2008 S. Karger AG, Basel.
Authors: Robert G Fassett; Helen Healy; Ritza Driver; Iain K Robertson; Dominic P Geraghty; James E Sharman; Jeff S Coombes Journal: BMC Nephrol Date: 2008-12-18 Impact factor: 2.388
Authors: Dale A Lauver; Dawn S Kuszynski; Barbara D Christian; Matthew P Bernard; James P Teuber; Bruce E Markham; Yuqing E Chen; Haoming Zhang Journal: Pharmacol Res Perspect Date: 2019-07-25