The in vitro effects of xancor, a synthetic astaxanthine derivative, on hemostatic biomarkers in aspirin-naïve and aspirin-treated subjects with multiple risk factors for vascular disease

Victor Serebruany, Alex Malinin, Thomas Goodin, Fredric Pashkow

Research output: Contribution to journalArticlepeer-review

Abstract

Astaxanthine is a polar carotenoid metabolite derived from a proprietary prodrug, Xancor, which aligns parallel with the membrane phospholipids exhibiting potent antioxidant, anti-inflammatory, and cell protective properties, although the precise mechanism of action is unknown. This prodrug is currently under development for hepatic, neurologic, and vascular disease indications. Considering established links between heart disease and stroke with platelets, coagulation cascade, and fibrinolysis, the aim of the study was to assess the effect of asthaxantine on human biomarkers of hemostasis. The rationale was to test a hypothesis that the drug may diminish activation of hemostasis, making it a potentially attractive addition to treat patients with vascular disease. In vitro effects of whole blood preincubation with escalating concentrations of asthaxantine (0.3 μM, 1 μM, 3 μM, 10 μM, 30 μM, and 100 μM) were assessed from 12 aspirin-naïve and eight aspirin-treated volunteers with multiple risk factors for vascular disease. A total of 25 biomarkers were measured, of which 12 were related to platelet function, 10 to coagulation, and three to fibrinolysis. Platelet aggregation induced by ADP, collagen, and arachidonic acid and expression of CD31, CD41, GP IIb/IIIa, CD51/61, P-selectin, CD63, CD107a, CD151+CD14, and CD154 were not affected. Coagulation indices such as aPTT, prothrombin time, thrombin time, fibrinogen, antithrombin III (antigen and activity), Protein C, Protein S (free and activity), and von Willebrand factor remained unchanged after incubation with astaxanthine. Fibrinolytic activity biomarkers such as plasminogen, D-dimer, and FDP were also not affected after in vitro pretreatment of blood samples with astaxanthine. In the projected subclinical (less than 1 μM), therapeutic (3 μM to 30 μM), and supratherapeutic concentration (100 μM), astaxanthine in vitro does not affect platelet, coagulation, or fibrinolytic indices in either aspirin-naïve or aspirin-treated subjects. These results are important for the assessment of the safety profile, but remain to be confirmed preclinically, in vivo, and ultimately in the clinic.

Original languageEnglish (US)
Pages (from-to)125-132
Number of pages8
JournalAmerican Journal of Therapeutics
Volume17
Issue number2
DOIs
StatePublished - Mar 2010

Keywords

  • Antioxidant
  • Aspirin
  • Astaxanthine
  • Cardiovascular
  • Coagulation
  • Fibrinolysis
  • In vitro
  • Platelets
  • Risk factors

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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