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 journalArticle

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

Fingerprint

Hemostatics
Vascular Diseases
Aspirin
Biomarkers
Blood Platelets
Prodrugs
Fibrinolysis
Hemostasis
Platelet Membrane Glycoprotein IIb
Thrombin Time
P-Selectin
Antithrombin III
Plasminogen
Protein S
Prothrombin Time
von Willebrand Factor
Carotenoids
Protein C
Nervous System Diseases
Platelet Aggregation

Keywords

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

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

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. / Serebruany, Victor; Malinin, Alex; Goodin, Thomas; Pashkow, Fredric.

In: American Journal of Therapeutics, Vol. 17, No. 2, 03.2010, p. 125-132.

Research output: Contribution to journalArticle

@article{74fc453d67174d49b7b9b6b10974abfc,
title = "The in vitro effects of xancor, a synthetic astaxanthine derivative, on hemostatic biomarkers in aspirin-na{\"i}ve and aspirin-treated subjects with multiple risk factors for vascular disease",
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-na{\"i}ve 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-na{\"i}ve 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.",
keywords = "Antioxidant, Aspirin, Astaxanthine, Cardiovascular, Coagulation, Fibrinolysis, In vitro, Platelets, Risk factors",
author = "Victor Serebruany and Alex Malinin and Thomas Goodin and Fredric Pashkow",
year = "2010",
month = "3",
doi = "10.1097/MJT.0b013e31819cdbbd",
language = "English (US)",
volume = "17",
pages = "125--132",
journal = "American Journal of Therapeutics",
issn = "1075-2765",
publisher = "Lippincott Williams and Wilkins",
number = "2",

}

TY - JOUR

T1 - 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

AU - Serebruany, Victor

AU - Malinin, Alex

AU - Goodin, Thomas

AU - Pashkow, Fredric

PY - 2010/3

Y1 - 2010/3

N2 - 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.

AB - 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.

KW - Antioxidant

KW - Aspirin

KW - Astaxanthine

KW - Cardiovascular

KW - Coagulation

KW - Fibrinolysis

KW - In vitro

KW - Platelets

KW - Risk factors

UR - http://www.scopus.com/inward/record.url?scp=77949967825&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77949967825&partnerID=8YFLogxK

U2 - 10.1097/MJT.0b013e31819cdbbd

DO - 10.1097/MJT.0b013e31819cdbbd

M3 - Article

C2 - 20305399

AN - SCOPUS:77949967825

VL - 17

SP - 125

EP - 132

JO - American Journal of Therapeutics

JF - American Journal of Therapeutics

SN - 1075-2765

IS - 2

ER -