title: Effects of astaxanthin on blood coagulation, fibrinolysis and platelet aggregation in hyperlipidemic rats.
abstract: BACKGROUND
  Astaxanthin (ASTX) is a xanthophyll carotenoid that reduces hemostasis in hyperlipidemic organisms. Its antihemostatic mechanisms remain unclear.
  
  
  OBJECTIVE
  The effects of ASTX on coagulation, the fibrinolytic system and platelet aggregation were investigated in hyperlipidemic rats.
  
  
  METHODS
  Different doses of ASTX (5, 10 and 30 mg/kg/day, p.o.) were administered for four weeks to high-fat diet-induced hyperlipidemic rats. Serum lipid and lipoprotein levels were measured with an automatic biochemical analyzer. The prothrombin time (PT), activated partial thromboplastin time (APTT) and maximum platelet aggregation rate (MAR) were determined by a coagulation analyzer. The activities of the tissue-type plasminogen activator (t-PA), type-1 plasminogen activator inhibitor (PAI-1) and endothelial nitric oxide synthase (eNOS), as well as the levels of thromboxane B(2) [TXB(2)], 6-keto prostaglandin F(1α) [6-keto-PGF(1α)] and platelet granule membrane protein (GMP-140), were measured with enzyme-linked immunosorbent assay kits. Gene and protein expression levels were analyzed by reverse transcriptase polymerase chain reaction and Western blot, respectively.
  
  
  RESULTS
  ASTX (30 mg/kg) treatment in hyperlipidemic rats reduced serum TG (0.58 ± 0.14 versus 1.12 ± 0.24 mmol/L), serum TC (1.77 ± 0.22 versus 2.24 ± 0.21 mmol/L), serum LDL-C (1.13 ± 0.32 versus 2.04 ± 0.48 mmol/L), serum MDA (69%), plasma MAR (55%), serum TXB2/6-keto-PGF1α (34%) and serum GMP-140 levels (25%), plasma PAI-1 activity (48%) and downregulated the mRNA (33%) and protein (23%) expression of aorta eNOS, the mRNA (79%) and protein (72%) expression levels of aorta PAI-1. However, ASTX (30 mg/kg/d) treatment increased serum SOD activity (2.1 fold), serum GPx activity (1.8 fold), plasma PT (1.3 fold), plasma APTT (1.7 fold), serum NO (1.4-fold), serum 6-keto-PGF1α (1.3 fold).
  
  
  CONCLUSIONS
  ASTX reduced blood coagulation and platelet aggregation and promoted fibrinolytic activity in hyperlipidemic rats. These activities were closely correlated with ASTX, maintaining the balance of t-PA/PAI-1, NO/ROS and TXA2/PGI2 in vivo.
authors.affiliation: a College of Pharmaceutical Science , Zhejiang University of Technology , Hangzhou , China.|b Zhejiang Institute for Food and Drug Control , Hangzhou , China.
authors.forename: Zu-Yue
authors.initials: ZY
authors.lastname: Deng
authors.affiliation: a College of Pharmaceutical Science , Zhejiang University of Technology , Hangzhou , China.
authors.forename: Wei-Guang
authors.initials: WG
authors.lastname: Shan
authors.affiliation: a College of Pharmaceutical Science , Zhejiang University of Technology , Hangzhou , China.
authors.forename: Shen-Feng
authors.initials: SF
authors.lastname: Wang
authors.affiliation: a College of Pharmaceutical Science , Zhejiang University of Technology , Hangzhou , China.
authors.forename: Meng-Mei
authors.initials: MM
authors.lastname: Hu
authors.affiliation: a College of Pharmaceutical Science , Zhejiang University of Technology , Hangzhou , China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation / Q000187:drug effects*; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005342:Fibrinolysis / Q000187:drug effects*; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006949:Hyperlipidemias / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics; D015227:Lipid Peroxidation / Q000187:drug effects; D008055:Lipids / Q000097:blood; D008297:Male; D009569:Nitric Oxide / Q000097:blood; D052250:Nitric Oxide Synthase Type III / Q000097:blood / Q000235:genetics; D019007:P-Selectin / Q000097:blood; D010314:Partial Thromboplastin Time; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010979:Platelet Function Tests; D011517:Prothrombin Time; D017207:Rats, Sprague-Dawley; D013929:Thromboxane B2 / Q000097:blood; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000097:blood; D024341:Xanthophylls / Q000494:pharmacology
chemical_list: D000925:Anticoagulants; D015415:Biomarkers; D005343:Fibrinolytic Agents; D008055:Lipids; D019007:P-Selectin; D017395:Plasminogen Activator Inhibitor 1; D010975:Platelet Aggregation Inhibitors; D024341:Xanthophylls; D009569:Nitric Oxide; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; C005948:astaxanthine; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D010959:Tissue Plasminogen Activator
keywords: Carotenoid; NO/ROS balance; TXA2/PGI2 balance; antioxidant activity; t-PA/PAI-1 balance