Effects of astaxanthin on blood coagulation, fibrinolysis and platelet aggregation in hyperlipidemic rats

• Published in: Pharmaceutical biology Vol. 55; no. 1; pp. 663 - 672
• Main Authors: Deng, Zu-Yue, Shan, Wei-Guang, Wang, Shen-Feng, Hu, Meng-Mei, Chen, Yan
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01.01.2017; Taylor & Francis Ltd; Taylor & Francis Group
• Subjects: 6-Ketoprostaglandin F1 alpha - blood; Animals; Anticoagulants - pharmacology; antioxidant activity; Aorta; Astaxanthin; Biomarkers - blood; Blood coagulation; Blood Coagulation - drug effects; Blood platelets; Carotenoid; Coronary vessels; Diet, High-Fat; Disease Models, Animal; Dose-Response Relationship, Drug; Enzyme-linked immunosorbent assay; Fibrin; Fibrinolysis; Fibrinolysis - drug effects; Fibrinolytic Agents - pharmacology; Hemostasis; High fat diet; Hyperlipidemias - blood; Hyperlipidemias - drug therapy; Hyperlipidemias - etiology; Hyperlipidemias - genetics; Lipid Peroxidation - drug effects; Lipids - blood; Low density lipoprotein; Male; Membrane proteins; Nitric oxide; Nitric Oxide - blood; Nitric Oxide Synthase Type III - blood; Nitric Oxide Synthase Type III - genetics; Nitric-oxide synthase; NO/ROS balance; P-Selectin - blood; Partial Thromboplastin Time; Plasminogen Activator Inhibitor 1 - genetics; Plasminogen Activator Inhibitor 1 - metabolism; Plasminogen activator inhibitors; Platelet aggregation; Platelet Aggregation - drug effects; Platelet Aggregation Inhibitors - pharmacology; Platelet Function Tests; Polymerase chain reaction; Prostacyclin; Prostaglandins; Proteins; Prothrombin; Prothrombin Time; Rats, Sprague-Dawley; RNA-directed DNA polymerase; Rodents; Superoxide dismutase; t-PA/PAI-1 balance; Thromboplastin; Thromboxane B2 - blood; Time Factors; Tissue Plasminogen Activator - blood; TXA2/PGI2 balance; Xanthophylls; Xanthophylls - pharmacology; TXA2/PGI2 balance; NO/ROS balance; Carotenoid; antioxidant activity; t-PA/PAI-1 balance
• ISSN: 1388-0209; 1744-5116
• DOI: 10.1080/13880209.2016.1261905

Context: 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. Materials and 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.