Alva-Chavarría Denys, Soto-Núñez Maribel, Flores-Soto Edgar, Jaimez Ruth
Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico.
Life (Basel). 2023 Jul 23;13(7):1612. doi: 10.3390/life13071612.
This study aimed to explore the effects of raloxifene (Rx) and estradiol (E) on prothrombin time (PT), partial thromboplastin time (APTT), coagulation factors (VII, X, XI), and fibrinogen concentrations in rats. Female rats were ovariectomized 11 days prior to starting the treatment. Afterward, they received Rx or E (1, 10, 100, and 1000 µg/kg) or propylene glycol (0.3 mL; vehicle, V) subcutaneously for 3 consecutive days. Plasma was collected to measure the hemostatic parameters. Rx significantly increased PT (8%, at 1000 µg/kg; < 0.05) and APTT at all doses evaluated (32, 70, 67, 30%; < 0.05, respectively). Rx (1, 10, 100, and 1000 µg/kg) decreased the activity of factor VII by -20, -40, -37, and -17% ( < 0.05), respectively, and E increased it by 9, 34, 52, and 29%. Rx reduced factor X activity at 10 and 100 µg/kg doses (-30, and -30% < 0.05), and E showed an increment of 24% with 1000 µg/kg dose only. Additionally, Rx (1, 10, 100 µg/kg) diminished FXI activity (-71, -62, -66; < 0.05), E (1 and 10 µg/kg) in -60 and -38, respectively ( < 0.05), and Rx (1000 µg/kg) produced an increment of 29% ( < 0.05) in fibrinogen concentration, but not E. Our findings suggest that raloxifene has a protective effect on hemostasis in rats.
本研究旨在探讨雷洛昔芬(Rx)和雌二醇(E)对大鼠凝血酶原时间(PT)、部分凝血活酶时间(APTT)、凝血因子(VII、X、XI)及纤维蛋白原浓度的影响。在开始治疗前11天,对雌性大鼠进行卵巢切除术。之后,它们连续3天皮下注射Rx或E(1、10、100和1000μg/kg)或丙二醇(0.3mL;赋形剂,V)。收集血浆以测量止血参数。Rx在所有评估剂量下均显著增加PT(1000μg/kg时增加8%;P<0.05)和APTT(分别为32%、70%、67%、30%;P<0.05)。Rx(1、10、100和1000μg/kg)分别使因子VII的活性降低-20%、-40%、-37%和-17%(P<0.05),而E使其增加9%、34%、52%和29%。Rx在10和100μg/kg剂量下降低因子X的活性(-30%和-30%,P<0.05),而E仅在1000μg/kg剂量下使因子X活性增加24%。此外,Rx(1、10、100μg/kg)降低FXI活性(-71%、-62%、-66%;P<0.05),E(1和10μg/kg)分别降低-60%和-38%(P<0.05),Rx(1000μg/kg)使纤维蛋白原浓度增加29%(P<0.05),而E则无此作用。我们的研究结果表明,雷洛昔芬对大鼠止血具有保护作用。