Moreschi Bruna Pache, da Silva Portilho Romário, Santos Andreza Negreli, Brito Igor Leal, Otsubo Jaques Jeandre Augusto
Biochemistry Sector, Institute of Biosciences, Federal University of Mato Grosso Do Sul (UFMS), Campo Grande, Mato Grosso Do Sul, 79070-900, Brazil.
Graduate Program in Pharmaceutical Sciences, UFMS, Campo Grande, Mato Grosso Do Sul, 79070-900, Brazil.
Purinergic Signal. 2025 Feb 27. doi: 10.1007/s11302-025-10075-w.
Hormonal contraceptives, one of the most widely used contraceptive methods, are associated with the development of thromboembolism. Purinergic mediators such as soluble agonists, ectonucleotidases, and receptors play a prominent role in regulating hemostasis. This study aimed to evaluate E-NTPDase, E-5'-NT, and E-ADA activities in lymphocytes and platelets from women using combined oral contraceptives. Participants used third-generation (3G) oral contraceptives, such as drospirenone or cyproterone acetate, or fourth-generation (4G) oral contraceptives, such as gestodene or desogestrel, both combined with ethinylestradiol. The findings indicated decreased adenosine (ADO) deamination in lymphocytes (78%, p < 0.001) and decreased AMP hydrolysis (69%, p < 0.01) and ADO deamination (66%, p < 0.001) in platelets from women using 3G contraceptives compared with the control. Furthermore, the results showed decreased ADO deamination (66%, p < 0.05) in lymphocytes and decreased ATP hydrolysis (52%, p < 0.05) and decreased ADO deamination (57%, p < 0.001) in platelets from women using 4G contraceptives compared with the control. The observed patterns of AMP hydrolysis are compatible with an ADO-poor vascular microenvironment. Likewise, the decrease in E-ADA activity may be associated with lower concentrations of ADO in the vascular microenvironment, which has antiplatelet and anti-inflammatory effects. Overall, the findings demonstrated that hormonal contraceptives alter the activity of purinergic ectoenzymes, which might be related to their effects on hemostasis and a predisposition to thromboembolic events.
激素避孕法是使用最为广泛的避孕方法之一，与血栓栓塞的发生有关。嘌呤能介质，如可溶性激动剂、外核苷酸酶和受体，在调节止血过程中发挥着重要作用。本研究旨在评估使用复方口服避孕药的女性淋巴细胞和血小板中的E-NTPDase、E-5'-NT和E-ADA活性。参与者使用第三代（3G）口服避孕药，如屈螺酮或醋酸环丙孕酮，或第四代（4G）口服避孕药，如孕二烯酮或去氧孕烯，均与炔雌醇联合使用。研究结果表明，与对照组相比，使用3G避孕药的女性淋巴细胞中的腺苷（ADO）脱氨基作用降低（78%，p<0.001），血小板中的AMP水解降低（69%，p<0.01）和ADO脱氨基作用降低（66%，p<0.001）。此外，结果显示，与对照组相比，使用4G避孕药的女性淋巴细胞中的ADO脱氨基作用降低（66%，p<0.05），血小板中的ATP水解降低（52%，p<0.05）和ADO脱氨基作用降低（57%，p<0.001）。观察到的AMP水解模式与缺乏ADO的血管微环境相符。同样，E-ADA活性的降低可能与血管微环境中较低浓度的ADO有关，ADO具有抗血小板和抗炎作用。总体而言，研究结果表明激素避孕药会改变嘌呤能外切酶的活性，这可能与其对止血的影响以及血栓栓塞事件的易感性有关。
