Effects of Bisphenol A and S on blood coagulation: in vivo, in vitro and in silico approaches in toxicodynamic.

Bisphenol A (BPA) is a well-known endocrine disruptor with several effects on mammalian systems and has been linked to diseases, such as cancer. Bisphenol S (BPS) emerged as a likely alternative to BPA in industrial production. Despite being well studied and exhibiting BPA-like toxic capacity, many effects are still being elucidated. The blood coagulation system is well controlled in an effort to minimize blood loss. To our knowledge, no study reported actions of bisphenols in this system. The aim of this work was to evaluate the effects of bisphenols on blood coagulation. Zebrafish were used to measure bleeding time. To assess possible mechanisms, platelet-rich plasma was incubated with both bisphenols in the presence of arachidonic acid. Prothrombin time (PT) and activated partial thromboplastin time (APTT) assays were performed in the presence of BPA and BPS. Alignment of human factor VII sequence was compared to zebrafish and docking simulations performed with FVIIa and bisphenols. An extended time was observed in BPA-treated but not BPS-treated animals in bleeding time; in PT, bisphenols showed no effect. APTT was increased in the highest concentration of bisphenols, with no effects in platelet aggregation, indicating interference with factor VII. Protein alignment showed that both proteins have well conserved residues, as those being required for interaction of FVIIa-BPA and FVIIa-BPS complexes, as shown in molecular docking. Taken together, these data show BPA and BPS as capable of interfering with the coagulation process via FVIIa.