Endosulfan inducing blood hypercoagulability and endothelial cells apoptosis via the death receptor pathway in Wistar rats†
To investigate the effects of endosulfan on coagulation status and its mechanism, 32 male Wistar rats were randomly divided into four groups, including a control solution and three concentrations of endosulfan groups (1, 5, 10 mg kg−1 per day). The results showed that endosulfan significantly promoted platelet aggregation, prolonged the thrombin time and increased the D-dimer level, and decreased antithrombin III activity and the fibrinogen level. It also significantly enhanced the plasma levels of ROS and vWF, increased the expressions of 8-OHdG and apoptosis positive cells in the endothelial cells and promoted the expressions of Fas, FasL, caspase-8, and caspase-3 in vascular endothelial cells. The results suggested that endosulfan could cause the hypercoagulability of blood by promoting both platelet aggregation and the transformation of fibrinogen into fibrin, as well as depressing antithrombin III activity. Furthermore, endosulfan could induce the dysfunction of endothelial cells by causing apoptosis via a death receptor pathway, resulting from oxidative stress, which could be one of the key mechanisms behind hypercoagulability induced by endosulfan.