title: Endosulfan activates the extrinsic coagulation pathway by inducing endothelial cell injury in rats.
abstract: Endosulfan, a persistent organic pollutant, is widely used in agriculture as a pesticide. The aim of the present study was to evaluate the blood toxicity of different doses of endosulfan in Wistar rats. The experimental sample was composed of four groups, a control group that did not receive endosulfan and three endosulfan-exposed groups that respectively received 1, 5, or 10 mg/kg/day (doses below LD50), of endosulfan for 21 days. The results showed that endosulfan significantly decreased the prothrombin time (PT) and upregulated the activated coagulation factors VIIa, Xa, and XIIIa; thrombin-antithrombin complex (TAT); and P-selectin. Plasma levels of tissue factor (TF) and malondialdehyde (MDA) were increased in the endosulfan groups. The activated partial thromboplastin time (APTT) and the level of activated coagulation factor IXa showed no obvious changes. Immunohistochemical results showed increased expression of von Willebrand factor (vWF) and the inflammatory cytokine interleukin (IL)-1β in the groups exposed to endosulfan. The pathology and electron microscopy results showed impaired vascular tissue accompanied by the exfoliation of endothelial cells and mitochondrial damage in the endosulfan-exposed groups. In summary, our results suggest that endosulfan damages endothelial cells via oxidative stress and the inflammatory response, leading to the release of TF and vWF into the blood. The TF and vWF in the blood may activate extrinsic coagulation factors and platelets, thus triggering the extrinsic coagulation pathway. There were no obvious effects on the intrinsic coagulation pathway.
authors.affiliation: Department of Toxicology and Hygienic Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, China.|Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China.
authors.forename: Lianshuang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Toxicology and Hygienic Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, China.|Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China.
authors.forename: Jialiu
authors.initials: J
authors.lastname: Wei
authors.affiliation: Department of Toxicology and Hygienic Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, China.|Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China.
authors.forename: Fangzi
authors.initials: F
authors.lastname: Guo
authors.affiliation: Department of Toxicology and Hygienic Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, China.|Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China.
authors.forename: Junchao
authors.initials: J
authors.lastname: Duan
authors.affiliation: Department of Toxicology and Hygienic Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, China.|Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China.
authors.forename: Yanbo
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Toxicology and Hygienic Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, China.|Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China.
authors.forename: Zhixiong
authors.initials: Z
authors.lastname: Shi
authors.affiliation: Department of Toxicology and Hygienic Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, China.|Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Toxicology and Hygienic Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, China. xqzhou@ccmu.edu.cn.|Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China. xqzhou@ccmu.edu.cn.
authors.forename: Xianqing
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Toxicology and Hygienic Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, China.|Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Sun
mesh_terms: D000818:Animals; D000990:Antithrombin III / Q000378:metabolism; D001777:Blood Coagulation / Q000187:drug effects*; D001779:Blood Coagulation Factors / Q000378:metabolism; D004726:Endosulfan / Q000633:toxicity*; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D010447:Peptide Hydrolases / Q000378:metabolism; D010575:Pesticides / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013925:Thromboplastin / Q000378:metabolism
chemical_list: D001779:Blood Coagulation Factors; D010575:Pesticides; C046193:antithrombin III-protease complex; D000990:Antithrombin III; D013925:Thromboplastin; D010447:Peptide Hydrolases; D004726:Endosulfan
keywords: Coagulation pathway; Endosulfan; Endothelial cell; Mechanism; Rats; vWF