Sodium dehydroacetate induces coagulation aberration via inhibiting liver vitamin K epoxide reductase complex subunit 1 in Wistar rats
Sodium dehydroacetate(Na-DHA),an agent against the growth of bacteria,fungi and yeast,is used as a preservative in food,animal feeds and cosmetics.Previously,we have reported that Na-DHA induced coagulation aberration in Wistar rats.However,the anticoagulant mechanism of Na-DHA is not clear now.Here we showed that Na-DHA prolonged prothrombin time(PT)and activated partial thromboplastin time(APTT)in male and female Wistar rats.In addition,Na-DHA decreased vitamin K(VK)level and increased protein induced by vitamin K absence/antagonist-Ⅱ(PIVKA-Ⅱ)level in serum of rats.Moreover,we found that administration with VK not only reversed Na-DHA-decreased serum VK and-increased PIVKA-Ⅱ level,but also attenuated Na-DHA-prolonged PT and APTT,suggesting that Na-DHA-decreased serum VK level contributed to coagulation aberration.Further we revealed that Na-DHA inhibited vitamin K epoxide reductase complex subunit 1(VKORC1),a key enzyme in VK recycling,in liver of Wistar rats.This was evidenced by findings that Na-DHA decreased mRNA and protein level of VKORC1.Taken together,our data indicate that Na-DHA inhibited liver VKORC1 results in decrease of serum VK level,leading to coagulation aberration in rats.
Na-DHA anticoagulation VKORC1 VK liver Wistar rat
Xin Chen Qianhan Wei Qianqian Lu Zeting Zhao Zhengrong Yu Yumei Zhang
Department of Veterinary Pharmacology and Toxicology,College of Veterinary Medicine,Yangzhou Univers Department of Veterinary Pharmacology and Toxicology,College of Veterinary Medicine,Yangzhou Univers
国内会议
江苏扬州
英文
168-183
2019-04-01（万方平台首次上网日期，不代表论文的发表时间）