The Toxicology of Native Fucosylated Glycosaminoglycans and the Safety of Their Depolymerized Products as Anticoagulants
文献类型：期刊论文
| 作者 | Lin,Lisha; Li,Sujuan; Gao,Na; Wang,Weili; Zhang,Taocui; Yang,Lian; Yang,Xingzhi; Luo,Dan; Ji,Xu ; Zhao,Jinhua
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| 刊名 | MARINE DRUGS
 |
| 出版日期 | 2021 |
| 卷号 | 19期号:9页码:487 |
| ISSN号 | 1660-3397 |
| 关键词 | fucosylated glycosaminoglycan anticoagulant platelet aggregation contact activation hypotension pulmonary embolism CHONDROITIN SULFATE CONTACT SYSTEM COMPLEMENT COAGULATION ACTIVATION ACCUMULATION INVOLVEMENT DERIVATIVES KALLIKREIN THROMBOSIS |
| DOI | 10.3390/md19090487 |
| 英文摘要 | Fucosylated glycosaminoglycan (FG) from sea cucumber is a potent anticoagulant by inhibiting intrinsic coagulation tenase (iXase). However, high-molecular-weight FGs can activate platelets and plasma contact system, and induce hypotension in rats, which limits its application. Herein, we found that FG from T. ananas (TaFG) and FG from H. fuscopunctata (HfFG) at 4.0 mg/kg (i.v.) could cause significant cardiovascular and respiratory dysfunction in rats, even lethality, while their depolymerized products had no obvious side effects. After injection, native FG increased rat plasma kallikrein activity and levels of the vasoactive peptide bradykinin (BK), consistent with their contact activation activity, which was assumed to be the cause of hypotension in rats. However, the hemodynamic effects of native FG cannot be prevented by the BK receptor antagonist. Further study showed that native FG induced in vivo procoagulation, thrombocytopenia, and pulmonary embolism. Additionally, its lethal effect could be prevented by anticoagulant combined with antiplatelet drugs. In summary, the acute toxicity of native FG is mainly ascribed to pulmonary microvessel embolism due to platelet aggregation and contact activation-mediated coagulation, while depolymerized FG is a safe anticoagulant candidate by selectively targeting iXase. |
| WOS记录号 | WOS:000700285100001 |
| 源URL | [http://ir.kib.ac.cn/handle/151853/73026]  |
| 专题 | 中国科学院昆明植物研究所 |
| 作者单位 | 1.Yunnan Univ Chinese Med, Coll Tradit Chinese Med, Kunming 650201, Yunnan, Peoples R China 2.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Yunnan, Peoples R China 3.Univ Chinese Acad Sci, Coll Life Sci, Beijing 100049, Peoples R China 4.South Cent Univ Natl, Sch Pharmaceut Sci, Wuhan 430074, Peoples R China 5.Yunnan Univ, Sch Chem Sci & Technol, Kunming 650201, Yunnan, Peoples R China |
| 推荐引用方式 GB/T 7714 | Lin,Lisha,Li,Sujuan,Gao,Na,et al. The Toxicology of Native Fucosylated Glycosaminoglycans and the Safety of Their Depolymerized Products as Anticoagulants[J]. MARINE DRUGS,2021,19(9):487. |
| APA | Lin,Lisha.,Li,Sujuan.,Gao,Na.,Wang,Weili.,Zhang,Taocui.,...&Zhao,Jinhua.(2021).The Toxicology of Native Fucosylated Glycosaminoglycans and the Safety of Their Depolymerized Products as Anticoagulants.MARINE DRUGS,19(9),487. |
| MLA | Lin,Lisha,et al."The Toxicology of Native Fucosylated Glycosaminoglycans and the Safety of Their Depolymerized Products as Anticoagulants".MARINE DRUGS 19.9(2021):487. |
入库方式： OAI收割
来源：昆明植物研究所
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