The Toxicology of Native Fucosylated Glycosaminoglycans and the Safety of Their Depolymerized Products as Anticoagulants

doi:10.3390/md19090487

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	The Toxicology of Native Fucosylated Glycosaminoglycans and the Safety of Their Depolymerized Products as Anticoagulants
	Lin,Lisha ; Li,Sujuan ; Gao,Na ; Wang,Weili ; Zhang,Taocui ; Yang,Lian ; Yang,Xingzhi ; Luo,Dan ; Ji,Xu; Zhao,Jinhua
	2021
发表期刊	MARINE DRUGS
ISSN	1660-3397
卷号	19 期号:9 页码:487
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.
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
WOS记录号	WOS:000700285100001
引用统计
文献类型	期刊论文
条目标识符	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.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Yunnan, Peoples R China 2.Univ Chinese Acad Sci, Coll Life Sci, Beijing 100049, Peoples R China 3.South Cent Univ Natl, Sch Pharmaceut Sci, Wuhan 430074, Peoples R China 4.Yunnan Univ Chinese Med, Coll Tradit Chinese Med, Kunming 650201, Yunnan, 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.

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