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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
Source PublicationMARINE DRUGS
ISSN1660-3397
Volume19Issue:9Pages:487
AbstractFucosylated 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.
Keywordfucosylated glycosaminoglycan anticoagulant platelet aggregation contact activation hypotension pulmonary embolism CHONDROITIN SULFATE CONTACT SYSTEM COMPLEMENT COAGULATION ACTIVATION ACCUMULATION INVOLVEMENT DERIVATIVES KALLIKREIN THROMBOSIS
DOI10.3390/md19090487
WOS IDWOS:000700285100001
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Document Type期刊论文
Identifierhttp://ir.kib.ac.cn/handle/151853/73026
Collection中国科学院昆明植物研究所
Affiliation1.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
Recommended Citation
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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