Cargando…

Combination of Colchicine and Ticagrelor Inhibits Carrageenan-Induced Thrombi in Mice

The formation of a thrombus is closely related to oxidative stress and inflammation. Colchicine is one of the most commonly prescribed medication for gout treatment, with anti-inflammation and antioxidative stress properties. Therefore, we speculated that it is possible for colchicine to treat throm...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhang, BuChun, Huang, Rong, Yang, DaiGang, Chen, GuiLan, Chen, YuanLi, Han, Jihong, Zhang, Shuang, Ma, LiKun, Yang, XiaoXiao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8786461/
https://www.ncbi.nlm.nih.gov/pubmed/35082966
http://dx.doi.org/10.1155/2022/3087198
_version_ 1784639114282270720
author Zhang, BuChun
Huang, Rong
Yang, DaiGang
Chen, GuiLan
Chen, YuanLi
Han, Jihong
Zhang, Shuang
Ma, LiKun
Yang, XiaoXiao
author_facet Zhang, BuChun
Huang, Rong
Yang, DaiGang
Chen, GuiLan
Chen, YuanLi
Han, Jihong
Zhang, Shuang
Ma, LiKun
Yang, XiaoXiao
author_sort Zhang, BuChun
collection PubMed
description The formation of a thrombus is closely related to oxidative stress and inflammation. Colchicine is one of the most commonly prescribed medication for gout treatment, with anti-inflammation and antioxidative stress properties. Therefore, we speculated that it is possible for colchicine to treat thrombosis. In this study, we used carrageenan to induce thrombosis in BALB/c mice and fed mice with colchicine, ticagrelor, and their combination, respectively. We found colchicine inhibited carrageenan-induced thrombi in mouse tail, and the inhibition was enhanced by ticagrelor. In vitro, colchicine inhibited thrombin-induced retraction of human platelet clots. Mechanically, colchicine inhibited platelet activation by reducing the expression of platelet receptors, protease-activated receptor 4 (PAR4) and CD36, and inactivating of AKT and ERK1/2 pathways. Furthermore, in human umbilical vein endothelial cells (HUVECs), colchicine showed antioxidative stress effects through increasing protein expression of glutathione peroxidase-1 (GPx-1), and mRNA levels of forkhead box O3 (FOXO3a) and superoxide dismutase 2 (SOD2). In RAW264.7 cells, colchicine reduced LPS-enhanced inflammatory response through attenuating toll-like receptor 4 (TLR4) activation. In addition, colchicine reduced LPS or ox-LDL-induced monocyte adhesion to HUVECs by inhibiting intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1) levels. Taken together, our study demonstrates that colchicine exerts antithrombotic function by attenuating platelet activation and inhibiting oxidative stress and inflammation. We also provide a potential new strategy for clinical treatment.
format Online
Article
Text
id pubmed-8786461
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Hindawi
record_format MEDLINE/PubMed
spelling pubmed-87864612022-01-25 Combination of Colchicine and Ticagrelor Inhibits Carrageenan-Induced Thrombi in Mice Zhang, BuChun Huang, Rong Yang, DaiGang Chen, GuiLan Chen, YuanLi Han, Jihong Zhang, Shuang Ma, LiKun Yang, XiaoXiao Oxid Med Cell Longev Research Article The formation of a thrombus is closely related to oxidative stress and inflammation. Colchicine is one of the most commonly prescribed medication for gout treatment, with anti-inflammation and antioxidative stress properties. Therefore, we speculated that it is possible for colchicine to treat thrombosis. In this study, we used carrageenan to induce thrombosis in BALB/c mice and fed mice with colchicine, ticagrelor, and their combination, respectively. We found colchicine inhibited carrageenan-induced thrombi in mouse tail, and the inhibition was enhanced by ticagrelor. In vitro, colchicine inhibited thrombin-induced retraction of human platelet clots. Mechanically, colchicine inhibited platelet activation by reducing the expression of platelet receptors, protease-activated receptor 4 (PAR4) and CD36, and inactivating of AKT and ERK1/2 pathways. Furthermore, in human umbilical vein endothelial cells (HUVECs), colchicine showed antioxidative stress effects through increasing protein expression of glutathione peroxidase-1 (GPx-1), and mRNA levels of forkhead box O3 (FOXO3a) and superoxide dismutase 2 (SOD2). In RAW264.7 cells, colchicine reduced LPS-enhanced inflammatory response through attenuating toll-like receptor 4 (TLR4) activation. In addition, colchicine reduced LPS or ox-LDL-induced monocyte adhesion to HUVECs by inhibiting intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1) levels. Taken together, our study demonstrates that colchicine exerts antithrombotic function by attenuating platelet activation and inhibiting oxidative stress and inflammation. We also provide a potential new strategy for clinical treatment. Hindawi 2022-01-17 /pmc/articles/PMC8786461/ /pubmed/35082966 http://dx.doi.org/10.1155/2022/3087198 Text en Copyright © 2022 BuChun Zhang et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Zhang, BuChun
Huang, Rong
Yang, DaiGang
Chen, GuiLan
Chen, YuanLi
Han, Jihong
Zhang, Shuang
Ma, LiKun
Yang, XiaoXiao
Combination of Colchicine and Ticagrelor Inhibits Carrageenan-Induced Thrombi in Mice
title Combination of Colchicine and Ticagrelor Inhibits Carrageenan-Induced Thrombi in Mice
title_full Combination of Colchicine and Ticagrelor Inhibits Carrageenan-Induced Thrombi in Mice
title_fullStr Combination of Colchicine and Ticagrelor Inhibits Carrageenan-Induced Thrombi in Mice
title_full_unstemmed Combination of Colchicine and Ticagrelor Inhibits Carrageenan-Induced Thrombi in Mice
title_short Combination of Colchicine and Ticagrelor Inhibits Carrageenan-Induced Thrombi in Mice
title_sort combination of colchicine and ticagrelor inhibits carrageenan-induced thrombi in mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8786461/
https://www.ncbi.nlm.nih.gov/pubmed/35082966
http://dx.doi.org/10.1155/2022/3087198
work_keys_str_mv AT zhangbuchun combinationofcolchicineandticagrelorinhibitscarrageenaninducedthrombiinmice
AT huangrong combinationofcolchicineandticagrelorinhibitscarrageenaninducedthrombiinmice
AT yangdaigang combinationofcolchicineandticagrelorinhibitscarrageenaninducedthrombiinmice
AT chenguilan combinationofcolchicineandticagrelorinhibitscarrageenaninducedthrombiinmice
AT chenyuanli combinationofcolchicineandticagrelorinhibitscarrageenaninducedthrombiinmice
AT hanjihong combinationofcolchicineandticagrelorinhibitscarrageenaninducedthrombiinmice
AT zhangshuang combinationofcolchicineandticagrelorinhibitscarrageenaninducedthrombiinmice
AT malikun combinationofcolchicineandticagrelorinhibitscarrageenaninducedthrombiinmice
AT yangxiaoxiao combinationofcolchicineandticagrelorinhibitscarrageenaninducedthrombiinmice