Role of Reactive Oxygen Species in Collagen-Induced Platelet Activation and the Protective Effects of Antioxidants

Collagen plays a crucial role in platelet activation and thrombosis, yet the underlying mechanisms involving reactive oxygen species (ROS) remain incompletely understood. This study investigated how collagen modulates ROS generation and platelet aggregation both in vitro and in vivo, as well as eval...

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Main Authors: Jin-Yi Han, Hideo Utsumi, Han-Young Chung
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Antioxidants
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Online Access:https://www.mdpi.com/2076-3921/14/4/497
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author Jin-Yi Han
Hideo Utsumi
Han-Young Chung
author_facet Jin-Yi Han
Hideo Utsumi
Han-Young Chung
author_sort Jin-Yi Han
collection DOAJ
description Collagen plays a crucial role in platelet activation and thrombosis, yet the underlying mechanisms involving reactive oxygen species (ROS) remain incompletely understood. This study investigated how collagen modulates ROS generation and platelet aggregation both in vitro and in vivo, as well as evaluating the protective effects of antioxidants. In vitro, collagen induced dose-dependent platelet aggregation and increased ROS generation, evidenced by the enhanced EMPO adduct formation detected via electron spin resonance (ESR). In vivo experiments demonstrated that collagen administration significantly accelerated CAT-1 decay, indicating elevated oxidative stress with a transient peak around 1 minute post-treatment. Furthermore, escalating collagen doses correlated with increased ROS generation and reduced survival rates in mice, underscoring collagen’s impact on oxidative stress and thrombosis severity. Importantly, treatment with enzymatic antioxidants (superoxide dismutase, catalase) and non-enzymatic antioxidants (DMTU, Tiron, mannitol) significantly attenuated collagen-induced oxidative stress and improved animal survival. Collectively, these findings elucidate the pivotal role of ROS in collagen-induced platelet activation and thrombosis and highlight antioxidants as promising therapeutic candidates for preventing thrombotic disorders and managing cardiovascular risk.
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spelling doaj-art-88e92a0ad0a94c53895b0b615caf06ea2025-08-20T03:14:16ZengMDPI AGAntioxidants2076-39212025-04-0114449710.3390/antiox14040497Role of Reactive Oxygen Species in Collagen-Induced Platelet Activation and the Protective Effects of AntioxidantsJin-Yi Han0Hideo Utsumi1Han-Young Chung2Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Keimyung University Dongsan Medical Center, 1035 Dalgubeol-daero, Dalseo-gu, Daegu 42601, Republic of KoreaFaculty of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, JapanCollege of Pharmacy, Chungnam National University, Daejeon 34134, Republic of KoreaCollagen plays a crucial role in platelet activation and thrombosis, yet the underlying mechanisms involving reactive oxygen species (ROS) remain incompletely understood. This study investigated how collagen modulates ROS generation and platelet aggregation both in vitro and in vivo, as well as evaluating the protective effects of antioxidants. In vitro, collagen induced dose-dependent platelet aggregation and increased ROS generation, evidenced by the enhanced EMPO adduct formation detected via electron spin resonance (ESR). In vivo experiments demonstrated that collagen administration significantly accelerated CAT-1 decay, indicating elevated oxidative stress with a transient peak around 1 minute post-treatment. Furthermore, escalating collagen doses correlated with increased ROS generation and reduced survival rates in mice, underscoring collagen’s impact on oxidative stress and thrombosis severity. Importantly, treatment with enzymatic antioxidants (superoxide dismutase, catalase) and non-enzymatic antioxidants (DMTU, Tiron, mannitol) significantly attenuated collagen-induced oxidative stress and improved animal survival. Collectively, these findings elucidate the pivotal role of ROS in collagen-induced platelet activation and thrombosis and highlight antioxidants as promising therapeutic candidates for preventing thrombotic disorders and managing cardiovascular risk.https://www.mdpi.com/2076-3921/14/4/497plateletcollagenin vivo ESRspin-trappingthrombosis
spellingShingle Jin-Yi Han
Hideo Utsumi
Han-Young Chung
Role of Reactive Oxygen Species in Collagen-Induced Platelet Activation and the Protective Effects of Antioxidants
Antioxidants
platelet
collagen
in vivo ESR
spin-trapping
thrombosis
title Role of Reactive Oxygen Species in Collagen-Induced Platelet Activation and the Protective Effects of Antioxidants
title_full Role of Reactive Oxygen Species in Collagen-Induced Platelet Activation and the Protective Effects of Antioxidants
title_fullStr Role of Reactive Oxygen Species in Collagen-Induced Platelet Activation and the Protective Effects of Antioxidants
title_full_unstemmed Role of Reactive Oxygen Species in Collagen-Induced Platelet Activation and the Protective Effects of Antioxidants
title_short Role of Reactive Oxygen Species in Collagen-Induced Platelet Activation and the Protective Effects of Antioxidants
title_sort role of reactive oxygen species in collagen induced platelet activation and the protective effects of antioxidants
topic platelet
collagen
in vivo ESR
spin-trapping
thrombosis
url https://www.mdpi.com/2076-3921/14/4/497
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AT hideoutsumi roleofreactiveoxygenspeciesincollageninducedplateletactivationandtheprotectiveeffectsofantioxidants
AT hanyoungchung roleofreactiveoxygenspeciesincollageninducedplateletactivationandtheprotectiveeffectsofantioxidants