The effect of modulating platelet reactive oxygen species by the addition of antioxidants to prevent clearance of cold-stored platelets

Background: It is known that the rapid clearance of cold-stored platelets is attributed to various storage lesions, including an abnormal increase in reactive oxygen species when platelets are exposed to cold temperatures. As an antioxidant, N-acetylcysteine exhibits some significant effects on scav...

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Main Authors: Rufeng Xie, Yiming Yang, Xueyu Jiang, Li Gao, Juan Sun, Jie Yang
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:Hematology, Transfusion and Cell Therapy
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Online Access:http://www.sciencedirect.com/science/article/pii/S253113792402827X
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author Rufeng Xie
Yiming Yang
Xueyu Jiang
Li Gao
Juan Sun
Jie Yang
author_facet Rufeng Xie
Yiming Yang
Xueyu Jiang
Li Gao
Juan Sun
Jie Yang
author_sort Rufeng Xie
collection DOAJ
description Background: It is known that the rapid clearance of cold-stored platelets is attributed to various storage lesions, including an abnormal increase in reactive oxygen species when platelets are exposed to cold temperatures. As an antioxidant, N-acetylcysteine exhibits some significant effects on scavenging various reactive oxygen species and inhibiting cell damage and apoptosis. Aims: This study aimed to investigate the effects of N-acetylcysteine on reducing reactive oxygen species production and protecting cold-stored platelets from phagocytosis and clearance, and to determine the optimal concentration of N-acetylcysteine. Methods: Platelet concentrates were divided into three groups: room-temperature-stored platelets, cold-stored platelets, and cold-stored platelets with the addition of different concentrations of N-acetylcysteine. After five days of storage, reactive oxygen species production, lipid peroxidation levels, activation marker expressions, GPIb/ɑ desialylation with exposure of glycan residues and other quality parameters of platelets were measured and compared between the groups. Phagocytosis of platelets was detected by phorbol 12-myristate 13-acetate-activated THP-1 or Hep G2 cells. Moreover, the recovery of infused platelets was measured in severe combined immunodeficient mice at different timepoints. Results: After 5 days of storage, cytoplasmic reactive oxygen species significantly increased in chilled compared to non-chilled platelets; they were notably reduced with the addition of N-acetylcysteine, particularly at a concentration of 5 mM. Compared with chilled platelets, the P-selectin and phosphatidylserine expressions, as well as exposure of GPIb/ɑ glycan residues, were significantly reduced with 5 mM of N-acetylcysteine. Phagocytosis of platelets by THP-1 or Hep G2 cells was significantly lower in 5 mM of N-acetylcysteine compared to cold-stored platelets without N-acetylcysteine. Conclusions: This study demonstrated correlations between reactive oxygen species production and their pro-oxidant effects on platelet clearance after cold storage. The addition of N-acetylcysteine at an appropriate concentration do not only protects chilled platelets from storage lesions caused by reactive oxygen species overproduction but also prevents platelet phagocytosis in vitro and clearance in vivo, thereby extending circulating time.
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spelling doaj-art-527fdfbd95f6453fb8bbe9c39d68153d2025-08-20T02:52:31ZengElsevierHematology, Transfusion and Cell Therapy2531-13792024-12-0146S272S28310.1016/j.htct.2024.09.2479The effect of modulating platelet reactive oxygen species by the addition of antioxidants to prevent clearance of cold-stored plateletsRufeng Xie0Yiming Yang1Xueyu Jiang2Li Gao3Juan Sun4Jie Yang5Blood Engineering Laboratory, Shanghai Blood Center, Shanghai, ChinaBlood Engineering Laboratory, Shanghai Blood Center, Shanghai, ChinaBlood Engineering Laboratory, Shanghai Blood Center, Shanghai, ChinaBlood Engineering Laboratory, Shanghai Blood Center, Shanghai, ChinaBlood Engineering Laboratory, Shanghai Blood Center, Shanghai, ChinaCorresponding author.; Blood Engineering Laboratory, Shanghai Blood Center, Shanghai, ChinaBackground: It is known that the rapid clearance of cold-stored platelets is attributed to various storage lesions, including an abnormal increase in reactive oxygen species when platelets are exposed to cold temperatures. As an antioxidant, N-acetylcysteine exhibits some significant effects on scavenging various reactive oxygen species and inhibiting cell damage and apoptosis. Aims: This study aimed to investigate the effects of N-acetylcysteine on reducing reactive oxygen species production and protecting cold-stored platelets from phagocytosis and clearance, and to determine the optimal concentration of N-acetylcysteine. Methods: Platelet concentrates were divided into three groups: room-temperature-stored platelets, cold-stored platelets, and cold-stored platelets with the addition of different concentrations of N-acetylcysteine. After five days of storage, reactive oxygen species production, lipid peroxidation levels, activation marker expressions, GPIb/ɑ desialylation with exposure of glycan residues and other quality parameters of platelets were measured and compared between the groups. Phagocytosis of platelets was detected by phorbol 12-myristate 13-acetate-activated THP-1 or Hep G2 cells. Moreover, the recovery of infused platelets was measured in severe combined immunodeficient mice at different timepoints. Results: After 5 days of storage, cytoplasmic reactive oxygen species significantly increased in chilled compared to non-chilled platelets; they were notably reduced with the addition of N-acetylcysteine, particularly at a concentration of 5 mM. Compared with chilled platelets, the P-selectin and phosphatidylserine expressions, as well as exposure of GPIb/ɑ glycan residues, were significantly reduced with 5 mM of N-acetylcysteine. Phagocytosis of platelets by THP-1 or Hep G2 cells was significantly lower in 5 mM of N-acetylcysteine compared to cold-stored platelets without N-acetylcysteine. Conclusions: This study demonstrated correlations between reactive oxygen species production and their pro-oxidant effects on platelet clearance after cold storage. The addition of N-acetylcysteine at an appropriate concentration do not only protects chilled platelets from storage lesions caused by reactive oxygen species overproduction but also prevents platelet phagocytosis in vitro and clearance in vivo, thereby extending circulating time.http://www.sciencedirect.com/science/article/pii/S253113792402827XCold-stored plateletsReactive oxygen species (ROS)N-acetylcysteine (NAC)Clearance
spellingShingle Rufeng Xie
Yiming Yang
Xueyu Jiang
Li Gao
Juan Sun
Jie Yang
The effect of modulating platelet reactive oxygen species by the addition of antioxidants to prevent clearance of cold-stored platelets
Hematology, Transfusion and Cell Therapy
Cold-stored platelets
Reactive oxygen species (ROS)
N-acetylcysteine (NAC)
Clearance
title The effect of modulating platelet reactive oxygen species by the addition of antioxidants to prevent clearance of cold-stored platelets
title_full The effect of modulating platelet reactive oxygen species by the addition of antioxidants to prevent clearance of cold-stored platelets
title_fullStr The effect of modulating platelet reactive oxygen species by the addition of antioxidants to prevent clearance of cold-stored platelets
title_full_unstemmed The effect of modulating platelet reactive oxygen species by the addition of antioxidants to prevent clearance of cold-stored platelets
title_short The effect of modulating platelet reactive oxygen species by the addition of antioxidants to prevent clearance of cold-stored platelets
title_sort effect of modulating platelet reactive oxygen species by the addition of antioxidants to prevent clearance of cold stored platelets
topic Cold-stored platelets
Reactive oxygen species (ROS)
N-acetylcysteine (NAC)
Clearance
url http://www.sciencedirect.com/science/article/pii/S253113792402827X
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