Magnesium hydride attenuates intestinal barrier injury during hemorrhage shock by regulating neutrophil extracellular trap formation via the ROS/MAPK/PAD4 pathway
Copyright © 2024 Elsevier B.V. All rights reserved..
Magnesium hydride (MgH2) is a hydrogen storage material that is known for its high capacity and safety and is capable of releasing hydrogen in a controlled manner when administered orally. This release of hydrogen has been associated with a range of biological effects, including anti-inflammatory properties, antioxidant activity, and protection of the intestinal barrier. Previous research has shown that neutrophil extracellular traps (NETs) play a role in the dysfunction of the intestinal barrier in conditions such as sepsis and critical illnesses. However, it remains unclear as to whether MgH2 can protect the intestinal barrier by inhibiting NET formation, and the underlying mechanisms have yet to be elucidated. A rat model of hemorrhagic shock was created, and pretreatment or posttreatment procedures with MgH2 were performed. After 24 h, samples from the small intestine and blood were collected for analysis. In vitro, human neutrophils were incubated with either phorbol-12-myristate-13-acetate (PMA) or MgH2. Reactive oxygen species generation and the expression of key proteins were assessed. The results demonstrated that MgH2 administration led to a decrease in inflammatory cytokines in the serum and mitigated distant organ dysfunction in rats with HS. Furthermore, MgH2 treatment reversed histopathological damage in the intestines, improved intestinal permeability, and enhanced the expression of tight junction proteins (TJPs) during HS. Additionally, MgH2 treatment was found to suppress NET formation in the intestines. In vitro pretreatment with MgH2 alleviated intestinal monolayer barrier disruption that was induced by NETs. Mechanistically, MgH2 pretreatment reduced ROS production and NET formation, inhibited the activation of ERK and p38, and suppressed the expression of the PAD4 protein. These findings indicated that MgH2 may inhibit NET formation in a ROS/MAPK/PAD4-dependent manner, which reduces NET-related intestinal barrier damage, thus offering a novel protective role in preventing intestinal barrier dysfunction during HS.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:130 |
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| Enthalten in: |
International immunopharmacology - 130(2024) vom: 30. März, Seite 111688 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Cao, Changkui [VerfasserIn] |
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| Links: |
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| Themen: |
7YNJ3PO35Z |
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| Anmerkungen: |
Date Completed 25.03.2024 Date Revised 25.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.intimp.2024.111688 |
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| Förderinstitution / Projekttitel: |
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NLM368848698 |
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| 520 | |a Magnesium hydride (MgH2) is a hydrogen storage material that is known for its high capacity and safety and is capable of releasing hydrogen in a controlled manner when administered orally. This release of hydrogen has been associated with a range of biological effects, including anti-inflammatory properties, antioxidant activity, and protection of the intestinal barrier. Previous research has shown that neutrophil extracellular traps (NETs) play a role in the dysfunction of the intestinal barrier in conditions such as sepsis and critical illnesses. However, it remains unclear as to whether MgH2 can protect the intestinal barrier by inhibiting NET formation, and the underlying mechanisms have yet to be elucidated. A rat model of hemorrhagic shock was created, and pretreatment or posttreatment procedures with MgH2 were performed. After 24 h, samples from the small intestine and blood were collected for analysis. In vitro, human neutrophils were incubated with either phorbol-12-myristate-13-acetate (PMA) or MgH2. Reactive oxygen species generation and the expression of key proteins were assessed. The results demonstrated that MgH2 administration led to a decrease in inflammatory cytokines in the serum and mitigated distant organ dysfunction in rats with HS. Furthermore, MgH2 treatment reversed histopathological damage in the intestines, improved intestinal permeability, and enhanced the expression of tight junction proteins (TJPs) during HS. Additionally, MgH2 treatment was found to suppress NET formation in the intestines. In vitro pretreatment with MgH2 alleviated intestinal monolayer barrier disruption that was induced by NETs. Mechanistically, MgH2 pretreatment reduced ROS production and NET formation, inhibited the activation of ERK and p38, and suppressed the expression of the PAD4 protein. These findings indicated that MgH2 may inhibit NET formation in a ROS/MAPK/PAD4-dependent manner, which reduces NET-related intestinal barrier damage, thus offering a novel protective role in preventing intestinal barrier dysfunction during HS | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Gut barrier | |
| 650 | 4 | |a Hemorrhage shock | |
| 650 | 4 | |a Magnesium hydride | |
| 650 | 4 | |a Neutrophil extracellular traps | |
| 650 | 4 | |a Reactive oxygen species | |
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| 700 | 1 | |a Yu, Pan |e verfasserin |4 aut | |
| 700 | 1 | |a Chu, Chengnan |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Zhenjie |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Weiqi |e verfasserin |4 aut | |
| 700 | 1 | |a Cheng, Feng |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Heng |e verfasserin |4 aut | |
| 700 | 1 | |a Qiu, Zhaolei |e verfasserin |4 aut | |
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