The Ferroptosis Inhibitor Liproxstatin-1 Ameliorates LPS-Induced Cognitive Impairment in Mice

Yang, Li; Sun, Miao; Cao, Fuyang; Chen, Yu; Zhang, Linlin; Li, Hao; Cao, Jiangbei; Song, Jie‐Young; Ma, Yulong; Mi, Weidong; Zhang, Xiaoying

doi:10.3390/nu14214599

Cited by 23 publications

(14 citation statements)

References 94 publications

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“…Inhibition of GPX4 activity leads to the accumulation of lipid peroxides, which is an indicator of ferroptosis in cells. Our investigation found that administering DM significantly elevated GPX4 expression levels in mice with VAP ( 31 , 32 ).…”

Section: Discussionmentioning

confidence: 53%

RETRACTED: Macrophages depletion alleviates lung injury by modulating AKT3/GXP4 following ventilator associated pneumonia

Zhu,

Chen,

Xie

et al. 2023

Front. Immunol.

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BackgroundAKT3 appears to play a role in lung cancer. However, its role in ventilator-associated pneumonia is still unclear. Therefore, this study aimed to investigate the role of AKT3 in macrophages during ventilator-associated pneumonia.MethodsThe mRNA level of AKT3, Data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), The data is analyzed using the Xiantao academic analysis tool. Additionally, the roles of AKT3 in ventilator-associated pneumonia (VAP) were investigated through in vivo experiments.ResultsAKT3 was differentially expressed in various normal and tumor tissues. Functional enrichment analysis indicated the immunomodulatory function and inflammatory response of AKT3 in lung cancer. Depletion of macrophages protected against lung epithelial cells and significantly decreased MMP9, MMP19, FTH, and FTL expression levels and increased GPX4 expression levels, while partially reversing the changes in macrophage. Mechanistically, macrophage depletion attenuates ferroptosis of lung epithelial cells by modulating AKT3 following VAP.ConclusionCollectively, this study suggests the need for further validation of the immunoregulatory function of AKT3 in lung cancer. Additionally, macrophage depletion mitigates lung injury by modulating the AKT3/GPX4 pathway in the context of VAP.

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Section: Discussionmentioning

confidence: 53%

RETRACTED: Macrophages depletion alleviates lung injury by modulating AKT3/GXP4 following ventilator associated pneumonia

Zhu,

Chen,

Xie

et al. 2023

Front. Immunol.

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“…Due to the critical role of lipid peroxidation in ferroptosis, Liproxstatin‐1, which is one of the most investigated lipid peroxidation inhibitors, was used in this study. Our study represents one of the first studies utilizing Liproxstatin‐1 for treatment of cognitive impairment (Li, Sun et al., 2022), particularly in the case of sevoflurane‐induced cognitive disorder. In line with our findings, previous studies have also reported the neuroprotective effects of ferroptosis inhibitors in models of neurodegeneration and brain injury.…”

Section: Discussionmentioning

confidence: 99%

“…Cognitive deficits following anesthesia are notably prevalent among older surgical patients, an issue known as postoperative cognitive dysfunction (POCD). Approximately 25% of patients over 60 exhibit signs of POCD at 1 week postsurgery, with symptoms enduring beyond three months in 10% of cases (Li, Sun et al., 2022). Given the significance of these findings, our research has specifically concentrated on the geriatric population.…”

Section: Discussionmentioning

confidence: 99%

Liproxstatin‐1 alleviates ferroptosis in sevoflurane anesthesia‐induced cognitive deficits of aged mice: The role oxidative stress

Li,

Chen,

Wang

et al. 2024

Synapse

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In this study, we aimed to validate the hypothesis that the interplay between sevoflurane, oxidative stress and ferroptosis is crucial for the pathogenesis of sevoflurane‐induced cognitive impairment in aged individuals. The mice with sevoflurane‐induced cognitive impairment were used to explore the effects of sevoflurane on oxidative stress, iron homeostasis, and cognitive function in aged mice. Iron content and oxidative stress markers were analyzed in hippocampal tissue homogenates using specific assays. Additionally, the levels of iron death‐related markers (Fth1 and Gpx4) were assessed by real‐time PCR and Western blotting. Morris Water Maze and novel object recognition (NOR) tests were conducted to evaluate cognitive function. Sevoflurane exposure in aged mice resulted in a significant increase in iron overloading in the hippocampus, followed by a subsequent stabilization. Oxidative stress levels were elevated in the hippocampal tissue of sevoflurane‐exposed mice, and a significant correlation was observed between iron death and oxidative stress. Liproxstatin‐1, a ferroptosis inhibitor, effectively ameliorated the decline in memory and learning abilities induced by sevoflurane anesthesia. Liproxstatin‐1 treatment reduced iron overload and oxidative stress in the hippocampal tissue of aged mice. The expression of Fth1 and Gpx4, iron death‐related markers, was downregulated following Liproxstatin‐1 intervention. Our findings suggest that sevoflurane anesthesia disrupts iron homeostasis, leading to increased oxidative stress and cognitive impairment in aged mice. These results highlight the potential of targeting iron‐mediated processes to mitigate sevoflurane‐induced cognitive impairment in the aging population.

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“…In addition, mind bomb-2 (MIB2) and ferroptosis inhibitor liproxstatin-1 may regulate iron death-related pathways and oxidative stress in the hippocampus, which in turn may repair perioperative BBB damage ( Zhao et al, 2021 ; Li et al, 2022 ). Ferroptosis may be involved in the pathophysiological processes of AD.…”

Section: Potential Adverse Effects Caused By Bbb Damagementioning

confidence: 99%

Research progress on perioperative blood-brain barrier damage and its potential mechanism

Qiu

et al. 2023

Front. Cell Dev. Biol.

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The blood-brain barrier (BBB) is an important barrier separating the central nervous system from the periphery. The composition includes endothelial cells, pericytes, astrocytes, synapses and tight junction proteins. During the perioperative period, anesthesia and surgical operations are also a kind of stress to the body, which may be accompanied by blood-brain barrier damage and brain metabolism dysfunction. Perioperative blood-brain barrier destruction is closely associated with cognitive impairment and may increase the risk of postoperative mortality, which is not conducive to enhanced recovery after surgery. However, the potential pathophysiological process and specific mechanism of blood-brain barrier damage during the perioperative period have not been fully elucidated. Changes in blood-brain barrier permeability, inflammation and neuroinflammation, oxidative stress, ferroptosis, and intestinal dysbiosis may be involved in blood-brain barrier damage. We aim to review the research progress of perioperative blood-brain barrier damage and its potential adverse effects and potential molecular mechanisms, and provide ideas for the study of homeostasis maintenance of brain function and precision anesthesia.

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The Ferroptosis Inhibitor Liproxstatin-1 Ameliorates LPS-Induced Cognitive Impairment in Mice

Cited by 23 publications

References 94 publications

RETRACTED: Macrophages depletion alleviates lung injury by modulating AKT3/GXP4 following ventilator associated pneumonia

RETRACTED: Macrophages depletion alleviates lung injury by modulating AKT3/GXP4 following ventilator associated pneumonia

Liproxstatin‐1 alleviates ferroptosis in sevoflurane anesthesia‐induced cognitive deficits of aged mice: The role oxidative stress

Research progress on perioperative blood-brain barrier damage and its potential mechanism

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