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Nutrients
Volume 14
Issue 21
10.3390/nu14214599
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Article

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

by
Yang Li
1,2,†,
Miao Sun
1,2,†,
Fuyang Cao
1,3,
Yu Chen
3,
Linlin Zhang
4,
Hao Li
2,
Jiangbei Cao
2,
Jie Song
5,
Yulong Ma
2,
Weidong Mi
2,* and
Xiaoying Zhang
2,*
1
Chinese PLA Medical School, Beijing 100853, China
2
Department of Anesthesiology, First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
3
Department of Anesthesiology, Sixth Medical Center of Chinese PLA General Hospital, Beijing 100048, China
4
Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin 300052, China
5
Nursing Department, First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Nutrients 2022, 14(21), 4599; https://doi.org/10.3390/nu14214599
Submission received: 27 August 2022 / Revised: 25 October 2022 / Accepted: 28 October 2022 / Published: 1 November 2022
(This article belongs to the Special Issue Ironing Human Health: From Basic Discovery to Clinical Translational Medicine)
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Abstract

CNS inflammation is known to be an important pathogenetic mechanism of perioperative neurocognitive disorder (PND), and iron overload was reported to participate in this process accompanied by oxidative stress. Ferroptosis is an iron-dependent form of cell death, and occurs in multiple neurodegenerative diseases with cognitive disorder. However, the effect of ferroptosis in inflammation-related PND is unknown. In this study, we found that the ferroptosis inhibitor liproxstatin-1 ameliorated memory deficits in the mouse model of lipopolysaccharide (LPS)-induced cognitive impairment. Moreover, liproxstatin-1 decreased the activation of microglia and the release of interleukin (IL)-6 and tumor necrosis factor-alpha (TNF)-α, attenuated oxidative stress and lipid peroxidation, and further weakened mitochondrial injury and neuronal damage after LPS exposure. Additionally, the protective effect of liproxstatin-1 was related to the alleviation of iron deposition and the regulation of the ferroptosis-related protein family TF, xCT, Fth, Gpx4, and FtMt. These findings enhance our understanding of inflammation-involved cognitive dysfunction and shed light on future preclinical studies.
Keywords: ferroptosis; iron; neuroinflammation; memory impairment; oxidative stress ferroptosis; iron; neuroinflammation; memory impairment; oxidative stress

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MDPI and ACS Style

Li, Y.; Sun, M.; Cao, F.; Chen, Y.; Zhang, L.; Li, H.; Cao, J.; Song, J.; Ma, Y.; Mi, W.; et al. The Ferroptosis Inhibitor Liproxstatin-1 Ameliorates LPS-Induced Cognitive Impairment in Mice. Nutrients 2022, 14, 4599. https://doi.org/10.3390/nu14214599

AMA Style

Li Y, Sun M, Cao F, Chen Y, Zhang L, Li H, Cao J, Song J, Ma Y, Mi W, et al. The Ferroptosis Inhibitor Liproxstatin-1 Ameliorates LPS-Induced Cognitive Impairment in Mice. Nutrients. 2022; 14(21):4599. https://doi.org/10.3390/nu14214599

Chicago/Turabian Style

Li, Yang, Miao Sun, Fuyang Cao, Yu Chen, Linlin Zhang, Hao Li, Jiangbei Cao, Jie Song, Yulong Ma, Weidong Mi, and et al. 2022. "The Ferroptosis Inhibitor Liproxstatin-1 Ameliorates LPS-Induced Cognitive Impairment in Mice" Nutrients 14, no. 21: 4599. https://doi.org/10.3390/nu14214599

APA Style

Li, Y., Sun, M., Cao, F., Chen, Y., Zhang, L., Li, H., Cao, J., Song, J., Ma, Y., Mi, W., & Zhang, X. (2022). The Ferroptosis Inhibitor Liproxstatin-1 Ameliorates LPS-Induced Cognitive Impairment in Mice. Nutrients, 14(21), 4599. https://doi.org/10.3390/nu14214599

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