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

Overview

Journal Nutrients

Date 2022 Nov 11

PMID 36364859

Authors

Yang Li

Miao Sun

Fuyang Cao

Yu Chen

Linlin Zhang

Hao Li

Jiangbei Cao

Jie Song

Yulong Ma

Weidong Mi

Xiaoying Zhang

Affiliations

Soon will be listed here.

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.

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