Alpha-linolenic acid protects against heatstroke-induced acute lung injury by inhibiting ferroptosis through Nrf2 activation.

IF 7.4 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Redox Report Pub Date : 2025-12-01 Epub Date: 2025-07-27 DOI:10.1080/13510002.2025.2538294

Lin Wang, Jiamin Ma, Zhaozheng Li, Xinru Zhao, Ying Chen, Pei Wang, Yi Li, Yuwei Chen, Xuanqi Yao, Liangfang Yao, Jinbao Li

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Abstract

Heatstroke (HS)-induced acute lung injury (ALI) has high morbidity and mortality with no specific therapies. Ferroptosis, a form of programmed cell death driven by lipid peroxidation due to reduced Glutathione Peroxidase 4 (GPX4) activity, is closely linked to HS-induced ALI. This study investigated the effect of alpha-linolenic acid (ALA), a plant-derived ω-3 fatty acid, on ferroptosis in a mouse model of HS-induced ALI. Histopathology analysis found that ALA can attenuate lung injury and improve the 7-day survival rate in mice with HS-induced ALI. In addition, ALA significantly reduced the levels of reactive oxygen species (ROS) and malondialdehyde (MDA), while increasing the level of antioxidant glutathione (GSH). Further analysis showed that ALA upregulated the levels of SLC7A11 and GPX4 by promoting the nuclear translocation of Nrf2. This led to increased GSH synthesis but reduced ROS accumulation, which in turn suppressed ferroptosis and protected the mice against HS-induced ALI. Additionally, the protective effect of ALA was found to be diminished in Nrf2-deficient mice. In summary, ALA inhibits ferroptosis in macrophages by activating the Nrf2/SLC7A11/GPX4 pathway and attenuates HS-induced ALI.

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α -亚麻酸可通过Nrf2激活抑制铁下垂，从而预防中暑引起的急性肺损伤。

中暑（HS）引起的急性肺损伤（ALI）发病率和死亡率高，无特异性治疗方法。Ferroptosis是一种程序性细胞死亡形式，由谷胱甘肽过氧化物酶4 （GPX4）活性降低引起的脂质过氧化引起，与hs诱导的ALI密切相关。本研究探讨了α -亚麻酸（α -亚麻酸，一种植物源性ω-3脂肪酸）对hs诱导ALI小鼠模型铁下垂的影响。组织病理学分析发现，ALA可减轻hs诱导ALI小鼠的肺损伤，提高其7天存活率。此外，ALA显著降低了活性氧（ROS）和丙二醛（MDA）水平，同时增加了抗氧化剂谷胱甘肽（GSH）水平。进一步分析表明，ALA通过促进Nrf2的核易位而上调SLC7A11和GPX4的水平。这导致GSH合成增加，但ROS积累减少，从而抑制铁下垂并保护小鼠免受hs诱导的ALI。此外，在nrf2缺陷小鼠中发现ALA的保护作用减弱。综上所述，ALA通过激活Nrf2/SLC7A11/GPX4通路抑制巨噬细胞铁凋亡，减轻hs诱导的ALI。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Redox Report 生物-生化与分子生物学

CiteScore

6.10

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： Redox Report is a multidisciplinary peer-reviewed open access journal focusing on the role of free radicals, oxidative stress, activated oxygen, perioxidative and redox processes, primarily in the human environment and human pathology. Relevant papers on the animal and plant environment, biology and pathology will also be included. While emphasis is placed upon methodological and intellectual advances underpinned by new data, the journal offers scope for review, hypotheses, critiques and other forms of discussion.