Role of Ferroptosis in Paraquat-Induced Acute Lung Injury in Mice

doi:10.12116/j.issn.1004-5619.2024.440115

Abstract

Abstract:

Objective To explore the potential mechanisms by which ferroptosis contributes to paraquat-induced acute lung injury in mice and its forensic significance. Methods Sixty healthy male clean-grade Kunming mice aged 6-8 weeks were randomly divided into a control group and paraquat exposure groups （1 d, 3 d, 5 d, 7 d and 14 d）, with 10 mice per group. The exposure groups were given a single intraperitoneal injection of 20 mg/kg paraquat solution, while the control group was given an equal volume of 0.9% saline. General conditions after exposure were observed. Hematoxylin-eosin （HE） staining was used to examine pathological changes in lung tissues, and Prussian blue staining was used to detect iron content. Oxidative stress indicators, such as reduced glutathione （GSH） and malondialdehyde （MDA）, were measured by relevant testing kits. Immunohistochemistry and Western blot were employed to detect the expression levels of ferroptosis-related proteins including glutathione peroxidase 4 （GPX4）, solute carrier family 7 member 11（SLC7A11）, and heme oxygenase-1 （HO-1）. Results With the increase of exposure time, mice in the exposure groups showed progressively aggravated fibrosis and increased iron deposition in lung tissues. GSH levels gradually decreased, while MDA levels increased significantly in the 7 d and 14 d groups. The expression of GPX4 in lung tissue decreased. The expression of SLC7A11 decreased over time, except for the 1 d group. The expression of HO-1 increased with the increase of exposure time, except for the 1 d group, and the highest expression was observed in the 7 d group. The differences between the exposure groups and the control group were statistically significant （P<0.05）. Conclusion Ferroptosis is involved in acute lung injury induced by paraquat poisoning, and research on the mechanism of ferroptosis and the temporal changes of its biomarkers may provide valuable insights for the forensic identification of paraquat poisoning.

Key words: forensic pathology, forensic toxicology, paraquat, acute lung injury, ferroptosis, mice

CLC Number:

Hao-jie QIN, Chen MO, Hong-wei LI, Zhi-jiang LIU, Zhe ZHENG. Role of Ferroptosis in Paraquat-Induced Acute Lung Injury in Mice[J]. Journal of Forensic Medicine, 2025, 41(5): 494-501.

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URL: http://www.fyxzz.cn/EN/10.12116/j.issn.1004-5619.2024.440115

http://www.fyxzz.cn/EN/Y2025/V41/I5/494

Figures/Tables 8

Fig. 1 Pathological changes of mice lung tissues at different time points after paraquat poisoning

Fig. 2 Iron staining results of mice lung tissues at different time points after paraquat poisoning

Tab. 1 The GSH and MDA contents in mice lung tissues

组别	GSH/（μg·g^-1）	MDA/（nmoL·g^-1）
对照	712.6±5.0	45.9±5.0
染毒1 d	650.8±6.0 ^1）	50.4±4.2
染毒3 d	615.9±4.8 ^1）2）	51.1±3.3
染毒5 d	560.5±13.3 ^1）2）	49.7±3.5
染毒7 d	521.1±2.7 ^1）2）	61.2±9.1 ^1）
染毒14 d	460.6±5.3 ^1）2）	76.3±11.9 ^1）

Fig. 3 Immunohistochemical staining results of GPX4 in mice lung tissues at different time points after paraquat poisoning

Fig. 4 Immunohistochemical staining results of SLC7A11 in mice lung tissues at different time points after paraquat poisoning

Fig. 5 Immunohistochemical staining results of HO-1 in mice lung tissues at different time points after paraquat poisoning

Tab. 2 Relative expression levels of GPX4， SLC7A11 and HO-1 proteins in mice lung tissues atdifferent time points after paraquat poisoning

组别	GPX4	SLC7A11	HO-1
对照	1	1	1
染毒1 d	0.58±0.09 ^1）	0.84±0.06	1.31±0.06
染毒3 d	0.46±0.07 ^1）2）	0.66±0.06 ^1）	1.40±0.11 ^1）
染毒5 d	0.34±0.08 ^1）2）	0.64±0.14 ^1）	1.55±0.06 ^1）2）
染毒7 d	0.35±0.11 ^1）2）	0.62±0.07 ^1）2）	1.79±0.10 ^1）2）
染毒14 d	0.32±0.07 ^1）2）	0.58±0.05 ^1）2）	1.52±0.06 ^1）2）

Fig. 6 Changes of GPX4， SLC7A11 and HO-1 protein expression in mice lung tissue at different time points after paraquat poisoning

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