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

To explore the potential mechanisms by which ferroptosis contributes to paraquat-induced acute lung injury in mice and its forensic significance.

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).

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).

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.