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Turkish Journal of Biology

Abstract

Background/aim: Acute lung injury (ALI) is a major cause of morbidity and mortality after lung ischemia-reperfusion injury (LIRI). In recent years, pulmonary ferroptosis and its associated fibrosis have been recognized as important causes of LIRI. The purpose of this study is to investigate apigenin (APG) as a potential therapeutic target for treating LIRI-induced pulmonary ferroptosis and fibrosis.

Materials and methods: A rat model of LIRI was established and the rats were randomly divided into three groups, a sham group, a LIRI group, and an APG group. The pathological changes of the lung tissue were evaluated using hematoxylin-eosin staining and Masson’s trichrome staining. Alterations in lung function were assessed using the pulmonary permeability index, myeloperoxidase, and wet-to-dry weight ratio. The pulmonary ferroptosis levels were evaluated by testing Fe2+, the ratio of reduced glutathione to oxidized glutathione disulfide, and malondialdehyde. Western blotting was performed to investigate the effect of APG on the expression of ferroptosis and fibrosis biomarkers in the lung tissues.

Results: The results show that APG pretreatment relieves LIRI-induced pulmonary pathological damage and functional abnormalities in rats. In addition, APG administration can significantly improve LIRI-induced pulmonary ferroptosis and fibrosis levels. However, using Nrf2 inhibitors to block the Nrf2/HO-1/GPX4 pathway significantly reversed these therapeutic effects.

Conclusion: These findings suggest that APG protects against LIRI-induced ferroptosis and fibrosis of lung tissues via the activation of the Nrf2/HO-1/GPX4 axis.

Author ORCID Identifier

Liang ZHANG: 0009-0003-7680-7556

Haojie LI: 0009-0005-8667-9767

Shichen XU: 0009-0002-9040-3374

Hao WEN: 0009-0005-3443-1540

Chaoxiao YU: 0009-0003-8067-0070

DOI

10.55730/1300-0152.2732

Keywords

Apigenin, lung ischemia-reperfusion injury, Nrf2/HO-1/GPX4, ferroptosis, fibrosis

First Page

138

Last Page

147

Publisher

Scientific and Technological Research Council of Türkiye (TUBITAK)

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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