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Quercetin alleviates PM2.5-induced chronic lung injury in mice by targeting ferroptosis
Shibin Ding1, Jinjin Jiang1, Yang Li1
1Public Health and Management, Jiangsu Vocational College of Medicine, Yancheng, Jiangsu, China.
Background:
PM2.5 is a well-known harmful air pollutant that can lead to acute exacerbation and aggravation of respiratory diseases. Although ferroptosis is involves in the pathological process of pulmonary disease, the potential mechanism of ferroptosis in PM2.5-caused lung inflammation and fibrosis need to be further clarified. Quercetin is a phenolic compound that can inhibit ferroptosis in various diseases. Hence, this study explores the role of ferroptosis in lung injury induced by PM2.5 in order to further elucidate the beneficial effect of quercetin and its underlying mechanism.
Methods:
C57BL/6J mice were treated with either saline or PM2.5 by intratracheal instillation 20 times (once every two days). Additionally, PM2.5-treated mice were supplemented with two doses of quercetin. Lung injury, lipid peroxidation, iron content and ferroptosis marker protein expression and the Nrf2 signaling pathway were evaluated. In vitro, cell experiments were applied to verify the mechanisms underlying the links between Nrf2 signaling pathway activation and ferroptosis as well as between ferroptosis and inflammation.
Results:
In vivo, PM2.5 increased lung inflammation and caused lung fibrosis and increased lipid peroxidation contents, iron contents and ferroptosis markers in lung tissues; these effects were significantly reversed by quercetin. Additionally, quercetin upregulated the nuclear Nrf2 expression and downregulated Keap1 expression in lung tissues of PM2.5-exposed mice. Quercetin decreased lipid peroxidation products, iron contents and ferroptosis levels and increased the nuclear translocation of Nrf2 and the degradation of Keap1 in PM2.5-exposed BEAS-2B cells. Moreover, we found that quercetin and dimethyl fumarate markedly decreased lipid peroxidation production and ferroptosis by activating the Nrf2-Keap1 pathway in PM2.5-exposed cells. Furthermore, quercetin reduced inflammatory cytokines and TGF-β1 in PM2.5-exposed cells.
Conclusion:
Our data suggested that Nrf2 is involved in ferroptosis in PM2.5-induced lung injury, and quercetin can alleviate these adverse effects via activating Nrf2-Keap1 signaling pathway.
Insights
Quercetin alleviates lung injury from fine particulate matter (PM2.5) by inhibiting ferroptosis through the Nrf2-Keap1 pathway. This study clarifies the mechanism of PM2.5-induced lung damage and quercetin
Area of Science:
- Environmental Health
- Toxicology
- Cell Biology
Background:
- Particulate matter (PM2.5) exposure exacerbates respiratory diseases.
- Ferroptosis plays a role in pulmonary disease pathogenesis.
- The precise mechanisms of PM2.5-induced ferroptosis in lung injury require further investigation.
Purpose of the Study:
- To explore the role of ferroptosis in PM2.5-induced lung injury.
- To elucidate the protective effects and underlying mechanisms of quercetin against PM2.5-induced lung damage.
Main Methods:
- Mice were exposed to PM2.5 and treated with quercetin.
- Lung injury, oxidative stress markers, iron levels, and ferroptosis indicators were assessed.
- In vitro cell models were used to confirm the Nrf2 signaling pathway's role in ferroptosis and inflammation.
Main Results:
- PM2.5 exposure induced lung inflammation, fibrosis, and ferroptosis, which were ameliorated by quercetin.
- Quercetin upregulated Nrf2 and downregulated Keap1 expression in lung tissue and cells.
- Quercetin and dimethyl fumarate reduced ferroptosis by activating the Nrf2-Keap1 pathway and decreased inflammatory cytokines.
Conclusions:
- Nrf2 is implicated in ferroptosis during PM2.5-induced lung injury.
- Quercetin exerts protective effects by activating the Nrf2-Keap1 signaling pathway, mitigating ferroptosis and inflammation.
