Exploring Nrf2 as a Potential Biomarker in Asthma: Links to Hypoxia, Oxidative Stress, and Ferroptosis in a Cross-Sectional Study

Yupeng Li, Xinkai Ma, Yanqing Xing, Chuanchuan Dong, Liting Feng, Rujie Huo, Fei Hu, Xinrui Tian The Second Hospital of Shanxi Medical University, Taiyuan, People’s Republic of ChinaCorrespondence: Xinrui Tian, Department of Gerontology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China, Tel +8613834575570, Email [email protected]: This study aims to explore the potential role of Nrf2 as a biomarker in asthma and its associations with hypoxia, oxidative stress, and ferroptosis-related indicators in a cross-sectional study.Patients and Methods: This study involved the collection of peripheral blood samples from participants to isolate serum and peripheral blood mononuclear cells (PBMCs). Enzyme-linked immunosorbent assay (ELISA) and other assay kits was performed to quantify the levels of Nrf2, HIF-1α, SOD, and MDA in PBMCs, alongside the activities of SOD and GSH-Px, and serum concentrations of IL-4 and IL-13. Quantitative Real-time PCR (qRT-PCR) was used to assess the expression levels of GPX4, NCOA4, SCL7A11, and HMGB1 in PBMCs. Clinical data were collected and analyzed statistically. Receiver operating characteristic (ROC) curve analysis was employed to assess the diagnostic performance of these indicators.Results: Compared with the control group, asthma patients showed significantly lower levels of Nrf2 and SOD in PBMCs, as well as reduced expression of GPX4, SCL7A11, and NCOA4 (P < 0.05). In contrast, levels of HIF-1α and MDA, as well as the expression of HMGB1, were significantly elevated in the asthma group (P < 0.05). Correlation analysis indicated that Nrf2, HIF-1α, and MDA levels in PBMCs were associated with certain clinical indicators in asthma patients. ROC curve analysis further demonstrated that these indicators exhibited a certain diagnostic performance for asthma and severe asthma. Additionally, in asthma patients, Nrf2 expression in PBMCs was negatively correlated with HIF-1α levels and eosinophil counts, but positively correlated with SOD and GPX4 levels.Conclusion: The interplay between hypoxia, oxidative stress, and ferroptosis may be involved in asthma pathogenesis. Based on the findings, Nrf2 may have potential as a biomarker for asthma. However, given the study’s limitations, further research is needed to confirm these associations and fully understand the role of Nrf2 in asthma diagnosis and progression.Keywords: asthma, Nrf2, hypoxia, oxidative stress, ferroptosis