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Effects of fluconazole on oxidative stress and cellular well-being in erythrocytes
Muhammad Sikandar1, Maham Abdul Bari Khan2, Kashif Jilani2
1Institutes of Biomedical Sciences, Shanxi University, 92 Wucheng Road, Taiyuan, 030006, Shanxi province, China.
Abstract:
Fluconazole is a triazole antifungal medication that alters the stability and permeability of the fungal cell membrane, leading to impaired growth and replication of fungi in treating widespread fungal infections. However, its effects on human cells need to be further explored. In this study, we used erythrocytes to examine the effects of fluconazole on oxidative stress and cellular well-being. Erythrocytes were exposed at different therapeutic levels of fluconazole (150-300 μM) for 48 h to evaluate oxidative stress by examining the cellular responses of key antioxidant enzymes like superdismutase (SOD), catalase (CAT), and Glutathionine (GPx). Additionally, the study analyzed the role of calcium ions (Ca2+) in eryptosis and changes in cell size, highlighting the wide range of integrated outcomes of fluconazole treatment. In parallel, through in vitro analysis of the GSE58910 dataset, differentially expressed genes linked to oxidative stress were identified, demonstrating key genes such as Glutathionine GPX4, Glutathionine disulphide reductase GSR, thrombospondin TXN, and others pivotal for ROS detoxification and cellular stability. The integration of in vivo and in vitro findings is crucial to a comprehensive understanding of fluconazole's mechanisms, offering key discernments for clinical practices in antifungal therapies.
Insights
Fluconazole, an antifungal drug, can induce oxidative stress and cell death in human red blood cells (erythrocytes) at therapeutic concentrations. This study reveals fluconazole
Area of Science:
- Pharmacology
- Toxicology
- Cell Biology
Background:
- Fluconazole is a widely used antifungal agent targeting fungal cell membranes.
- Its impact on human cells, particularly concerning oxidative stress, requires further investigation.
Purpose of the Study:
- To investigate the effects of fluconazole on human erythrocytes, focusing on oxidative stress and eryptosis.
- To identify molecular mechanisms and gene expression changes associated with fluconazole exposure.
Main Methods:
- Exposure of human erythrocytes to varying concentrations of fluconazole (150-300 μM) for 48 hours.
- Assessment of antioxidant enzyme activity (SOD, CAT, GPx), calcium ion levels, and cell morphology.
- In vitro analysis of the GSE58910 dataset to identify differentially expressed genes related to oxidative stress.
Main Results:
- Fluconazole exposure led to increased oxidative stress markers and induced eryptosis in erythrocytes.
- Key genes involved in oxidative stress response and detoxification, such as GPX4 and GSR, were identified.
- Fluconazole treatment altered calcium ion homeostasis and cell size in erythrocytes.
Conclusions:
- Fluconazole exhibits potential toxicity to human erythrocytes by inducing oxidative stress and eryptosis.
- Understanding these cellular effects is crucial for optimizing antifungal therapy and patient safety.
- Integrated in vivo and in vitro data provide insights into fluconazole's broader impact on cellular integrity.
