Amentoflavone Mitigates Cyclophosphamide-Induced Pulmonary Toxicity: Involvement of -SIRT-1/Nrf2/Keap1 Axis, JAK-2/STAT-3 Signaling, and Apoptosis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Chemicals and Drugs
2.2. Experimental Protocol
2.3. Quantification of the Changes in the Total and Differential Leucocytic Counts in BALF in the Studied Groups
2.4. Assessment of Lactate Dehydrogenase (LDH), Tumor Necrosis Factor-Alpha (TNF-α), Interleukin 15 (IL-15), and Monocyte Chemotactic Protein 1 (MCP-1) in BALF
2.5. Detection of the Levels of TGF-β1 and Nuclear Factor Kappa B (NF-κB) p65 in the Lung Tissues
2.6. Assay of the Tissue Content of Malondialdehyde (MDA) and Total Antioxidant Capacity (TAC) in the Lung Specimens
2.7. Quantification of Nuclear Factor (Erythroid-Derived 2)-like 2 (Nrf2), SIRT-1, and Kelch-like ECH-Associated Protein 1 (Keap1) Contents in the Lung Tissues
2.8. Assessment of Janus Kinase 2 (JAK2) and Signal Transducer and Activator of Transcription 3 (STAT3) in the Pulmonary Tissues
2.9. Determination of Tissue Hydroxyproline and Matrix Metalloproteinase (MMP)-3 and -9 in the Pulmonary Tissues
2.10. Measurement of the Lung Tissue Content of Beclin 1 and LC3-II as Markers of Autophagy
2.11. Analysis of the Histopathological Changes Induced by the Different Treatments in the Lung Tissue Specimens
2.12. Detection and Quantification of the Immunoreactivity to Cleaved Caspase 3 Antibodies in the Pulmonary Tissues
2.13. Assessment of the Effect of CPA with or without AMV on the Electron Microscopic Picture of the Pulmonary Tissues
2.14. Analysis of the Statistical Data
3. Results
3.1. AMV Dose-Dependently Ameliorated the Effect of CPA Administration on the Total and Differential Leucocytic Counts in BALF
3.2. AMV Administration, in a Dose-Dependent Manner, Abrogated the Perturbations in BALF LDH, TNF-α, IL-15, and MCP-1 Levels Induced by CPA Injection
3.3. AMV Dose-Dependently Reversed the Changes Elicited by CPA Injection in TGF-β1, NF-κB (p65), JAK2, and STAT3 Levels in the Pulmonary Tissues
3.4. AMV Dose-Dependently Mitigated the Changes in MDA and TAC Levels in the Pulmonary Tissues Induced via CPA Injection
3.5. AMV Administration Impeded the Changes in Nrf2, SIRT-1, and Keap1 Levels in the Pulmonary Tissues Induced via CPA Injection
3.6. AMV Reversed the Changes Induced by CPA Injection in Hydroxyproline, MMP-3, and MMP-9 Levels in the Pulmonary Tissues
3.7. Effect of the Different Treatments on the Markers of Autophagy
3.8. Effect of the Administration of the Different Doses of AMV on the Histopathological Changes in the Pulmonary Tissues Induced via CPA Injection
3.9. Effect of the Administration of the Different Doses of AMV on the Amount of Collagen Fibers Deposited in the Pulmonary Tissues Induced by CPA Injection
3.10. Effect of the Different Doses of AMV on the Changes in the Immunoexpression of Cleaved Caspase 3 in the Pulmonary Tissues of Rats Injected with CPA
3.11. AMV Combatted the Effects of CPA Injection on the Electron Microscopic Picture of the Specimens Extracted from the Pulmonary Tissues
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Balaha, M.F.; Alamer, A.A.; Aldossari, R.M.; Aodah, A.H.; Helal, A.I.; Kabel, A.M. Amentoflavone Mitigates Cyclophosphamide-Induced Pulmonary Toxicity: Involvement of -SIRT-1/Nrf2/Keap1 Axis, JAK-2/STAT-3 Signaling, and Apoptosis. Medicina 2023, 59, 2119. https://doi.org/10.3390/medicina59122119
Balaha MF, Alamer AA, Aldossari RM, Aodah AH, Helal AI, Kabel AM. Amentoflavone Mitigates Cyclophosphamide-Induced Pulmonary Toxicity: Involvement of -SIRT-1/Nrf2/Keap1 Axis, JAK-2/STAT-3 Signaling, and Apoptosis. Medicina. 2023; 59(12):2119. https://doi.org/10.3390/medicina59122119
Chicago/Turabian StyleBalaha, Mohamed F., Ahmed A. Alamer, Rana M. Aldossari, Alhussain H. Aodah, Azza I. Helal, and Ahmed M. Kabel. 2023. "Amentoflavone Mitigates Cyclophosphamide-Induced Pulmonary Toxicity: Involvement of -SIRT-1/Nrf2/Keap1 Axis, JAK-2/STAT-3 Signaling, and Apoptosis" Medicina 59, no. 12: 2119. https://doi.org/10.3390/medicina59122119