1. The Protective Effect of Fluorofenidone against Cyclosporine A-Induced Nephrotoxicity.
- Author
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Chen Y, Wang N, Yuan Q, Qin J, Hu G, Li Q, Tao L, Xie Y, and Peng Z
- Subjects
- Animals, Apoptosis drug effects, Dose-Response Relationship, Drug, Kidney pathology, Male, Protective Agents pharmacology, Rats, Rats, Sprague-Dawley, Cyclosporine toxicity, Fibrosis prevention & control, Kidney injuries, Pyridones pharmacology
- Abstract
Background/aims: Cyclosporine A (CsA) is an immunosuppressant drug that is used during organ transplants. However, its utility is limited by its nephrotoxic potential. This study aimed to investigate whether fluorofenidone (AKF-PD) could provide protection against CsA-induced nephrotoxicity., Methods: Eighty-five male Sprague-Dawley rats were divided into 5 groups: drug solvent, CsA, CsA with AKF-PD (250, 500 mg/kg/day), and CsA with pirfenidone (PFD, 250 mg/kg/day). Tubulointerstitial injury index, extracellular matrix (ECM) deposition, expression of type I and IV collagen, transforming growth factor (TGF)-β1, platelet-derived growth factor (PDGF), Fas ligand (FASL), cleaved-caspase-3, cleaved-poly(ADP-ribose) polymerase (PARP)-1, and the number of transferase-mediated nick end-labeling (TUNEL)-positive renal tubule cells were determined. In addition, levels of TGF-β1, FASL, cleaved-caspase-3, cleaved-PARP-1, and number of annexin V-positive cells were determined in rat proximal tubular epithelial cells (NRK-52E) treated with CsA (20 μmol/L), AKF-PD (400 μg/mL), PFD (400 μg/mL), and GW788388 (5 μmol/L)., Results: AKF-PD (250, 500 mg/kg/day) significantly reduced tubulointerstitial injury, ECM deposition, expression of type I and IV collagen, TGF-β1, PDGF, FASL, cleaved-caspase-3, cleaved-PARP-1, and number of TUNEL-positive renal tubule cells in the CsA-treated kidneys. In addition, AKF-PD (400 μg/mL) significantly decreased TGF-β1, FASL, cleaved-caspase-3, and PARP-1 expression in NRK-52E cells and further reduced the number of annexin V-positive cells., Conclusion: AKF-PD protect kidney from fibrosis and apoptosis in CsA-induced kidney injury., (© 2019 The Author(s) Published by S. Karger AG, Basel.)
- Published
- 2019
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