Abstract: FR-PO075
Celastrol Ameliorates Cisplatin Nephrotoxicity by Inhibiting NF-κB and Improving Mitochondrial Function
Session Information
- AKI: Tubules, Metabolism, New Models
October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Yu, Xiaowen, Children's Hospital of Nanjing Medical University, Nanjing, China
- Zhang, Yue, Children's Hospital of Nanjing Medical University, Nanjing, China
- Ding, Guixia, Children's Hospital of Nanjing Medical University, Nanjing, China
- Zhang, Aihua, Children's Hospital of Nanjing Medical University, Nanjing, China
- Jia, Zhanjun, Children's Hospital of Nanjing Medical University, Nanjing, China
- Huang, Songming, Children's Hospital of Nanjing Medical University, Nanjing, China
Background
Celastrol (CE) is an active ingredient of Chinese medicine Tripterygium wilfordii which is clinically used to treat immune diseases. Currently, celastrol is documented as a potent agent for treating cancer and inflammatory disorders. The present study was to investigate the effects of celastrol on cisplatin (Cis) nephrotoxicity and the underlying mechanisms.
Methods
In vivo, C57BL/6 mice were treated with cisplatin (20 mg/kg) with or without celastrol administration (1 mg/kg/day). After 3 days treatment, mice were sacrificed and the kidney and blood samples were collected for analysis. In vitro, renal tubular epithelial cells (RTECs) were treated with cisplatin (5 μg/ml) with or without celastrol treatment (50 nM).
Results
Pretreatment with celastrol markedly ameliorated cisplatin-induced kidney injury as shown by the improved renal function (BUN: Cis group 75.2±10.7 vs. Cis+CE group 31.1±10.9mmol/L, p<0.001; serum creatinine: Cis group 1.2±0.3 vs. Cis+CE group 0.37±0.18 mg/dl, p<0.001; and cystatin C: Cis group 16.0±1.68 vs. Cis+CE group 11.3±1.89 ng/ml, p<0.001), kidney morphology (PAS), and oxidative stress (MDA) in line with a robust blockade of renal tubular injury markers of KIM-1 (-86.97%) and NGAL (-82.09%). Meanwhile, renal apoptosis and inflammation were also strikingly attenuated in celastrol-treated mice. In vitro, celastrol inhibited cisplatin-induced cell apoptosis (-34.31%), suppressed NF-κB activation (-54.53%), and improved mitochondrial function shown by the restored mtDNA copy number (+29%), mitochondrial membrane potential (+61.09%), and OXPHOS activity (+1.67 folds) in cisplatin-treated renal tubular cells.
Conclusion
Our study suggested that celastrol could suppress NF-κB and improve mitochondrial function to protect against cisplatin nephrotoxicity. Celastrol serves as a promising drug for the treatment of AKI.