Celastrol Pretreament As a Therapeutic Option Against Cisplatin Induced Nephrotoxicity

Celastrol is a natural, bioactive compound extracted from the medicinal plant Tripterygium wilfordii Hook F. It has immunosuppressive, anti-inflammatory, and antioxidant activities. Cisplatin is a commonly used chemotherapeutic drug in the treatment of a wide range of tumors. Although very effective therapeutically, it can cause nephrotoxicity leading to dose reduction or discontinuation of treatment. In this study, it was aimed to clarify the therapeutic potential of celastrol in cisplatin induced nephrotoxicity. The possible protective effects of celastrol pretreatment against cisplatin induced oxidative stress and genotoxicity were investigated. A rat kidney epithelial cell line NRK-52E cells were pretreated with the desired concentrations of celastrol (200 nM, 100 nM, 50 nM) for 24 h. The cells were treated with 50 µM cisplatin for a further 24 h to see if cisplatin caused the same or less toxicity compared to the vehicle control group. Alkaline comet assay was performed for genotoxicity assessment. Genotixicity evaluation revealed that celastrol provided a statistically significant reduction in DNA damage. Oxidative stress parameters were evaluated by glutathione (GSH) and protein carbonyl (PC) levels and also by measuring the enzyme activities of glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT) and superoxide dismutase (SOD) enzymes. Celastrol pretreatment increased the GSH content of the cells and ameloriated the protein carbonylation level. Likewise, celastrol pretreatment improved the GR and CAT activity. However, GPx and SOD activity did not show significant difference. In the light of these findings celastrol treatment could be a therapeutic option to reduce cisplatin induced nephrotoxicity. Further studies are needed for the clarification of its therapeutic potential.