Celastrol is a natural bioactive compound extracted from the medicinal plant Tripterygium wilfordii Hook F. It exhibits 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. This study aims 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 was pretreated with the desired concentrations of celastrol (200 nM, 100 nM, and 50 nM) for 24 h. The cells were treated with 50 μM cisplatin for a further 24 h to see whether cisplatin caused the same or less toxicity compared to the vehicle control group. Alkaline comet assay was performed for genotoxicity assessment. Genotoxicity evaluation revealed that celastrol caused a statistically significant reduction in DNA damage. Oxidative stress parameters were evaluated by measuring the 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 ameliorated the protein carbonylation level. Likewise, celastrol pretreatment improved the GR and CAT activities. However, no significant difference was observed in GPx and SOD activities. 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.

中文翻译：

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雷公藤红素预处理作为对抗顺铂引起的肾毒性的治疗选择。

雷公藤红素是从药用植物雷公藤中提取的天然生物活性化合物。它具有免疫抑制、抗炎和抗氧化活性。顺铂是一种常用的化疗药物，用于治疗多种肿瘤。虽然治疗上非常有效，但它可能引起肾毒性，导致剂量减少或停止治疗。本研究旨在阐明雷公藤红素在顺铂引起的肾毒性中的治疗潜力。研究了雷公藤红素预处理对顺铂诱导的氧化应激和遗传毒性的可能保护作用。用所需浓度的雷公藤红素（200 nM、100 nM 和 50 nM）预处理大鼠肾上皮细胞系 NRK-52E 24 小时。将细胞用 50 μM 顺铂再处理 24 小时，以观察与载体对照组相比，顺铂是否引起相同或更少的毒性。进行碱性彗星测定以进行遗传毒性评估。遗传毒性评估显示，雷公藤红素可显着减少 DNA 损伤，具有统计学意义。通过测量谷胱甘肽 (GSH) 和蛋白质羰基 (PC) 水平以及测量谷胱甘肽过氧化物酶 (GPx)、谷胱甘肽还原酶 (GR)、过氧化氢酶 (CAT) 和超氧化物歧化酶 (SOD) 的酶活性来评估氧化应激参数。雷公藤红素预处理增加了细胞的GSH含量并改善了蛋白质羰基化水平。同样，雷公藤红素预处理改善了 GR 和 CAT 活性。然而，GPx 和 SOD 活性没有观察到显着差异。根据这些发现，雷公藤红素治疗可能是减少顺铂引起的肾毒性的一种治疗选择。需要进一步研究来阐明其治疗潜力。