School of Life and Environmental Science, Wenzhou University, Wenzhou, Zhejiang 325035, China.
School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
Biomed Pharmacother. 2023 Oct;166:115333. doi: 10.1016/j.biopha.2023.115333. Epub 2023 Aug 18.
Ferroptosis is an important pathological process in acute kidney injury (AKI) which could lead to chronic kidney disease (CKD) and end-stage renal disease (ESRD). As an active ingredient of Chinese medicine Tripterygium wilfordii, celastrol has been reported to alleviate inflammation and preclinical studies have confirmed its anticancer effect. In the present study, we investigated the renal protective effects of celastrol against cisplatin induced AKI. Mice were administrated cisplatin by intraperitoneal injection and we found that celastrol reduced serum levels of BUN and creatinine, inhibited renal dysfunction, inflammation and oxidative stress. In addition, renal iron accumulation and ferroptosis were significantly reduced by celastrol treatment. Further mechanistic analyses suggested that Nrf2 is essential for celastrol upregulated GPX4 to alleviate ferroptosis and reduction of LDH release, intracellular iron accumulation and lipid peroxidation. These findings expand the potential uses of celastrol for treatment of various kinds of AKI associated with ferroptosis.
铁死亡是急性肾损伤（AKI）中的一个重要病理过程，可导致慢性肾脏病（CKD）和终末期肾病（ESRD）。作为中药雷公藤的一种有效成分，雷公藤红素已被报道可减轻炎症，临床前研究也证实了其抗癌作用。在本研究中，我们研究了雷公藤红素对顺铂诱导的 AKI 的肾脏保护作用。通过腹腔注射顺铂对小鼠进行处理，我们发现雷公藤红素降低了血清中 BUN 和肌酐的水平，抑制了肾功能障碍、炎症和氧化应激。此外，雷公藤红素治疗还显著减少了肾脏铁积累和铁死亡。进一步的机制分析表明，Nrf2 对于雷公藤红素上调 GPX4 以减轻铁死亡和减少 LDH 释放、细胞内铁积累和脂质过氧化是必需的。这些发现扩展了雷公藤红素用于治疗各种与铁死亡相关的 AKI 的潜在用途。
