Journal
BIOMEDICINE & PHARMACOTHERAPY
Volume 166, Issue -, Pages -Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2023.115333
Keywords
Celastrol; Cisplatin; Acute kidney injury; Ferroptosis; GPX4
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Ferroptosis is a crucial process in AKI that can lead to CKD and ESRD. Celastrol, an active ingredient of Tripterygium wilfordii, has anti-inflammatory and anti-cancer effects. This study found that celastrol protected against cisplatin-induced AKI by reducing inflammation, oxidative stress, renal iron accumulation, and ferroptosis. Mechanistic analysis revealed that celastrol upregulated GPX4 via Nrf2, alleviating ferroptosis and reducing LDH release, intracellular iron accumulation, and lipid peroxidation. These findings suggest the potential use of celastrol for treating AKI associated with ferroptosis.
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 anti-cancer 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.
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