Chrysophanol Relieves Cisplatin-Induced Nephrotoxicity via Concomitant Inhibition of Oxidative Stress, Apoptosis, and Inflammation

Abstract

Cisplatin (CDDP) is one of the most frequently prescribed chemotherapy medications. However, its nephrotoxicity which often leads to acute kidney injury (AKI), greatly limits its clinical application. Chrysophanol (CHR), a mainly active anthraquinone ingredient, possesses various biological and pharmacological activities. In this study, we aimed to investigate the underlying protective mechanisms of CHR against CDDP-induced AKI (CDDP-AKI) using C57BL/6 mouse and human proximal tubule epithelial cells. In vivo, we found that pre-treatment with CHR greatly relieved CDDP-AKI and improved the kidney function and morphology. The mechanistic studies indicated that it might alleviate CDDP-AKI by inhibiting oxidative stress, apoptosis, and IKKβ/IκBα/p65/transcription factor nuclear kappa B (NF-κB) inflammation signaling pathway induced by CDDP. Moreover, we found that the cell viability of HK2 cells reduced by CDDP was partially rescued by CHR pre-incubation. Flow cytometry results further indicated that CHR pre-incubation suppressed CDDP induced cellular reactive oxygen species (ROS) generation and inhibited cell apoptosis in a dose-dependent manner. In summary, our results suggested that CHR might be a novel therapy for CDDP-induced AKI.

Chrysophanol Ameliorates Hemin-Induced Oxidative Stress and Endoplasmic Reticulum Stress by Regulating MicroRNA-320-5p/Wnt3a Pathway in HT22 Cells

“…Our data revealed that CHR could reduce hemin-induced oxidative stress in HT22 cell; this result is similar to the role of CHR in other diseases. For example, Ma et al reported that CHR relieves cisplatin-induced nephrotoxicity via concomitant inhibition of oxidative stress and apoptosis [62]. Zhao et al demonstrated that CHR alleviates nitrosation/oxidative stress injury in focal cerebral ischemia/reperfusion [17].…”

The progress and prospect of natural components in rhubarb (Rheum ribes L.) in the treatment of renal fibrosis

“…Another study demonstrated that chrysophanol alleviated cisplatin (CDDP)-induced acute kidney injury (AKI). Its pharmacological mechanism may primarily act through the inhibition of CDDP-induced oxidative stress, apoptosis and the NF-κB signaling pathway ( Ma et al, 2021 ).…”

“…Another study demonstrated that chrysophanol alleviated cisplatin (CDDP)-induced acute kidney injury (AKI). Its pharmacological mechanism may primarily act through the inhibition of CDDP-induced oxidative stress, apoptosis and the NF-κB signaling pathway (Ma et al, 2021). Studies have found that aloe-emodin can reduce the protein levels of PI3K, Akt and mTOR in UUO mice, improve biochemical indicators such as Scr and BUN in UUO mice, and inhibit the mRNA expression of TGF-β1, collagen type I, collagen type IV and FN.…”