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Updated: Mar 8, 2026
A Doxorubicin-induced Cardiomyopathy Model in Adult Zebrafish
Published on: June 7, 2018
Protective effects of dioscin against doxorubicin-induced nephrotoxicity via adjusting FXR-mediated oxidative stress
Yimeng Zhang1, Youwei Xu1, Yan Qi1
1College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
Abstract:
Dioscin shows active effects against renal ischemia/reperfusion injury and lipopolysaccharide-induced inflammatory kidney injury, however, little is known concerning the role of it on doxorubicin (Dox)-induced nephrotoxicity. In the present study, in vivo test of Dox-induced nephrotoxicity in rats and in vitro model in NRK-52E cells were developed. The results showed that dioscin significantly attenuated cell injury, obviously reduced ROS level in vitro, and markedly decreased the levels of BUN, Cr, MDA, and notably increased the levels of SOD, GSH and GSH-Px in rats. Mechanistic studies showed that dioscin significantly increased the levels of p-AMPKα, Nrf2, HO-1 and GST by activation of FXR against oxidative stress. In addition, dioscin suppressed the nuclear translocation of NF-κB and HMGB1, and subsequently decreased the mRNA levels of IL-1β, IL-6, and TNF-α against inflammation. These results were further validated by knockdown of FXR using siRNA silencing, and abrogation of FXR using NDB (a FXR inhibitor) in NRK-52E cells, and the results suggested that the protective effect of dioscin against Dox- induced nephrotoxicity via adjusting FXR-mediated signal to suppress oxidative stress and inflammation. In addition, molecular docking assay showed that dioscin directly targeted with FXR through competing with Helix12 (H12) by hydrogen bonding, hydrophobic effect and electrostatic interactions. In a word, our data showed that dioscin is a novel and potent FXR agonist to suppress inflammation and oxidative stress against Dox-induced nephrotoxicity.
Insights
Dioscin protects against doxorubicin (Dox)-induced kidney injury by activating the FXR pathway. This natural compound reduces oxidative stress and inflammation, offering a potential therapeutic strategy for nephrotoxicity.
Area of Science:
- Pharmacology
- Toxicology
- Natural Products
Background:
- Doxorubicin (Dox) is a potent chemotherapy agent with significant nephrotoxicity.
- Dioscin has shown protective effects in other kidney injury models, but its role in Dox-induced nephrotoxicity is unclear.
Purpose of the Study:
- To investigate the protective effects and underlying mechanisms of dioscin against Dox-induced nephrotoxicity in vitro and in vivo.
Main Methods:
- In vivo studies using Dox-treated rats and in vitro studies with NRK-52E cells.
- Assessment of oxidative stress markers (ROS, MDA, SOD, GSH, GSH-Px) and inflammatory cytokines (IL-1β, IL-6, TNF-α).
- Mechanistic investigations involving FXR, AMPK, Nrf2, NF-κB, HMGB1 signaling pathways, and molecular docking.
Main Results:
- Dioscin significantly attenuated Dox-induced kidney injury, reduced oxidative stress, and decreased inflammatory responses.
- Dioscin activated FXR, leading to increased Nrf2, HO-1, and GST levels, while suppressing NF-κB and HMGB1 nuclear translocation.
- Molecular docking confirmed direct binding of dioscin to FXR.
Conclusions:
- Dioscin exerts protective effects against Dox-induced nephrotoxicity by activating FXR, thereby suppressing oxidative stress and inflammation.
- Dioscin is a potent FXR agonist with potential therapeutic applications for chemotherapy-induced kidney damage.
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