Protopanaxadiol prevents cisplatin-induced acute kidney injury by regulating ferroptosis

Zeyu Song; Zhenyuan Li; Tao Pan; Teng Liu; Baifang Gong; Zhixia Wang; Ke Liu; Huaying Fan

doi:10.1093/jpp/rgae050

Protopanaxadiol prevents cisplatin-induced acute kidney injury by regulating ferroptosis

J Pharm Pharmacol. 2024 May 6:rgae050. doi: 10.1093/jpp/rgae050. Online ahead of print.

Authors

Zeyu Song¹, Zhenyuan Li¹, Tao Pan¹, Teng Liu¹, Baifang Gong¹, Zhixia Wang¹, Ke Liu², Huaying Fan¹

Affiliations

¹ School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, PR China.
² Shandong Boyuan Biomedical Co., Ltd, Yantai 264003, PR China.

PMID: 38708970
DOI: 10.1093/jpp/rgae050

Abstract

Objectives: Acute kidney injury (AKI) caused by cisplatin (CDDP) is a complex, critical illness with no effective or specific treatment. The purpose of the study was to assess the protective effect of protopanaxadiol (PPD) on the kidneys in CDDP-induced AKI models and its possible mechanisms.

Methods: In vitro, the protection of PPD was assessed in HK-2. KM mice were injected with CDDP to induce AKI models in vivo. The determination of blood urea nitrogen and serum creatinine (SCr) was performed, and pathological changes were examined by histopathological examination. Immunostaining and western blot analyses were used to analyze the expression levels of proteins.

Results: PPD can increase the viability of HK-2 cells damaged by CDDP, improve cell morphology, and alleviate the symptoms of AKI in mice. In addition, PPD can down-regulate the protein expression of TRF and up-regulate the protein expression of Ferritin heavy chain, Glutathione peroxidase 4, and ferroptosis suppressor protein 1 reduce the iron content in cells and kidney tissues, and restore the antioxidant defense system.

Conclusion: PPD has an inhibitory effect on cisplatin-induced nephrotoxicity, which may be related to the inhibition of ferroptosis by regulating iron metabolism and lipid peroxidation.

Keywords: acute kidney injury; cisplatin; ferroptosis; nephrotoxicity; protopanaxadiol.

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