Protopanaxadiol prevents cisplatin-induced acute kidney injury by regulating ferroptosis.

IF 2.8 4区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of Pharmacy and Pharmacology Pub Date : 2024-07-05 DOI:10.1093/jpp/rgae050

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

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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.

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原人参皂苷通过调节铁氧化防止顺铂引起的急性肾损伤

目的：顺铂（CDDP）引起的急性肾损伤（AKI）是一种复杂的危重疾病，目前尚无有效或特异的治疗方法。本研究的目的是评估原人参二醇（PPD）对 CDDP 诱导的 AKI 模型肾脏的保护作用及其可能的机制：方法：在体外，在HK-2中评估PPD的保护作用。方法：在体外，评估 PPD 对 HK-2 的保护作用；在体内，给 KM 小鼠注射 CDDP 诱导 AKI 模型。测定血尿素氮和血清肌酐（SCr），并通过组织病理学检查病理变化。采用免疫染色和 Western 印迹分析蛋白质的表达水平：结果：PPD能提高被CDDP损伤的HK-2细胞的存活率，改善细胞形态，缓解小鼠AKI症状。此外，PPD还能下调TRF的蛋白表达，上调铁蛋白重链、谷胱甘肽过氧化物酶4和铁突变抑制蛋白1的蛋白表达，降低细胞和肾组织中的铁含量，恢复抗氧化防御系统：结论：PPD对顺铂诱导的肾毒性有抑制作用，这可能与通过调节铁代谢和脂质过氧化抑制铁变态反应有关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Pharmacy and Pharmacology 医学-药学

CiteScore

6.60

自引率

0.00%

发文量

审稿时长

3 months

期刊介绍： JPP keeps pace with new research on how drug action may be optimized by new technologies, and attention is given to understanding and improving drug interactions in the body. At the same time, the journal maintains its established and well-respected core strengths in areas such as pharmaceutics and drug delivery, experimental and clinical pharmacology, biopharmaceutics and drug disposition, and drugs from natural sources. JPP publishes at least one special issue on a topical theme each year.

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