Naringin Alleviates Digoxin-induced Nephrotoxicity via Regulating Nrf2/HO-1 and PI3K/ AKT/TGF-β Cascades in Rats' Renal Tissues.

IF 2.6 4区医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current pharmaceutical biotechnology Pub Date : 2025-04-29 DOI:10.2174/0113892010340746250421065424

Hoda K Said, Al Shaimaa Ibrahim Rabie, Amira S A Said, Mohammad M AlAhmad, Raghda R S Hussein, Mohamed Mady, Asmaa M El-Kalaawy, Khalid S Hashem, Amr E Ahmed

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Abstract

Background: Nephrotoxicity limits the clinical application of digoxin. One area that might be useful is the mechanical knowledge of altered renal function and renal impairment. We hypothesized that co-administration of naringin would affect digoxin nephrotoxicity by alleviating the altered renal oxidative/ antioxidant redox and apoptotic cascade.

Method: 40 male Wistar Albino rats (200 ± 50 g) were grouped into 4, every group included (n= 7), control, Nar., Dig. and Nar. + dig. Groups. Colorimetric estimation of kidney functions and renal oxidative/ antioxidant redox were done.

Results: Comparing digoxin alone, the concomitant administration of digoxin and naringin restored renal antioxidant/ oxidative redox, redistributed Nrf2, HO-1 mRNA exposure with a concomitant down-regulation of NF-κB, AKT and PI3K mRNA expressions. Moreover, a significant decrease of Smad3 and transforming growth factor-β (TGF- β) protein concentrations with a simultaneous rise of Smad7 were noticed in Nar. + dig. Arm when compared to Dig. group.

Conclusion: The co-administration of naringin and digoxin can mitigate digoxin-mediated nephrotoxicity by introducing antioxidant action. This is done by maintaining effects on renal oxidative/antioxidant cycle and lethality via regulating AKT/ PI3k/ Smad3/ Smad7 signaling pathways.

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柚皮苷通过调节肾组织Nrf2/HO-1和PI3K/ AKT/TGF-β级联反应减轻地高辛所致大鼠肾毒性

背景：肾毒性限制了地高辛的临床应用。一个可能有用的领域是肾功能改变和肾功能损害的机械知识。我们假设柚皮苷的联合使用可能通过减轻肾脏氧化/抗氧化氧化还原和凋亡级联反应的改变来影响地高辛的肾毒性。方法：雄性Wistar Albino大鼠40只（200±50 g），随机分为4组，每组7只，对照组7只。,挖。Nar。+挖。组。比色法测定肾功能和肾脏氧化/抗氧化氧化还原。结果：与单独使用地高辛相比，地高辛和柚皮苷联合使用可恢复肾脏抗氧化/氧化氧化还原、Nrf2、HO-1 mRNA的再分布，同时下调NF-κB、AKT和PI3K mRNA的表达。此外，在Nar中发现Smad3和转化生长因子-β (TGF- β)蛋白浓度显著降低，Smad7同时升高。+挖。手臂与Dig相比。组。结论：柚皮苷与地高辛联用可通过引入抗氧化作用减轻地高辛所致肾毒性。这是通过调节AKT/ PI3k/ Smad3/ Smad7信号通路维持对肾脏氧化/抗氧化周期和致死率的影响来实现的。

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

Current pharmaceutical biotechnology 医学-生化与分子生物学

CiteScore

5.60

自引率

3.60%

发文量

203

审稿时长

6 months

期刊介绍： Current Pharmaceutical Biotechnology aims to cover all the latest and outstanding developments in Pharmaceutical Biotechnology. Each issue of the journal includes timely in-depth reviews, original research articles and letters written by leaders in the field, covering a range of current topics in scientific areas of Pharmaceutical Biotechnology. Invited and unsolicited review articles are welcome. The journal encourages contributions describing research at the interface of drug discovery and pharmacological applications, involving in vitro investigations and pre-clinical or clinical studies. Scientific areas within the scope of the journal include pharmaceutical chemistry, biochemistry and genetics, molecular and cellular biology, and polymer and materials sciences as they relate to pharmaceutical science and biotechnology. In addition, the journal also considers comprehensive studies and research advances pertaining food chemistry with pharmaceutical implication. Areas of interest include: DNA/protein engineering and processing Synthetic biotechnology Omics (genomics, proteomics, metabolomics and systems biology) Therapeutic biotechnology (gene therapy, peptide inhibitors, enzymes) Drug delivery and targeting Nanobiotechnology Molecular pharmaceutics and molecular pharmacology Analytical biotechnology (biosensing, advanced technology for detection of bioanalytes) Pharmacokinetics and pharmacodynamics Applied Microbiology Bioinformatics (computational biopharmaceutics and modeling) Environmental biotechnology Regenerative medicine (stem cells, tissue engineering and biomaterials) Translational immunology (cell therapies, antibody engineering, xenotransplantation) Industrial bioprocesses for drug production and development Biosafety Biotech ethics Special Issues devoted to crucial topics, providing the latest comprehensive information on cutting-edge areas of research and technological advances, are welcome. Current Pharmaceutical Biotechnology is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the latest and most important developments.