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Background <p>Vancomycin (VCM)-induced hepatotoxicity is a significant clinical concern due to its association with oxidative stress, apoptosis, and inflammatory responses. This study investigated the formulation and potential preclinical application of rutin-loaded nanocapsules (RUT-NC) as a hepatoprotective agent against VCM-induced liver injury.</p> Methods <p>Hepatotoxicity was induced in rats through VCM administration, followed by oral treatment with RUT-NC. Liver function, oxidative stress markers, apoptotic proteins, lipid metabolism regulators, and inflammatory cytokines were subsequently evaluated.</p> Results <p>RUT-NC treatment significantly improved liver function parameters, attenuated oxidative stress, and modulated apoptotic pathways by downregulating the expression of <i>p38</i>,<i> p53</i>,<i> caspase-8</i>,<i> miR-122</i>,<i> miR-7</i>, and <i>beclin-1.</i> Furthermore, RUT-NC restored lipid metabolism homeostasis by regulating the expression of PPAR-α, FASN, and SREBP-1. Notably, it exerted potent anti-inflammatory effects by suppressing <i>NF-κB</i>,<i> TNF-α</i>,<i> IL-1β</i>,<i> IL-6</i>,<i> IL-17</i>, and <i>Gasdermin-D</i>, thereby mitigating chronic liver inflammation. The pathological effects of VCM administration on hepatocytes were effectively counteracted by RUT-NC.</p> Conclusion <p>RUT-NC demonstrates promising hepatoprotective properties by enhancing antioxidant defenses, inhibiting apoptosis, regulating lipid metabolism, and reducing inflammation. These findings highlight its potential as a therapeutic intervention for drug-induced liver injury (DILI) and warrant further investigation for clinical application.</p> Graphical Abstract <p></p>

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Rutin-Loaded Nanocapsules Mitigate Vancomycin-Induced Hepatotoxicity: Development, Characterization, Optimization, and In Vivo Evaluation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年6月23日

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  • Mohamed Ibrahim,
  • Mohamed Fouad Mansour,
  • Mahran Mohamed Abd El-Emam,
  • Tarek khamis,
  • Maha S. Kilany,
  • Amira Ebrahim Alsemeh,
  • Asmaa Monir Eltaweel,
  • Milad Reda Qelliny,
  • Mahmoud Mostafa,
  • Marwa Mohamed El Sayed

摘要

Background

Vancomycin (VCM)-induced hepatotoxicity is a significant clinical concern due to its association with oxidative stress, apoptosis, and inflammatory responses. This study investigated the formulation and potential preclinical application of rutin-loaded nanocapsules (RUT-NC) as a hepatoprotective agent against VCM-induced liver injury.

Methods

Hepatotoxicity was induced in rats through VCM administration, followed by oral treatment with RUT-NC. Liver function, oxidative stress markers, apoptotic proteins, lipid metabolism regulators, and inflammatory cytokines were subsequently evaluated.

Results

RUT-NC treatment significantly improved liver function parameters, attenuated oxidative stress, and modulated apoptotic pathways by downregulating the expression of p38, p53, caspase-8, miR-122, miR-7, and beclin-1. Furthermore, RUT-NC restored lipid metabolism homeostasis by regulating the expression of PPAR-α, FASN, and SREBP-1. Notably, it exerted potent anti-inflammatory effects by suppressing NF-κB, TNF-α, IL-1β, IL-6, IL-17, and Gasdermin-D, thereby mitigating chronic liver inflammation. The pathological effects of VCM administration on hepatocytes were effectively counteracted by RUT-NC.

Conclusion

RUT-NC demonstrates promising hepatoprotective properties by enhancing antioxidant defenses, inhibiting apoptosis, regulating lipid metabolism, and reducing inflammation. These findings highlight its potential as a therapeutic intervention for drug-induced liver injury (DILI) and warrant further investigation for clinical application.

Graphical Abstract