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Background and Objective <p>Doxorubicin (Doxo) exhibits a central role in cancer chemotherapy, yet its clinical potential is substantially undermined by the risk of significant adverse effects. Propolis is a naturally derived substance with notable biological effects, yet its translation into effective therapies is restricted by its low water solubility and inadequate bioavailability. To overcome these limitations, propolis was encapsulated into nanoparticles, and their protective effect against Doxo-induced hepatotoxicity was investigated, with a focus on comparing prophylactic versus therapeutic administration. </p> Methods <p>Adult rats were assigned to five groups: Control group; Doxo group given a dose of (10 mg/kg); Propolis-loaded nanoparticles (PNPs) group receiving PNPs (50 mg/kg); PNPs+Doxo group treated with PNPs prior to Doxo administration; and a Doxo+PNPs group receiving Doxo followed by PNPs administration. Serum liver enzymes (ALT and AST), inflammatory mediators (TNF-α and IL-6), oxidative stress biomarkers (SOD, CAT, GR, GSH and TBARS), and the apoptotic marker caspase-3 were evaluated. In addition, histopathological analysis was performed to assess liver tissue architecture and pathological changes. </p> Results <p>Compared with the Doxo-treated group, PNPs significantly improved liver function, as indicated by decreased ALT and AST serum levels. Additionally, PNPs treatment significantly alleviated oxidative stress in hepatic tissue, demonstrated by decreased TBARS levels and increased expression of SOD, CAT, GR, and GSH, along with significantly reducing hepatic DNA frequency breakage. Moreover, IL-6, TNF-α, and caspase-3 were markedly reduced in PNPs co-treatment groups (p &lt; 0.05) versus the Doxo group. Notably, therapeutic administration of PNPs following Doxo exposure significantly improved GR activity and reduced TNF-α levels compared to the prophylactic group, while no significant differences were observed in the other measured biomarkers. Histopathological examination revealed substantial mitigation of Doxo-induced hepatic degeneration in PNPs co-treated groups. </p> Conclusion <p>Overall, PNPs effectively protect against Doxo-induced hepatotoxicity through antioxidant, anti-apoptotic, and anti-inflammatory mechanisms, supporting their potential as a promising adjunct therapy to chemotherapeutics.</p>

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Protective Effect of Propolis Loaded Nanoparticles Against Doxorubicin-Induced Liver Injury in Rats

  • 期刊论文

  • 发表日期：

    2026年5月22日

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  • Shrouk S. Ismail,
  • Sabah G. El-Banna,
  • Aly B. Okab,
  • Sara A. Alsakhawy

摘要

Background and Objective

Doxorubicin (Doxo) exhibits a central role in cancer chemotherapy, yet its clinical potential is substantially undermined by the risk of significant adverse effects. Propolis is a naturally derived substance with notable biological effects, yet its translation into effective therapies is restricted by its low water solubility and inadequate bioavailability. To overcome these limitations, propolis was encapsulated into nanoparticles, and their protective effect against Doxo-induced hepatotoxicity was investigated, with a focus on comparing prophylactic versus therapeutic administration.

Methods

Adult rats were assigned to five groups: Control group; Doxo group given a dose of (10 mg/kg); Propolis-loaded nanoparticles (PNPs) group receiving PNPs (50 mg/kg); PNPs+Doxo group treated with PNPs prior to Doxo administration; and a Doxo+PNPs group receiving Doxo followed by PNPs administration. Serum liver enzymes (ALT and AST), inflammatory mediators (TNF-α and IL-6), oxidative stress biomarkers (SOD, CAT, GR, GSH and TBARS), and the apoptotic marker caspase-3 were evaluated. In addition, histopathological analysis was performed to assess liver tissue architecture and pathological changes.

Results

Compared with the Doxo-treated group, PNPs significantly improved liver function, as indicated by decreased ALT and AST serum levels. Additionally, PNPs treatment significantly alleviated oxidative stress in hepatic tissue, demonstrated by decreased TBARS levels and increased expression of SOD, CAT, GR, and GSH, along with significantly reducing hepatic DNA frequency breakage. Moreover, IL-6, TNF-α, and caspase-3 were markedly reduced in PNPs co-treatment groups (p < 0.05) versus the Doxo group. Notably, therapeutic administration of PNPs following Doxo exposure significantly improved GR activity and reduced TNF-α levels compared to the prophylactic group, while no significant differences were observed in the other measured biomarkers. Histopathological examination revealed substantial mitigation of Doxo-induced hepatic degeneration in PNPs co-treated groups.

Conclusion

Overall, PNPs effectively protect against Doxo-induced hepatotoxicity through antioxidant, anti-apoptotic, and anti-inflammatory mechanisms, supporting their potential as a promising adjunct therapy to chemotherapeutics.