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Eugenol Nanoparticles Ameliorate Doxorubicin-Induced Spermatogenic Dysfunction by Inhibiting the PINK1/Parkin and

Yang Fu1,2, Peipei Yuan1,2, Manyv Wang1

  • 1Department of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450046, China, Zhengzhou, 450046, People's Republic of China.

International Journal of Nanomedicine
|December 16, 2024
PubMed
Abstract

Insights

Eugenol nanoparticles protect against doxorubicin-induced testicular damage by reducing oxidative stress and improving sperm motility. This study highlights their potential for mitigating reproductive toxicity.

Area of Science:

  • Reproductive Toxicology
  • Nanomedicine
  • Pharmacology

Background:

  • Doxorubicin (DOX) causes testicular apoptosis and spermatogenic disorders.
  • Eugenol, derived from Eugenia caryophyllata, has limited bioavailability due to poor solubility and stability.
  • Eugenol nanoparticles (ENPs) offer a potential solution to enhance eugenol's therapeutic effects.

Purpose of the Study:

  • To investigate the protective effects of eugenol nanoparticles (ENPs) against doxorubicin-induced reproductive toxicity in mice.
  • To evaluate the efficacy of ENPs in ameliorating DOX-induced spermatogenic dysfunction in vitro and in vivo.

Main Methods:

  • Eugenol was encapsulated in Methoxy-Poly(ethylene glycol)-Poly(lactide-co-glycolide) nanoparticles (mPEG-PLGA-NPs) to create ENPs.
  • In vitro studies assessed the impact of ENPs on doxorubicin-treated GC-1 cells, examining reactive oxygen species (ROS), inflammatory factors, and key protein expressions (PINK1, SCP3).
  • In vivo studies in mice evaluated the effects of ENPs on sperm motility, testicular apoptosis, oxidative stress, and specific signaling pathways (PINK1/Parkin, BNIP3/NIX).

Main Results:

  • ENPs significantly reduced doxorubicin-induced ROS and inflammation in GC-1 cells.
  • ENPs normalized the expression of mitochondrial autophagy protein PINK1 and meiosis-related protein SCP3 in vitro.
  • In vivo, ENPs improved sperm motility, decreased testicular apoptosis and oxidative stress, and modulated relevant signaling pathways, enhancing meiosis-associated factors.

Conclusions:

  • ENPs demonstrate significant protective effects against doxorubicin-induced reproductive toxicity.
  • The developed eugenol-loaded mPEG-PLGA-NPs show promise as a therapeutic strategy for mitigating DOX-induced spermatogenic dysfunction.
  • ENPs represent a safe and effective delivery system with potential clinical applications in reproductive health.
Keywords:
DoxorubicinEugenol nanoparticlesMitochondrial autophagyPINK1/Parkin and BNIP3/NIX signaling pathwaysspermatogenic dysfunction

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