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Protective Effects of Hesperidin on Letrozole-Induced Neurotoxicity: Involvement of Oxidative Stress, Apoptotic

İdris Ayhan1, Munevver Nazlican Kaplan1, Demet Dondu Kasim1

  • 1Department of Pharmacology, Faculty of Medicine, Pamukkale University, Denizli, Türkiye.

Journal of Biochemical and Molecular Toxicology
|March 12, 2026
PubMed

Insights

Hesperidin protects against letrozole-induced neurotoxicity by reducing oxidative stress, apoptosis, and inflammation. This study reveals hesperidin

Area of Science:

  • Neuroscience
  • Pharmacology
  • Biochemistry

Background:

  • Letrozole, an aromatase inhibitor for breast cancer, may cause neurotoxicity.
  • Mechanisms of letrozole-induced neurotoxicity are not fully understood.
  • Hesperidin, a flavonoid, possesses antioxidant and anti-inflammatory properties.

Purpose of the Study:

  • To investigate the neurotoxic effects of letrozole.
  • To evaluate the neuroprotective potential of hesperidin against letrozole-induced neurotoxicity.

Main Methods:

  • Adult female rats were administered letrozole alone or with hesperidin for 4 weeks.
  • Biochemical analyses assessed oxidative stress (TOS/TAS).
  • Gene expression (Bax, Bcl2), cytokine levels (IL-1, IL-6, TNF-α, IL-10), and histopathology were evaluated.

Main Results:

  • Letrozole induced oxidative stress, apoptosis, and inflammation, with cortical damage.
  • Hesperidin treatment counteracted these effects, restoring redox balance and reducing inflammation.
  • Hesperidin normalized apoptotic gene expression and ameliorated histological damage.

Conclusions:

  • Hesperidin demonstrates significant neuroprotection against letrozole-induced neurotoxicity.
  • Neuroprotection is mediated by restoring redox balance, regulating apoptosis, and suppressing inflammation.
  • Hesperidin shows potential therapeutic value for managing letrozole-induced neurotoxicity.
Keywords:
apoptosishesperidinletrozoleneurotoxicityoxidative stress

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