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Betaine Alleviates Favipiravir-induced Ovarian and Uterine Toxicity by Regulating Oxidative, Inflammatory, Cellular

Ramazan Bülbül1, Hasan Şimşek2, Nurhan Akaras3

  • 1Department of Gynecology and Obstetrics, Faculty of Medicine, Aksaray University, Aksaray, 68100, Türkiye. ramazan.bulbul@aksaray.edu.tr.

Reproductive Sciences (Thousand Oaks, Calif.)
|July 17, 2026
PubMed

Insights

Betaine (BTN) protects against favipiravir (FVP)-induced ovarian and uterine toxicity by reducing oxidative stress, inflammation, and apoptosis. This antioxidant agent restored hormonal balance and preserved reproductive tissue integrity in rats.

Area of Science:

  • Reproductive toxicology
  • Pharmacology
  • Biochemistry

Background:

  • Favipiravir (FVP), an antiviral medication, may pose risks to reproductive health.
  • Ovarian and uterine tissues are susceptible to drug-induced toxicity.
  • Understanding the protective mechanisms of agents like betaine (BTN) is crucial for mitigating adverse effects.

Purpose of the Study:

  • To investigate the protective role of betaine (BTN) against favipiravir (FVP)-induced ovarian and uterine toxicity.
  • To elucidate the underlying mechanisms, including oxidative stress, inflammation, apoptosis, and hormonal dysregulation.
  • To evaluate the impact of BTN on reproductive tissue integrity and function.

Main Methods:

  • Wistar rats were assigned to control, BTN, FVP, and FVP + BTN groups.
  • Ovarian and uterine tissues, along with blood samples, were collected after 10 days.
  • Analyses included biochemical assays, qRT-PCR, histology, and immunohistochemistry to assess various biomarkers and tissue damage.

Main Results:

  • FVP significantly increased oxidative stress, inflammation, apoptosis, and autophagy markers while decreasing antioxidant levels and steroidogenesis genes.
  • FVP administration led to reduced serum levels of AMH, E2, FSH, and LH.
  • Concomitant BTN treatment reversed most FVP-induced changes, restored hormonal balance, reduced inflammatory and apoptotic markers, and preserved tissue histology.

Conclusions:

  • Favipiravir (FVP) induces multifaceted toxicity in ovarian and uterine tissues through oxidative, inflammatory, apoptotic, and hormonal pathways.
  • Betaine (BTN) demonstrates significant protective effects against FVP-induced reproductive toxicity.
  • BTN mitigates FVP's adverse effects, preserving ovarian and uterine tissue integrity and function.
Keywords:
BetaineFavipiravirOvarianOxidative stressToxicityUterine

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