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Protective Effects of Atorvastatin on LPS-Induced Testicular Damage: Modulation of Spermatogenesis via PPAR-γ, NF-κB,

Rania Elgohary1, Amany A El-Fadaly2, Abeer Salama2

  • 1Narcotics, Ergogenics and Poisons Department, Medical Research and Clinical Studies Institute, National Research Centre (NRC), Cairo, Egypt.

Journal of Applied Toxicology : JAT
|July 4, 2025
PubMed

Insights

Atorvastatin (ATV) protects against testicular damage by reducing oxidative stress and inflammation. This study shows ATV enhances male fertility by improving testicular function and spermatogenesis.

Area of Science:

  • Reproductive Biology
  • Pharmacology
  • Toxicology

Background:

  • Male infertility is a significant health concern, often linked to testicular oxidative stress and inflammation.
  • Atorvastatin (ATV), a lipid-lowering drug, is being investigated for its broader effects on testicular function.
  • Lipopolysaccharide (LPS) is known to induce testicular injury, making it a relevant model for studying protective agents.

Purpose of the Study:

  • To evaluate the protective effects of Atorvastatin (ATV) against lipopolysaccharide (LPS)-induced testicular injury in mice.
  • To investigate ATV's impact on oxidative stress markers, inflammatory pathways, and hormone levels in the testes.
  • To assess ATV's potential to improve testicular homeostasis and spermatogenesis.

Main Methods:

  • Mice received daily intraperitoneal injections of LPS (250 μg/kg) for 7 days to induce testicular injury.
  • Mice were concurrently treated with oral Atorvastatin (ATV) at doses of 25 and 50 mg/kg.
  • Control groups received normal saline, and various biochemical and molecular markers of oxidative stress and inflammation were analyzed.

Main Results:

  • ATV treatment significantly increased testosterone and 5α-dihydrotestosterone (DHT) levels.
  • ATV reduced oxidative stress by decreasing malondialdehyde (MDA) and increasing glutathione (GSH) and Nrf2 levels.
  • ATV suppressed inflammatory markers including tumor necrosis factor-alpha (TNF-α), nuclear factor-kappa B (NF-κB), MAPK/ERK, and the NLRP3 inflammasome, while upregulating PPARγ.

Conclusions:

  • Atorvastatin demonstrates significant protective effects against LPS-induced testicular damage.
  • ATV alleviates testicular dysfunction by mitigating oxidative stress and suppressing inflammatory responses.
  • The findings suggest ATV holds promise as a therapeutic agent for male infertility associated with testicular injury and inflammation.
Keywords:
MAPKNLRP3PPARγlipopolysaccharidetestis

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