Protective Effects of Atorvastatin on LPS‐Induced Testicular Damage: Modulation of Spermatogenesis via PPAR‐γ, NF‐κB, and NLRP3 Pathways

ABSTRACT Male infertility represents a considerable global health issue, frequently linked to oxidative stress and inflammation‐related dysfunction of the testes. Atorvastatin (ATV), a commonly prescribed statin, has effects that extend beyond merely lowering lipid levels. Recent investigations have increasingly focused on its influence on testicular function and male fertility. This research aims to assess the protective effects of ATV against testicular injury induced by lipopolysaccharide (LPS). Mice were subjected to daily administration of LPS (250 μg/kg; i.p.) for a duration of 7 days. Concurrently, ATV (25 and 50 mg/kg; orally) was administered daily alongside LPS treatment, while a control group received normal saline. ATV was found to elevate testosterone and 5α‐dihydrotestosterone (DHT) levels, reduce oxidative stress by lowering malondialdehyde (MDA) levels and increasing glutathione (GSH) and Nrf2 levels. Additionally, it mitigated inflammation by downregulating tumor necrosis factor‐alpha (TNF‐α), nuclear factor‐kappa B (NF‐κB), MAPK/ERK, and the NLRP3 inflammasome. Moreover, ATV upregulates peroxisome proliferator‐activated receptor gamma (PPARγ), which is essential for cellular metabolism and immune regulation. The findings indicate that ATV possesses significant protective effects against LPS‐induced testicular damage by alleviating oxidative stress, suppressing inflammatory responses, and fostering testicular homeostasis. Its capacity to enhance spermatogenesis underscores its potential as a promising therapeutic strategy for addressing male infertility.