Preliminary Associative Evidence on Zinc Oxide Nanoparticle Co-administration in Finasteride-Induced Testicular Toxicity: Inflammatory Markers and Blood–Testis Barrier-Related Proteins in Rats

Finasteride (FNS), a widely used 5α-reductase inhibitor, is associated with reproductive toxicity. However, the molecular mechanisms concerning the blood-testis barrier (BTB) integrity and inflammatory signaling pathways remain unclear. This study evaluated whether zinc oxide nanoparticles (ZnO NPs) were associated with attenuation of FNS-induced testicular injury in rats. Thirty-five male Sprague–Dawley rats were allocated to Control, FNS (5 mg/kg), ZnO NP (30 mg/kg), FNS + ZnO NP 15 mg/kg, and FNS + ZnO NP 30 mg/kg groups and treated orally for 28 days. Sperm quality, reproductive organ weights, serum testosterone and oxidative stress index (OSI), testicular histopathology, junctional-protein immunostaining, RT-qPCR, and Western blot analyses were evaluated. Compared with Control, FNS reduced sperm motility and concentration and increased dead sperm, abnormal morphology, and DNA damage. FNS also increased NF-κB and caspase-3 protein abundance and decreased BCL-2, PI3K, and NRF2. Co-treatment, particularly at 30 mg/kg, was associated with improved sperm motility and concentration, a lower dead sperm rate, reduced histopathological damage, lower NF-κB and caspase-3 abundance, and improvement in selected junctional-protein staining relative to FNS alone. However, abnormal sperm morphology and DNA damage at 30 mg/kg were not significantly different from the FNS group, and PI3K and NRF2 were not significantly restored. Serum testosterone did not differ among groups, whereas OSI showed an overall group effect ( p = 0.007). Tissue-specific oxidative stress markers and pathway phosphorylation were not assessed. These findings provide preliminary, associative evidence that ZnO NPs may partially attenuate FNS-associated testicular injury; they do not establish NF-κB/STAT3 signaling or oxidative stress as causal mechanisms.