In Vivo and In Silico Dissection of Triclosan‐Induced Reproductive Toxicity: Protective Potentials of Nanoselenium and Phytotherapy

Triclosan (TCS) is a widely used antimicrobial agent raising concern about its potential toxicity and adverse effects on fertility. This study investigated the protective efficacy of clomiphene citrate, conventional selenium, nanoselenium and Tribulus terrestris extract (TTE) against TCS-induced toxicity in male rats. Six experimental groups were established: control, TCS-exposed and TCS co-treated with each therapeutic agent. Semen quality; testicular and hepatic biochemical, oxidative and mitochondrial markers; hormone profiles; neurotransmitters; and histopathology were assessed. Specific reproductive (SOX9, inhibin B) and hepatic (Nrf2, NF-κB) markers were quantified to evaluate spermatogenesis, oxidative stress and inflammatory responses. In silico analyses, including molecular docking and molecular dynamics simulations, examined the interactions of TCS with CYP17A1 and GPX4 to elucidate potential mechanisms of enzyme inhibition. The results demonstrated that TCS exposure impaired reproductive and hepatic function, disrupted hormonal balance, induced oxidative stress and tissue damage. Treatments with selenium (conventional and nanoforms) and TTE significantly mitigated these alterations, restoring biochemical and hormonal parameters and improving tissue architecture. Among these, nanoselenium and TTE showed the most pronounced protective effects, emphasizing their comparative efficacy in counteracting TCS-induced toxicity. The findings highlight the potential of nanoselenium and TTE as promising protective agents against TCS-related reproductive and hepatic damage.