Protective effects of selenium against paclitaxel-induced testicular damage via modulation of oxidative stress,...

Paclitaxel (PTX) is an effective antineoplastic agent whose clinical utility is limited by toxic effects on the male reproductive system. This study aimed to elucidate the reproductive toxicological mechanisms of PTX-induced testicular injury and to evaluate the protective effects of selenium (Se) against chemically mediated cellular and endocrine damage. Male Sprague-Dawley rats were exposed to PTX, with selenium administered at doses of 0.5 mg/kg and 1 mg/kg. Reproductive toxicity was assessed through sperm analysis and measurement of reproductive hormones, including follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone. Oxidative stress markers (MDA) and antioxidant enzymes (SOD, GPx), as well as pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), were quantified by ELISA. Molecular mechanisms were investigated by evaluating Keap1/Nrf2/HO-1 and HMGB1/TLR4/NF-κB signaling pathways using Western blot analysis, while RAGE and NLRP3 gene expression levels were determined by RT-PCR. Testicular damage, apoptosis, and DNA oxidation were further examined by histopathological, immunohistochemical, and immunofluorescence analyses targeting Bax, Bcl-2, caspase-3, and 8-OHdG. PTX exposure resulted in marked reproductive toxicity characterized by impaired sperm parameters, suppression of FSH, LH, and testosterone levels, increased oxidative stress, inflammatory activation, apoptotic signaling, and DNA damage in testicular tissue. Selenium treatment significantly mitigated these adverse effects in a dose-dependent manner by restoring endocrine balance, enhancing antioxidant defense, suppressing inflammatory and apoptotic pathways, and improving spermatogenesis. Collectively, these findings demonstrate that selenium exerts a protective role against PTX-induced reproductive toxicity by modulating key chemical-biological interaction pathways involved in testicular injury.