Ellagic Acid and Ellagic Acid Functionalized Selenium Nanoparticles Ameliorate Cyclophosphamide-Induced Testicular Injury by Modulating Oxidative Stress.

Cyclophosphamide is known to induce oxidative stress-mediated reproductive injury. The present study investigated the prophylactic efficacy of ellagic acid and ellagic acid functionalized selenium nanoparticles against cyclophosphamide-induced testicular injury in rats. Prophylactic treatment with ellagic acid (10, 20, 30, and 40 mg kg-1 doses) and ellagic acid functionalized selenium nanoparticles (1, 2, 3, and 4 mg kg-1 doses) was administered to Wistar rats prior to a single acute dose of cyclophosphamide (200 mg kg-1). Evaluation of biochemical parameters related to oxidative stress, antioxidant defence, lipid metabolism, and sperm functions along with histological alterations in the testis was carried out. Exposure to cyclophosphamide significantly elevated lipid peroxidation, depleted GSH, and suppressed enzymatic antioxidants, including superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione S-transferase in the testis, accompanied by increased total and esterified cholesterol in testicles and severe testicular degeneration. Prophylactic treatment with ellagic acid and ellagic acid functionalized selenium nanoparticles significantly reduced oxidative stress, enhanced activities of antioxidant enzymes, and improved testicular histoarchitecture and sperm indices. Notably, ellagic acid functionalized selenium nanoparticles offered protection comparably similar to ellagic acid, underscoring its potential as a promising nano-formulation in mitigating cyclophosphamide-induced testicular injury by modulating oxidative stress and biochemical alterations towards control. The close relationship between antioxidant imbalance and cyclophosphamide-induced testicular injury was revealed by the findings. Prophylactic treatment with ellagic acid functionalized selenium nanoparticles was identified as a powerful nano-enabled intervention supporting a selenium-based nanotherapeutics-based strategy for reproductive protection.