Dose–Time Effects of Dietary Nano-Selenium on Growth, Antioxidant Capacity, and Selenoprotein Expression in Juvenile Large-Scale Loach (Paramisgurnus dabryanus)

Selenium (Se) is an essential trace element for aquatic animals, but its narrow margin between nutritional requirement and toxicity necessitates precise supplementation strategies. Nano-selenium (Nano-Se) has emerged as a promising alternative, yet its dose- and time-dependent effects on the Paramisgurnus dabryanus remain poorly understood. This study employed a central composite design (CCD) within response-surface methodology (RSM) to systematically investigate the interactive effects of dietary Nano-Se concentration (0–4 mg Se/kg diet) and feeding duration (20–60 days) on growth performance, and further evaluated hepatic antioxidant parameters as well as expression profiles of 12 selenoprotein- and glutathione-metabolism-related genes. The RSM models for weight-gain rate (WGR) and specific growth rate (SGR) were highly significant (R2_Adj = 0.972 and 0.855, respectively; p < 0.001), revealing that the two factors act independently (TS term not significant, p > 0.05). Optimal growth was achieved at 1.0 mg/kg Nano-Se, with feeding duration showing a continuous positive effect on WGR (maximum at 60 d) but a plateau effect on SGR after 30 days. The medium dose (1.0 mg/kg) maintained stable antioxidant capacity and induced the strongest gene–enzyme coupling at 40 days (e.g., selenoprotein O1 (selenoo1) vs. SOD: ρ = 0.90, p < 0.001). The low dose (0.5 mg/kg) suppressed SOD and GSH-Px activities, whereas the high dose (3.0 mg/kg) disrupted positive coupling and caused an “uncoupling” phenomenon with up-regulation of antioxidant enzymes but down-regulation of transaminases. Twelve functional genes were clustered into three response modules: selenoprotein synthesis (Cluster I, including glutathione peroxidase 1 (gpx1) and tRNA-selenocysteine-1-associated protein (trnau1ap)), GSH-dependent secondary defense (Cluster II), and GSH regeneration/metabolism (Cluster III). Notably, gpx1 and other antioxidant-defense genes were prioritized under adequate Se supply, whereas trnau1ap (SECp43), a potential master switch for selenoprotein translation, was globally down-regulated under long-term high-Se exposure. In conclusion, the optimal Nano-Se supplementation for juvenile P. dabryanus is 1.0 mg/kg for 40 days, providing a theoretical basis for precision selenium nutrition in farmed fish.