Eleouny_2026_Tissue.Cell_102_103645

Lead nanoparticles pose a significant threat to avian health, disrupting growth, inducing oxidative stress, and impairing neurological function. This study investigated the protective mechanisms of nano-selenium (Nano-Se) against lead oxide nanoparticles (PbNPs)-induced toxicity in Japanese quails (Coturnix coturnix japonica) using a controlled 28-day experimental design. A total of 360 two-week-old quails were randomly assigned to six treatment groups: (1) control (basal diet), (2) Nano-Se (0.2 mg/kg diet), (3) PbNPs-0.25 (0.25 microg/ml in drinking water), (4) PbNPs-0.50 (0.50 microg/ml), (5) Nano-Se + PbNPs-0.25, and (6) Nano-Se + PbNPs-0.50. Histopathological examination revealed dose-dependent hepatocellular necrosis (60-70% of hepatocytes in the high-dose group), vacuolar degeneration, sinusoidal congestion, and widespread neuronal degeneration with prominent satellitosis and neuronophagia. Immunohistochemical analysis confirmed TNF-alpha-driven neuroinflammation, with intense immunoreactivity in 50-55% of cortical neurons and 65-70% of hepatocytes in PbNPs-exposed groups (3.5-fold increase over controls). These structural lesions were accompanied by a dose-dependent redox crisis, depleting hepatic and neural glutathione S-transferase (GST) activity by 40-50% and elevating lipid peroxidation (MDA 2.5-fold), which correlated with neurotransmitter disruption (serotonin 35%, noradrenaline 45%, acetylcholinesterase 60% reduction) and hepatocyte damage (ALT/AST 3-fold elevation). Remarkably, Nano-Se co-administration attenuated toxicity via three synergistic mechanisms: Nrf2-mediated GST restoration, monoamine oxidase inhibition preserving neurotransmitter balance, and NF-kappaB suppression reducing Kupffer cell infiltration by 65%, with histopathological protection reducing necrosis incidence by 40-50% and suppressing neuroinflammatory TNF-alpha expression by 70-90%. Our findings demonstrate Nano-Se's multi-target efficacy against PbNPs toxicity mediated through selenoprotein-dependent and independent mechanisms, highlighting its potential as a nano-antidote for environmental heavy metal exposure.