Selenium nanoparticles attenuate Klebsiella pneumoniae-induced mastitis via the suppression of ferroptosis and the antioxidant restoration in goat

Klebsiella pneumoniae (K. pneumoniae)-induced mastitis poses a severe threat to livestock health with limited therapeutic options. Selenium nanoparticles (SeNPs) offer promising biocompatibility and antioxidant potential, but their efficacy and mechanism against bacterial mastitis remain unexplored. This study demonstrated that the oral administration of SeNPs (20 μg/kg BW) attenuated K. pneumoniae-induced mastitis in goats. The treatment reduced histopathological damage and neutrophil infiltration, while it restored anti-inflammatory interleukin (IL)-10 mRNA expression and suppressed pro-inflammatory IL-1β and IL-6 mRNA levels. Ultrasonography and Doppler analysis confirmed that mammary hemodynamics and echotextural abnormalities were improved. SeNPs supplementation contributed to increased concentrations of selenium in the serum, enhanced the activity of mammary glutathione, activated the peroxiredoxin 6 (PRDX6)/ selenophosphate synthetase 2 (SEPHS2) axis, and upregulated glutathione peroxidase 4 (GPX4) expression. Immunofluorescence revealed that SeNPs strengthened the PRDX6-SEPHS2 interaction to improve the activity of GPX4. Crucially, SeNPs suppressed ferroptosis by inhibiting nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy, reducing iron overload and lipid peroxidation, and attenuating NCOA4-ferritin heavy chain 1 colocalization. The findings established that SeNPs concurrently target inflammatory, antioxidant, hemodynamic, and ferroptotic pathways to prevent bacterial mastitis, suggesting a novel intervention for the prevention and control of mastitis.