Protective effects of multi-strain probiotics against polystyrene nanoplastic-induced parotid gland toxicity: role of NRF2/HO-1 and NF-κB pathways

Background: Polystyrene nanoplastics (NPs) represent emerging environmental contaminants with potential adverse effects on salivary glands. This study investigated the protective effects of multi-strain probiotics against NPs-induced toxicity in rat parotid glands. Methods: CFU). Treatments were administered orally for 35 days. Oxidative stress markers, histopathological changes, and protein expression were evaluated. Results: NPs exposure significantly increased MDA levels (p < 0.05) and decreased SOD activity and GSH content (p < 0.05). Histopathological examination revealed moderate to severe acinar degeneration (++) and fibrosis (++) in NPs-treated animals. Western blot analysis showed significant downregulation of Bcl-2 (p < 0.01), HO-1 (p < 0.0001), NRF2 (p < 0.01), and AQP5 (p < 0.0001), with upregulation of Caspase-3 (p < 0.0001), NF-κB (p < 0.001), IL-1β (p < 0.001), and TNF-α (p < 0.001). Probiotic supplementation significantly ameliorated oxidative stress (p < 0.05), reduced histopathological damage to mild changes (+), and restored beneficial protein expression while suppressing inflammatory markers (p < 0.01-0.001). Conclusion: This study provides the first evidence that NPs induce significant oxidative stress and tissue damage in parotid glands. Multi-strain probiotics provide substantial protection by activating the NRF2/HO-1 pathway and suppressing inflammation, suggesting a promising therapeutic strategy against nanoplastic-induced oral tissue damage.