Probiotic Supplementation Attenuates Polystyrene Nanoplastic-Induced Pancreatic Injury through Modulation of...

Polystyrene nanoplastics (PsNPs) represent an emerging environmental threat with potential adverse effects on pancreatic tissue. This study investigated whether probiotic supplementation (PB) could attenuate PsNPs-induced pancreatic injury by modulating oxidative stress, inflammation, and P2X7R/Caspase-1 signaling. Forty male Sprague-Dawley rats were divided into five groups: control, probiotic (PB 10¹⁰), PsNPs (100 nm, 10 mg/kg/day), PsNPs + PB 10⁹, and PsNPs + PB 10¹⁰. After 35 days of oral administration, oxidative stress markers, inflammatory cytokines, P2X7R/Caspase-1 gene expression, signaling proteins (NF-κB, PI3K, p-PI3K, p38 MAPK, TGF-β), histopathology, and immunohistochemistry (Bcl-2, Caspase-3, Insulin, P2X7 and Caspase-1) were evaluated. PsNPs significantly upregulated P2X7R and Caspase-1 expression (Sp < 0.0001), elevated NF-κB levels (p < 0.0001), increased IL-1β and TNF-α, and induced oxidative stress with elevated MDA, depleted SOD (p < 0.001), and reduced GSH (p < 0.01). Histopathology revealed inflammatory infiltration and cellular degeneration. Insulin immunoreactivity decreased while Caspase-3 increased. Probiotic co-treatment at 101⁰ CFU/day significantly attenuated P2X7R/Caspase-1 upregulation, reduced NF-κB expression, restored SOD activity and GSH levels, normalized cytokines, and preserved Insulin immunoreactivity. PsNPs induce pancreatic injury through P2X7R/Caspase-1/NF-κB signaling activation. Multi-strain probiotic supplementation exerts dose-dependent protective effects by modulating purinergic signaling and restoring antioxidant capacity.