Probiotic Supplementation Attenuates Polystyrene Nanoplastic-Induced Pancreatic Injury through Modulation of Oxidative Stress, Inflammation, and P2X7 Receptor/Caspase-1 Signaling Pathway in Rats

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. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2026.