Mapping a sustainable approach with whey-biosynthesized silver nanocomposites versus chemically synthesized silver nanoparticles in a chronic hippocampal toxicity rat model.

Silver nanoparticles (AgNPs) are increasingly utilized in food-contact materials and dairy processing systems. However, the chronic oral effects of these materials have not been sufficiently characterized. This study compared hippocampal responses to chemically synthesized AgNPs (8-11 nm) suspended in whey-based medium (WBM) at measured silver concentrations with those from biogenic silver nanocomposites (AgNCs; 13.3 ± 3.6 nm). These were administered orally to male Sprague-Dawley rats (120-150 g, n = 5 per group) for 90 days. AgNCs were biosynthesized by fermenting WBM with Lactobacillus acidophilus using 4 mM or 6 mM AgNO3 precursors, yielding 0.431 mg/mL and 0.647 mg/mL silver, respectively, as confirmed by ICP-OES with 99.99% efficiency. Chemical AgNPs were matched accordingly. Treatments included saline control (nC), WBM (wC), fermented WBM (LwC), low-dose chAg4w/bioAg4Lw (4.31 mg/day, approximately 28.8 mg/kg/day), and high-dose chAg6w/bioAg6Lw (6.47 mg/day, approximately 43.1 mg/kg/day) via 10 mL daily oral gavage. Chemical AgNPs elevated hippocampal malondialdehyde (MDA) and nitric oxide (NO) levels, reduced glutathione peroxidase (GPx), superoxide dismutase (SOD), and glutathione (GSH), and altered Nrf2/SOD/NF-κB/iNOS/caspase-3 expression. Transmission electron microscopy (TEM) confirmed mitochondrial swelling, chromatin condensation, and myelin unraveling. In contrast, biogenic AgNCs preserved redox/gene homeostasis and ultrastructure akin to controls. These findings demonstrate that chemical AgNPs induce oxidative, apoptotic, and myelin damage at realistic chronic oral doses, while whey/L. acidophilus AgNCs provide a safer-by-design alternative for antimicrobial applications.