Fermentation Status Dictates Organ-Selective Protection of a Millet-Based Dairy Beverage Against Sub-Chronic Lead Toxicity in Rats.

Sub-chronic lead (Pb) exposure induces multi-organ toxicity through oxidative stress and inflammation. Dietary interventions have shown promise, but their effects are often organ nonspecific. This study investigated whether fermentation of a millet-based beverage could differentially direct its protective efficacy against Pb-induced injury in specific organs.Male Wistar rats were exposed to 1 ppm lead acetate in drinking water for 8 weeks and co-administered either: a fermented mix of skimmed milk and malted millet milk (F-Mix), fermented skimmed milk (FSM), or unfermented malted millet milk (UFMM). Hematological, hepatic, renal, inflammatory (TNF-α), hippocampal oxidative stress (Nrf2, GSH, SOD, CAT), acetylcholine, and histopathological parameters were assessed.Pb exposure significantly reduced hemoglobin, increased serum creatinine and BUN, elevated TNF-α, depleted hippocampal antioxidants, and impaired organ histology (p < 0.05 vs. control). Notably, UFMM attenuated Pb-induced hippocampal Nrf2 depletion by 63%, restored GSH by 71%, and preserved hepatic architecture with minimal necrosis. In contrast, F-Mix reduced serum TNF-α by 58% (p < 0.01 vs. Pb group), lowered creatinine by 44%, and BUN by 39%, with preserved renal tubular integrity. Fermented beverages (FSM and F-Mix) showed superior renal protection, while unfermented UFMM was more effective in liver and brain. Fermentation status critically redirects the organ-protective effects of millet-based beverages against Pb toxicity. Unfermented millet milk preferentially activates Nrf2-mediated antioxidant pathways in the brain and liver, while fermentation shifts protection toward the kidneys and systemic inflammation. These findings support the concept that food processing can be leveraged to design targeted nutritional interventions against heavy metal toxicity.