Intestinal-targeted delivery of mixture of probiotics via MgO/chitosan/alginate nanoparticles for mitigating lead(II)-induced multi-organ toxicity.

Lead(II) (Pb(II)) is a widespread environmental contaminant known to induce oxidative stress, inflammation, and multi-organ damage in both humans and animals. Conventional remediation methods, such as free probiotic supplementation, are often compromised by gastric acid, which significantly reduces the probiotics' targeted delivery to the small intestine, where Pb(II) exerts much of its toxicity. Addressing this challenge, the present study introduces a novel approach: encapsulating a mixture of probiotics (Lactobacillus rhamnosus, Lactobacillus helveticus, and Lactobacillus casei) within magnesium oxide (MgO)/chitosan/alginate nanoparticles. In vitro experiments demonstrated a substantial release of probiotics at pH 7.4, approximately 90%, compared to minimal release at pH 3.5. Furthermore, this encapsulated mixture of probiotics exhibited enhanced protective effects on RAW 264.7 macrophage-like cells, with cell viability increasing by 17% compared to a free mixture of probiotics. For in vivo validation, male Wistar rats were allocated into four groups: control, Pb(II)-exposed, Pb(II)-exposed mixture of probiotics, and Pb(II)-exposed encapsulated mixture of probiotics. After 30 days, liver enzyme levels (ALT, AST, ALP) in the experimental groups displayed a significant increase (P < 0.05) compared to the control, but a significant decrease was observed in the treatment groups compared to the Pb(II)-exposed group. Hepatic oxidative stress indices (increased MDA and decreased SOD and catalase) in the Pb(II)-exposed and treatment groups changed compared to the control (P < 0.05), with significant improvement in the treatments. As well as histological examination and gene expression (Bax, Bcl-2, p53, Caspase-3, IL-6, TNF-α) confirmed relative improvement and significant changes (P < 0.05) in the treatment groups compared to the Pb(II)-exposed groups, highlighting the protective effects of the treatments.