Biogenic Synthesis of Iron Oxide Nanoparticles From Bacillus Spizizenii CD418: DSD Optimization and in Vivo Evaluation Against Thioacetamide-Induced Hepatic Encephalopathy in Rats
摘要
Green synthesis of metal nanoparticles (NPs) is increasingly favored as a sustainable alternative to conventional chemical routes. In this study, the culture filtrate of a locally isolated Bacillus spizizenii strain (CD418, partial 16 S rRNA sequence) was employed for the biogenic synthesis of iron oxide nanoparticles (IONPs) with an average size of 15 nm. A definitive screening design (DSD) statistical approach was applied to optimize the process based on IONPs dry weight and optical density (OD), resulting in variability of 93.60% and 99.2%, respectively. The optimized model yielded a desirability value of 0.99, indicating excellent predictive performance. Hepatic encephalopathy (HE), a neuropsychiatric complication associated with acute and chronic liver failure, was experimentally induced in rats using thioacetamide (TAA, 200 mg/kg, intraperitoneally for three consecutive days). IONPs were subsequently administered at a dose of 5 mg/kg for 19 days. Therapeutic efficacy was assessed through biochemical evaluation of liver enzymes (AST, ALT, ALP), oxidative stress markers (GSH, MDA, SOD), and inflammatory mediators (TLR4, IL-1β, COX2, BCL2), alongside histopathological examination of liver and brain tissues. IONP treatment markedly improved all measured biochemical parameters and restored hepatic and neuronal architecture to varying degrees. In conclusion, DSD optimization revealed that IONP biosynthesis is influenced by complex interactions involving main effects, two-factor interactions, and nonlinear (quadratic) components. The biosynthesized IONPs demonstrated significant hepatoneuro-therapeutic potential against TAA-induced damage, highlighting their promise as a nutraceutical nanotherapeutic candidate for managing liver and brain injuries.