Mn₂O₃ Nanoparticles as a Potential Neuronal Threat Despite Hepatorenal Benefits-Implications for Dietary...

Manganese (Mn) is an essential trace element crucial for antioxidant defense, metabolism, and neuronal function, yet both deficiency and excess may induce oxidative stress and organ-specific damage. This study investigated the effects of dietary manganese exclusion and replacement of standard MnCO₃ with Mn₂O₃ nanoparticles on redox status and oxidative damage in rats. Twenty-four male Wistar rats were divided into three groups: control (K) receiving 65 mg/kg Mn as MnCO₃, manganese-deficient (B), and nanoparticle-supplemented (N) receiving 65 mg/kg Mn as Mn₂O₃ nanoparticles. After 12 weeks, tissues were analyzed for oxidative stress markers and antioxidant enzyme activities. Manganese deficiency resulted in decreased plasma SOD activity, increased lipid peroxidation, and severe oxidative-nitrosative damage in the brain and jejunum, despite hepatic compensatory mechanisms. Mn₂O₃ nanoparticle supplementation enhanced hepatic and renal antioxidant capacity, reducing oxidative damage in these organs. However, nanoparticles induced pronounced neurotoxicity, characterized by GSH depletion, elevated DNA damage (8-OHdG), protein nitration (3-NT), and caspase activation in brain tissue. These findings demonstrate that while Mn₂O₃ nanoparticles offer improved bioavailability and hepatorenal benefits, they pose significant neurotoxic risks, necessitating caution in dietary supplementation strategies.