Dietary Rutin Ameliorates Nanoparticle Zinc Oxide-Induced Toxicity in Mice by Potentiating Antioxidant Defense Mechanisms

In animal production, nanoparticulate zinc oxide exhibits synergistic antibacterial efficacy coupled with growth-promoting effects, positioning itself as a novel antibiotic alternative with enhanced biosafety profiles. However, its dose-dependent toxicity poses challenges. <b>Objective:</b> The experimental design sought to quantify the protective effects of dietary rutin against zinc-overload-induced damage. <b>Methods:</b> A zinc-overload murine model was established by giving high-dose ZnO nanoparticles (HZn, 5000 mg/kg/day) for 21 days. Mice were then fed rutin at doses of 300, 600, or 1200 mg/kg. Body weight, relative organ indexes, zinc concentrations, serum enzyme activities, and tissue-level indicators of apoptosis, autophagy, mitochondrial function, and antioxidant capacity were measured. <b>Results:</b> The results showed that rutin could not reverse HZn-induced body weight decline but improved relative organ indexes in liver and kidney. It alleviated HZn-induced cell damage and enhanced antioxidant capacity in jejunum and serum through <i>Nrf2</i> activation, without inhibiting HZn-induced zinc elevation. <b>Conclusions:</b> Rutin, especially at 600 mg/kg, can partially restore hepatic function and organ index and mitigate HZn-induced hepatic and jejunal injuries.