Beyond petri dish: small animal models bridge in vitro and in vivo antioxidant assays

Dietary antioxidants, derived mainly from plant-based foods contribute to health promotion by supporting the body’s defense against oxidative stress-related disorders. In vitro assays are widely employed to evaluate the antioxidant capacities of food-derived compounds, providing rapid and cost-effective insights into their radical scavenging and reducing potential. However, these methods do not account for factors such as digestion, absorption, metabolism, and tissue distribution, which determine the physiological relevance of antioxidants. Therefore, in vivo models are essential to complement in vitro findings, enabling a more accurate assessment of bioavailability, mechanisms of action, and health benefits in a biological context. Small animal models provide versatile platforms to bridge this gap, offering genetic tractability, conserved pathways, and cost-effective tools for functional validation of dietary antioxidants. In this review, we summarize the antioxidant defense mechanisms and experimental approaches utilized in zebrafish, C. elegans, and fruit fly to investigate the impact of dietary antioxidants. Key outcomes of antioxidative action in these models include the reduction of reactive oxygen species, upregulation of endogenous defense systems, protection of biomacromolecules from oxidative damage, and lifespan extension. Furthermore, this review outlines future directions for utilizing these small animals as translational models in the investigation of food-derived antioxidants.