L-theanine attenuates intestinal oxidative injury in mice through modulation of ferroptosis pathways.

Oxidative stress impairs intestinal health in animals. As a potential antioxidant, L-theanine exerts anti-inflammatory and antioxidant effects. However, its biological functions and underlying mechanisms in intestinal oxidative damage remain unclear. This study aimed to investigate the protective effect of L-theanine against diquat-induced intestinal oxidative damage in mice and explore its potential molecular mechanisms. The results showed that dietary L-theanine supplementation significantly enhanced intestinal antioxidant capacity (reducing the levels of reactive oxygen species, malondialdehyde and hydrogen peroxide and elevating the activities of antioxidant enzymes), alleviated inflammation (downregulating pro-inflammatory cytokine levels and upregulating interleukin-10 mRNA expression), improved intestinal integrity (enhancing morphology, reducing permeability and upregulating tight junction-related genes), and boosted mitochondrial function (increasing mitochondrial membrane potential, ATP content and mitochondrial function-related gene expression) in oxidatively stressed mice. Concomitantly, L-theanine attenuated intestinal iron overload (inhibiting Fe2+ accumulation and upregulated ferritin heavy chain 1 expression) and suppressed the ferroptosis pathway (upregulating nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione peroxidase 4 (GPX4), and solute carrier family 7 member 11 expression). In conclusion, L-theanine alleviates intestinal oxidative damage in oxidatively stressed mice by enhancing intestinal antioxidant capacity and inhibiting ferroptosis, a protective effect that may be mediated by the activation of the Nrf2/GPX4 signaling pathway.