Grape Antioxidant Dietary Fibre Enhances Nrf₂-Linked Redox Protection in Rat Colonic Mucosa

Introduction. Grape pomace combines dietary fibre with poorly extractable and bound polyphenols that can reach the large intestine as a fibre–polyphenol bioactive matrix. This study evaluated whether a 5% grape antioxidant dietary fibre (GADF) diet promotes Nrf₂-linked antioxidant remodelling in proximal and distal rat colonic mucosa.
Methods. Male Wistar rats were fed a control diet with or without 5% GADF supplementation for four weeks. Proximal and distal colonic mucosa were analysed for SIRT1,p-Nrf₂ (ser40), HO-1, Cu/ZnSOD, MnSOD, catalase, GPx and GR by immunohistochemistry. In addition, protein carbonyls and lipid peroxidation were measured in cytosolic and mitochondrial mucosal fractions to determine the extent of cellular oxidative damage. Statistical comparisons were performed using Mann–Whitney U tests; percent changes are descriptive.
Results and Discussion. GADF increased p-Nrf₂ in proximal and distal mucosa by 86% and 96%, respectively (p<0.005), while HO-1 increased by approximately 110% in both regions (p=0.005 and p=0.02). SIRT1 also increased, supporting activation of the SIRT1/p-Nrf₂/HO-1 axis. Concurrently, Cu/ZnSOD and MnSOD decreased significantly in both segments (p<0.01), which may reflect reduced superoxide radical pressure, whereas catalase and GPx showed no significant changes. GR increased most markedly in distal mucosa (+114%, p=0.004), suggesting reinforcement of glutathione-dependent redox recycling. Accordingly, cytosolic oxidative damage was reduced, with lower protein carbonyls in proximal (-69%, p=0.0002) and distal mucosa (-33%, p=0.03), and reduced cytosolic lipid peroxidation in both regions (-44%, p=0.005; -32%, p=0.006). Mitochondrial damage markers showed limited changes.
Conclusions. Dietary supplementation with GADF promoted segment-specific redox remodelling in rat colonic mucosa by combining Nrf₂-linked signalling, GR-dependent recycling and preferential cytosolic protection. These findings support grape pomace-derived fibre as a sustainable functional ingredient for intestinal redox homeostasis.