We evaluated the effectiveness of pharmacological doses of grape-seed proanthocyanidin extract (GSPE) in reversing intestinal barrier alterations and local inflammation in female Wistar rats fed a long-term obesogenic diet. Animals were fed a 17-week cafeteria diet (CAF diet), supplemented with daily GSPE doses (100 or 500 mg kg-1 body weight) during the final two weeks. CAF diet enhanced the intestinal permeation of an orally administered marker (ovalbumin, OVA) and increased the plasma levels of tumor necrosis factor-α (TNF-α) and lipopolysaccharides (LPS) in 2-3-fold. Ex vivo Ussing chamber assays showed a 55-70% reduction in transepithelial electrical resistance (TEER) and increased the TNF-α secretions in both small and large intestinal sections with a 25-fold increment in the ileum. Ileal tissues also presented a 4-fold increase of myeloperoxidase (MPO) activity. Both GSPE-treatments were able to restitute TEER values in the ileum and colon and to reduce plasma LPS to basal levels without a dose-dependent effect. However, effects on the OVA permeation and TNF-α secretion were dose and section-specific. GSPE also reduced ileal MPO activity and upregulated claudin 1 gene expression. This study provides evidence of the efficacy of GSPE-supplementation ameliorating diet-induced intestinal dysfunction and metabolic endotoxemia when administered at the end of a long-term obesogenic diet.
Keywords: Ussing chamber; flavan-3-ol; gut; inflammation; obesity; tight junction; transepithelial electrical resistance.