Protective properties of grape-seed proanthocyanidins in human ex vivo acute colonic dysfunction induced by dextran sodium sulfate

Purpose Anti-inflammatory and barrier-protective properties have been attributed to proanthocyanidins in the context of intestinal dysfunction, however little information is available about the impact of these phytochemicals on intestinal barrier integrity and immune response in the human. Here we assessed the putative protective properties of a grape-seed proanthocyanidin extract (GSPE) against dextran sodium sulfate (DSS)-induced acute dysfunction of the human colon in an Ussing chamber system. Methods Human proximal and distal colon tissues from colectomized patients were submitted ex vivo for a 30-min preventive GSPE treatment (50 or 200 mu g mL(-1)) followed by 1-h incubation with DSS (12% w v(-1)). Transepithelial electrical resistance (TEER), permeation of a fluorescently-labeled dextran (FD4) and proinflammatory cytokine release [tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta] of colonic tissues were determined. Results DSS reduced TEER (45-52%) in both the proximal and distal colon; however, significant increments in FD4 permeation (fourfold) and TNF-alpha release (61%) were observed only in the proximal colon. The preventive GSPE treatment decreased DSS-induced TEER loss (20-32%), FD4 permeation (66-73%) and TNF-alpha release (22-33%) of the proximal colon dose-dependently. The distal colon was not responsive to the preventive treatment but showed a reduction in IL-1 beta release below basal levels with the highest GSPE concentration. Conclusions Our results demonstrate potential preventive effects of GSPE on human colon dysfunction. Further studies are required to test whether administering GSPE could be a complementary therapeutic approach in colonic dysfunction associated with metabolic disorders and inflammatory bowel disease.