Mucositis is a common side-effect of high-dose
chemotherapy regimens.
Grape seed extract (GSE) represents a rich source of
proanthocyanidins with the potential to decrease oxidative damage and
inflammation within the gastrointestinal tract. We evaluated GSE for its capacity to decrease the severity of
chemotherapy-induced
mucositis in vitro and in vivo. In vitro: GSE was administered to IEC-6 intestinal epithelial cells prior to damage induced by
5-Fluorouracil (5-FU). Cell viability was determined by
neutral red assay. In vivo: Female Dark Agouti rats (130-180 g) were gavaged with 1 ml GSE (400 mg/kg) daily (day 3-11) and received
5-FU (150 mg/kg) by intraperitoneal (i.p.) injection on day nine to induce
mucositis. Rats were sacrificed at day 12 and intestinal tissues collected for
myeloperoxidase and
sucrase activity assays and histological analyses. Statistical analysis was performed by one-way ANOVA. GSE prevented the decrease in IEC-6 cell viability induced by
5-FU (p < 0.01). Compared with
5-FU controls, GSE significantly reduced
myeloperoxidase activity by 86% and 27% in the proximal jejunum (p < 0.001) and distal ileum (p < 0.05) respectively; decreased qualitative histological scores of damage (p < 0.05) in the proximal jejunum; increased villus height in the proximal jejunum (17%; p < 0.05) and distal ileum (50%; p < 0.01), and attenuated the 5-FU-induced reduction of mucosal thickness by 16% in the jejunum (p < 0.05) and 45% in the ileum (p < 0.01). GSE partially protected IEC-6 cells from 5-FU-induced cytotoxicity and ameliorated intestinal damage induced by
5-FU in rats. GSE may represent a promising prophylactic adjunct to conventional
chemotherapy for preventing intestinal
mucositis.