Grape seed extract protects IEC-6 cells from chemotherapy-induced cytotoxicity and improves parameters of small intestinal mucositis in rats with experimentally-induced mucositis

Date

2009

Authors

Cheah, K.
Howarth, G.
Yazbek, R.
Wright, T.
Whitford, E.
Payne, C.
Butler, R.
Bastian, S.

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Journal article

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Cancer Biology & Therapy, 2009; 8(4):382-390

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Ker Y. Cheah, Gordon S. Howarth, Roger Yazbeck, Tessa H. Wright, Eleanor J. Whitford, Caroline Payne, Ross N Butler and Susan E.P. Bastian

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Abstract

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 (130-180g) were gavaged with 1ml GSE (400mg/kg) daily (day 3-11) and received 5-FU (150mg/kg) by intraperitoneal (i.p.) injection on day 9 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.

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Link to a related website: https://www.tandfonline.com/doi/pdf/10.4161/cbt.8.4.7453?needAccess=true, Open Access via Unpaywall

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© 2009 Landes Bioscience

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