Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/87178
Citations
Scopus Web of Science® Altmetric
?
?
Type: Journal article
Title: Grape seed extract dose-responsively decreases disease severity in a rat model of mucositis; concomitantly enhancing chemotherapeutic effectiveness in colon cancer cells
Author: Cheah, K.
Howarth, G.
Bastian, S.
Citation: PLoS One, 2014; 9(1):e85184-1-e85184-11
Publisher: Public Library of Science
Issue Date: 2014
ISSN: 1932-6203
1932-6203
Statement of
Responsibility: 
Ker Yeaw Cheah, Gordon Stanley Howarth, Susan Elaine Putnam Bastian
Abstract: OBJECTIVE: Mucositis is a serious disorder of the gastrointestinal tract that results from cancer chemotherapy. We investigated the effects of increasing grape seed extract doses on the severity of chemotherapy in a rat model and its coincident impact on chemotherapeutic effectiveness in colon cancer cells. DESIGN: Female Dark Agouti rats were gavaged with grape seed extract (400-1000 mg/kg) or water (day 3-11) and were injected intraperitoneally with 5-Fluorouracil (150 mg/kg) or saline (control) on day 9 to induce mucositis. Daily metabolic data were collected and rats were sacrificed on day 12. Intestinal tissues were collected for histological and myeloperoxidase analyses. Caco-2 cell viability was examined in response to grape seed extract in combination with 5-Fluorouracil by 3-(4,5-Dimethylthiazol-2yl)-2,5-diphenyl-tetrazolium bromide) assay. RESULTS: Compared with 5-Fluorouracil controls, grape seed extract (400-1000 mg/kg) significantly decreased the histological damage score (P<0.05) in the jejunum. Grape seed extract (1000 mg/kg) increased jejunal crypt depth by 25% (P<0.05) in 5-Fluorouracil treated rats compared to 5-Fluorouracil controls, and attenuated the 5-Fluorouracil -induced reduction of mucosal thickness (25%, P<0.05). Grape seed extract (600 mg/kg) decreased myeloperoxidase activity by 55% (P<0.01) compared to 5-Fluorouracil controls. Grape seed extract was more effective at ameliorating 5-Fluorouracil induced intestinal injury, with effects most pronounced in the proximal jejunum. Grape seed extract (10-25 ug/mL) significantly enhanced the growth-inhibitory effects of 5-Fluorouracil by 26% (P<0.05) in Caco-2 cells and was more potent than 5-Fluorouracil at 50-100 µg/mL. CONCLUSION: Grape seed extract may represent a new therapeutic option to decrease the symptoms of intestinal mucositis while concurrently impacting on the viability of colon cancer cells.
Keywords: Intestinal Mucosa; Jejunum; Caco-2 Cells; Animals; Humans; Rats; Fluorouracil; Peroxidase; Antioxidants; Administration, Oral; Injections, Intraperitoneal; Severity of Illness Index; Cell Proliferation; Cell Survival; Female; Mucositis; Grape Seed Extract
Rights: © 2014 Cheah et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
RMID: 0030012155
DOI: 10.1371/journal.pone.0085184
Appears in Collections:Animal and Veterinary Sciences publications

Files in This Item:
File Description SizeFormat 
hdl_87178.pdfPublished version1.18 MBAdobe PDFView/Open


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.