Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/87178
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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 |
Editor: | Muders, M. |
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. |
DOI: | 10.1371/journal.pone.0085184 |
Published version: | http://dx.doi.org/10.1371/journal.pone.0085184 |
Appears in Collections: | Animal and Veterinary Sciences publications Aurora harvest 2 |
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hdl_87178.pdf | Published version | 1.18 MB | Adobe PDF | View/Open |
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