Grape Seed Extract Dose-Responsively Decreases Disease Severity in a Rat Model of Mucositis; Concomitantly Enhancing Chemotherapeutic Effectiveness in Colon Cancer Cells

被引：46
作者：
Cheah, Ker Yeaw [1 ,2 ]
Howarth, Gordon Stanley [2 ,3 ]
Bastian, Susan Elaine Putnam [1 ]
机构：
[1] Univ Adelaide, Sch Agr Food & Wine, Adelaide, SA 5005, Australia
[2] Children Youth & Womens Hlth Serv, Ctr Paediat & Adolescent Gastroenterol, Adelaide, SA, Australia
[3] Univ Adelaide, Sch Anim & Vet Sci, Adelaide, SA 5005, Australia
来源：
PLOS ONE | 2014年 / 9卷 / 01期
关键词：
SMALL-INTESTINAL MUCOSITIS; PROANTHOCYANIDIN EXTRACT; LINE CACO-2; BREATH TEST; 5-FLUOROURACIL; APOPTOSIS; EXPRESSION; GROWTH; METHOTREXATE; INFLAMMATION;
D O I：
10.1371/journal.pone.0085184
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
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 mu g/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.
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页数：11
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