Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Pathophysiol. Nov 15, 2017; 8(4): 176-187
Published online Nov 15, 2017. doi: 10.4291/wjgp.v8.i4.176
Effects of commercially produced almond by-products on chemotherapy-induced mucositis in rats
Alexandra L Whittaker, Ying Zhu, Gordon S Howarth, Chi S Loung, Susan E P Bastian, Michelle G Wirthensohn
Alexandra L Whittaker, Gordon S Howarth, Chi S Loung, School of Animal and Veterinary Sciences, the University of Adelaide, Roseworthy Campus, Roseworthy, SA 5371, Australia
Ying Zhu, Susan E P Bastian, Michelle G Wirthensohn, School of Agriculture, Food and Wine, the University of Adelaide, Glen Osmond, SA 5064, Australia
Gordon S Howarth, Department of Gastroenterology, Women’s and Children’s Hospital, North Adelaide, SA 5006, Australia
Author contributions: Whittaker AL, Zhu Y, Howarth GS, Bastian SEP and Wirthensohn MG designed the research; Whittaker AL, Zhu Y and Loung CS performed the research; Whittaker AL, Zhu Y and Loung CS analyzed the data; Whittaker AL, Zhu Y, Howarth GS, Bastian SEP and Wirthensohn MG wrote the paper.
Supported by Horticulture Australia Limited.
Institutional review board statement: The use of animals for teaching, research or experimentation is regulated by State legislation - the South Australian Animal Welfare Act 1985. The University of Adelaide is licensed under the Act to acquire and use animals only when approval has been granted by its Animal Ethics Committee (AEC). No animal may be held or used for any purpose until written approval has been obtained from the AEC. Internal approval for this study was obtained from the AEC.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Animal Ethics Committee of the University of Adelaide (protocol number: s2014-162) and conducted in accordance with the provisions of the Australian Code for the Care and Use of Animals for Scientific Purposes.
Conflict-of-interest statement: The authors have no conflict of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Michelle G Wirthensohn, Research Fellow, School of Agriculture, Food and Wine, the University of Adelaide, Glen Osmond, SA 5064, Australia. michelle.wirthensohn@adelaide.edu.au
Telephone: +61-8-83130431
Received: March 17, 2017
Peer-review started: March 20, 2017
First decision: May 3, 2017
Revised: May 20, 2017
Accepted: June 30, 2017
Article in press: July 3, 2017
Published online: November 15, 2017
Processing time: 240 Days and 11.6 Hours
Abstract
AIM

To determine if almond extracts reduce the severity of chemotherapy-induced mucositis as determined through biochemical, histological and behavioural markers.

METHODS

Intestinal mucositis is a debilitating condition characterized by inflammation and ulceration of the gastrointestinal mucosa experienced by cancer patients undergoing chemotherapy. Certain bioactive plant products have shown promise in accelerating mucosal repair and alleviating clinical symptoms. This study evaluated almond extracts for their potential to reduce the severity of chemotherapy-induced mucositis in Dark Agouti rats. Female Dark Agouti rats were gavaged (days 3-11) with either PBS, almond hull or almond blanched water extract at two doses, and were injected intraperitoneally with 5-fluorouracil (5-FU-150 mg/kg) or saline on day 9 to induce mucositis. Burrowing behavior, histological parameters and myeloperoxidase activity were assessed.

RESULTS

Bodyweight was significantly reduced in rats that received 5-FU compared to saline-treated controls (P < 0.05). Rats administered 5-FU significantly increased jejunal and ileal MPO levels (1048%; P < 0.001 and 409%; P < 0.001), compared to healthy controls. Almond hull extract caused a pro-inflammatory response in rats with mucositis as evidenced by increased myeloperoxidase activity in the jejunum when compared to 5-FU alone (rise 50%, 1088 ± 96 U/g vs 723 ± 135 U/g, P = 0.02). Other extract-related effects on inflammatory activity were minimal. 5-FU significantly increased histological severity score compared to healthy controls confirming the presence of mucositis (median of 9.75 vs 0; P < 0.001). The extracts had no ameliorating effect on histological severity score in the jejunum or ileum. Burrowing behavior was significantly reduced in all chemotherapy-treated groups (P = 0.001). The extracts failed to normalize burrowing activity to baseline levels.

CONCLUSION

Almond extracts at these dosages offer little beneficial effect on mucositis severity. Burrowing provides a novel measure of affective state in studies of chemotherapy-induced mucositis.

Keywords: Cancer; Mucositis; Burrowing; 5-Fluorouracil; Almond

Core tip: In spite of their procyanadin content and anti-oxidant capacity the almond extracts tested failed to provide any ameliorating effect on chemotherapy-induced mucositis in rats as determined through biochemical and histological evaluation. Currently studies utilising animal models of gastrointestinal disease largely fail to assess measures of patient affect. In order to achieve successful translational outcomes assessment of patient experience is important since these disease conditions are often self-limiting. Burrowing behaviour shows promise as a novel measure of affective state in studies of chemotherapy-induced mucositis.