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©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
Rhubarb extract partially improves mucosal integrity in chemotherapy-induced intestinal mucositis
Juliana E Bajic, Georgina L Eden, Lorrinne S Lampton, Ker Y Cheah, Kerry A Lymn, Jinxin V Pei, Andrea J Yool, Gordon S Howarth
Juliana E Bajic, Jinxin V Pei, Andrea J Yool, Gordon S Howarth, Discipline of Physiology, Faculty of Health Sciences, School of Medicine, The University of Adelaide, Adelaide 5005, Australia
Georgina L Eden, Lorrinne S Lampton, Kerry A Lymn, School of Animal and Veterinary Sciences, The University of Adelaide, Roseworthy Campus 5371, Australia
Ker Y Cheah, Gastroenterology Department, Women’s and Children’s Hospital, North Adelaide 5006, Australia
Kerry A Lymn, 2nd Gastroenterology Department, Women’s and Children’s Hospital, North Adelaide 5006, Australia
Gordon S Howarth, 2nd School of Animal and Veterinary Sciences, The University of Adelaide, Roseworthy Campus 5371, Australia
Gordon S Howarth, 3rd Gastroenterology Department, Women’s and Children’s Hospital, North Adelaide 5006, Australia
Gordon S Howarth, 4th Women’s and Children’s Health Research Institute, Women’s and Children’s Hospital, North Adelaide 5006, Australia
Author contributions: Eden GL and Lampton LS contributed equally to this work; Yool AJ and Howarth GS designed the research; Bajic JE, Eden GL, Lampton LS, Cheah KY and Lymn KA performed the research; Pei JV and Yool AJ contributed ex vivo tools; Eden GL, Lampton LS and Howarth GS analysed the data; Bajic JE, Eden GL and Howarth GS wrote the paper.
Institutional review board statement: This collaborative project was a joint venture between The University of Adelaide, Flinders University, UniSA and the Cancer Council SA. 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. The use of animals for teaching, research or experimentation is regulated by State legislation - the South Australian Animal Welfare Act 1985. Internal approval for this study was obtained from the AEC (approval number: S-2010-111).
Institutional animal care and use committee statement: All animal experimentation was approved by the AEC of the University of Adelaide (approval number: S-2010-111) and complied with the National Health and Medical Research Council Code of Practice for Animal Care in Research and Teaching.
Conflict-of-interest statement: The authors wish to acknowledge no conflict of interest.
Data sharing statement: There are no additional data available in relation to this manuscript.
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: Juliana E Bajic, BHSc (Hons), Discipline of Physiology, Faculty of Health Sciences, School of Medicine, The University of Adelaide, Frome Road, Adelaide 5005, Australia.
juliana.bajic@adelaide.edu.au
Telephone: +61-8- 83137591 Fax: +61-8-83133788
Received: April 11, 2016
Peer-review started: April 13, 2016
First decision: June 20, 2016
Revised: July 7, 2016
Accepted: August 8, 2016
Article in press: August 8, 2016
Published online: October 7, 2016
Processing time: 172 Days and 7.9 Hours
AIM
To investigate the effects of orally gavaged aqueous rhubarb extract (RE) on 5-fluorouracil (5-FU)-induced intestinal mucositis in rats.
METHODS
Female Dark Agouti rats (n = 8/group) were gavaged daily (1 mL) with water, high-dose RE (HDR; 200 mg/kg) or low-dose RE (LDR; 20mg/kg) for eight days. Intestinal mucositis was induced (day 5) with 5-FU (150 mg/kg) via intraperitoneal injection. Intestinal tissue samples were collected for myeloperoxidase (MPO) activity and histological examination. Xenopus oocytes expressing aquaporin 4 water channels were prepared to examine the effect of aqueous RE on cell volume, indicating a potential mechanism responsible for modulating net fluid absorption and secretion in the gastrointestinal tract. Statistical significance was assumed at P < 0.05 by one-way ANOVA.
RESULTS
Bodyweight was significantly reduced in rats administered 5-FU compared to healthy controls (P < 0.01). Rats administered 5-FU significantly increased intestinal MPO levels (≥ 307%; P < 0.001), compared to healthy controls. However, LDR attenuated this effect in 5-FU treated rats, significantly decreasing ileal MPO activity (by 45%; P < 0.05), as compared to 5-FU controls. 5-FU significantly reduced intestinal mucosal thickness (by ≥ 29% P < 0.001) as compared to healthy controls. LDR significantly increased ileal mucosal thickness in 5-FU treated rats (19%; P < 0.05) relative to 5-FU controls. In xenopus oocytes expressing AQP4 water channels, RE selectively blocked water influx into the cell, induced by a decrease in external osmotic pressure. As water efflux was unaltered by the presence of extracellular RE, the directional flow of water across the epithelial barrier, in the presence of extracellular RE, indicated that RE may alleviate water loss across the epithelial barrier and promote intestinal health in chemotherapy-induced intestinal mucositis.
CONCLUSION
In summary, low dose RE improves selected parameters of mucosal integrity and reduces ileal inflammation, manifesting from 5-FU-induced intestinal mucositis.
Core tip: Aqueous rhubarb extract partially improved selected parameters of 5-fluorouracil (5-FU)-induced intestinal mucositis in rats. Exposure to 5-FU decreased bodyweight, yet high-dose rhubarb extract (RE) and low-dose RE (LDR) showed no changes. Myeloperoxidase activity was significantly decreased in rats treated with LDR and 5-FU when compared to the intestinal mucositis control group. Ileal mucosal thickness was significantly improved (19%) in animals with intestinal mucositis and treated with LDR. In xenopus oocytes expressing AQP4 water channels, RE blocked swelling induced by a decrease in external osmotic pressure which indicated that water influx across the epithelial barrier was selectively blocked by RE.
