Published online Oct 7, 2016. doi: 10.3748/wjg.v22.i37.8322
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
To investigate the effects of orally gavaged aqueous rhubarb extract (RE) on 5-fluorouracil (5-FU)-induced intestinal mucositis in rats.
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.
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.
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.