Rhubarb extract partially improves mucosal integrity in chemotherapy-induced intestinal mucositis

Abstract

AIMTo investigate the effects of orally gavaged aqueous rhubarb extract (RE) on 5-fluorouracil (5-FU)-induced intestinal mucositis in rats.METHODSFemale 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.RESULTSBodyweight 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.CONCLUSIONIn summary, low dose RE improves selected parameters of mucosal integrity and reduces ileal inflammation, manifesting from 5-FU-induced intestinal mucositis.

Aquaporin 4 deficiency alleviates experimental colitis in mice

“…and subsequently showed improved survival (22,23). A recent report showed that aqueous rhubarb extract partially improved intestinal mucositis by blocking basolateral AQP4 channels and increasing net fluid absorption across the intestinal epithelium in the 5-fluorouracilinduced rat enteritis model (24). Although this model did not examine the same organ, the effects of AQP4 on inflammation were consistent with our study.…”

From the Bottom-Up: Chemotherapy and Gut-Brain Axis Dysregulation

“…Although guidelines for the prevention and treatment of mucositis exist, they fail to include effective treatment options (Gibson et al, 2013 ). Novel complementary treatment approaches are showing positive results utilizing naturally sourced products, such as Emu Oil and Rhubarb extract (Mashtoub et al, 2013 ; Bajic et al, 2016a ). Although these treatment strategies show promise, to date they are still in the pre-clinical stages.…”

Ursodeoxycholic acid attenuates 5‑fluorouracil‑induced mucositis in a rat model

“…The present therapy for chemotherapy-associated mucositis mainly consists of topical analgesics, mucosal coating agents, antimicrobials, and cryotherapy (7). Recent studies have reported that chemotherapy-induced mucositis improves with keratinocyte growth factor and rhubarb extract in murine models (6)(7)(8)(9)(10). Current treatment methods for chemotherapy-induced mucositis usually aim to decrease the symptoms, rather than providing a complete cure.…”