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

Juliana E. Bajic, Georgina Eden, Lorrinne S. Lampton, Ker Y. Cheah, Kerry A. Lymn, Jinxin V. Pei, Andrea J. Yool, Gordon S. Howarth

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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.

LanguageEnglish
Pages8322-8333
Number of pages12
JournalWorld Journal of Gastroenterology
Volume22
Issue number37
DOIs
Publication statusPublished - 7 Oct 2016

Keywords

  • Fluorouracil
  • Inflammation
  • Mucositis
  • Rats
  • Rheum

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Bajic, Juliana E. ; Eden, Georgina ; Lampton, Lorrinne S. ; Cheah, Ker Y. ; Lymn, Kerry A. ; Pei, Jinxin V. ; Yool, Andrea J. ; Howarth, Gordon S. / Rhubarb extract partially improves mucosal integrity in chemotherapy-induced intestinal mucositis. In: World Journal of Gastroenterology. 2016 ; Vol. 22, No. 37. pp. 8322-8333.
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title = "Rhubarb extract partially improves mucosal integrity in chemotherapy-induced intestinal mucositis",
abstract = "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.",
keywords = "Fluorouracil, Inflammation, Mucositis, Rats, Rheum",
author = "Bajic, {Juliana E.} and Georgina Eden and Lampton, {Lorrinne S.} and Cheah, {Ker Y.} and Lymn, {Kerry A.} and Pei, {Jinxin V.} and Yool, {Andrea J.} and Howarth, {Gordon S.}",
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Bajic, JE, Eden, G, Lampton, LS, Cheah, KY, Lymn, KA, Pei, JV, Yool, AJ & Howarth, GS 2016, 'Rhubarb extract partially improves mucosal integrity in chemotherapy-induced intestinal mucositis', World Journal of Gastroenterology, vol. 22, no. 37, pp. 8322-8333. https://doi.org/10.3748/wjg.v22.i37.8322

Rhubarb extract partially improves mucosal integrity in chemotherapy-induced intestinal mucositis. / Bajic, Juliana E.; Eden, Georgina; Lampton, Lorrinne S.; Cheah, Ker Y.; Lymn, Kerry A.; Pei, Jinxin V.; Yool, Andrea J.; Howarth, Gordon S.

In: World Journal of Gastroenterology, Vol. 22, No. 37, 07.10.2016, p. 8322-8333.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Rhubarb extract partially improves mucosal integrity in chemotherapy-induced intestinal mucositis

AU - Bajic, Juliana E.

AU - Eden, Georgina

AU - Lampton, Lorrinne S.

AU - Cheah, Ker Y.

AU - Lymn, Kerry A.

AU - Pei, Jinxin V.

AU - Yool, Andrea J.

AU - Howarth, Gordon S.

PY - 2016/10/7

Y1 - 2016/10/7

N2 - 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.

AB - 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.

KW - Fluorouracil

KW - Inflammation

KW - Mucositis

KW - Rats

KW - Rheum

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U2 - 10.3748/wjg.v22.i37.8322

DO - 10.3748/wjg.v22.i37.8322

M3 - Article

VL - 22

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EP - 8333

JO - World Journal of Gastroenterology

T2 - World Journal of Gastroenterology

JF - World Journal of Gastroenterology

SN - 1007-9327

IS - 37

ER -