title: Rhubarb extract partially improves mucosal integrity in chemotherapy-induced intestinal mucositis.
abstract: OBJECTIVE
  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)viaintraperitoneal 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 atP< 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.
  
  
  CONCLUSIONS
  In summary, low dose RE improves selected parameters of mucosal integrity and reduces ileal inflammation, manifesting from 5-FU-induced intestinal mucositis.
authors.affiliation: 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.
authors.forename: Juliana E
authors.initials: JE
authors.lastname: Bajic
authors.affiliation: 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.
authors.forename: Georgina L
authors.initials: GL
authors.lastname: Eden
authors.affiliation: 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.
authors.forename: Lorrinne S
authors.initials: LS
authors.lastname: Lampton
authors.affiliation: 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.
authors.forename: Ker Y
authors.initials: KY
authors.lastname: Cheah
authors.affiliation: 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.
authors.forename: Kerry A
authors.initials: KA
authors.lastname: Lymn
authors.affiliation: 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.
authors.forename: Jinxin V
authors.initials: JV
authors.lastname: Pei
authors.affiliation: 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.
authors.forename: Andrea J
authors.initials: AJ
authors.lastname: Yool
authors.affiliation: 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.
authors.forename: Gordon S
authors.initials: GS
authors.lastname: Howarth
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D051401:Aquaporin 4 / Q000378:metabolism; D001835:Body Weight; D005243:Feces; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects*; D007249:Inflammation / Q000473:pathology; D007413:Intestinal Mucosa / Q000473:pathology / Q000503:physiopathology*; D052016:Mucositis / Q000503:physiopathology*; D009865:Oocytes / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry*; D051381:Rats; D012250:Rheum / Q000737:chemistry*; D014981:Xenopus
chemical_list: D000970:Antineoplastic Agents; C496032:Aqp4 protein, rat; D051401:Aquaporin 4; D010936:Plant Extracts; D009195:Peroxidase; D005472:Fluorouracil
keywords: Fluorouracil; Inflammation; Mucositis; Rats; Rheum