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

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

doi:10.3748/wjg.v22.i37.8322

Cited by 20 publications

(23 citation statements)

References 44 publications

(73 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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.…”

Section: Discussionsupporting

confidence: 90%

Aquaporin 4 deficiency alleviates experimental colitis in mice

et al. 2019

View full text Add to dashboard Cite

Aquaporin (AQP) 4 is expressed in the basolateral membrane of colonic epithelial cells, and the purpose of this study was to explore the mechanistic role of AQP4 in experimental colitis. Experimental colitis was induced in AQP4 knockout (AQP4−/−) CD‐1 mice and AQP4 wild‐type (AQP4wt) mice by oral administration of dextran sulfate sodium (DSS). Experimental colitis was clinically established. Compared with AQP4wt mice, AQP4−/− mice showed increased tolerance to DSS‐induced experimental colitis, including lesser degree of weight loss, diarrhea and bleeding, lower disease activity index scores, longer colon lengths, and lesser histologic scores. DSS‐treated AQP4−/− mice had lower serum levels of IL‐6 and TNF, higher IL‐10 level, and lesser inflammatory cell infiltration. DSS‐treated AQP4−/− mice also had lower immunostaining of NF‐κB p65 as well as nuclear levels of p65 and phosphorylated p65. Sequencing of 16S rRNA indicated that DSS‐treated AQP4−/− mice maintained intestinal microbial diversity and had higher Firmicutes/Bacteroidetes ratios and greater relative abundance of Erysipelotrichaceae species. These results suggested for the first time that AQP4 deficiency alleviates experimental colitis in mice. Our study helps to understand the pathogenesis of inflammatory bowel diseases, and blocking AQP4 may represent a novel therapeutic approach for ulcerative colitis.—Wang, L., Tang, H., Wang, C., Hu, Y., Wang, S., Shen, L. Aquaporin 4 deficiency alleviates experimental colitis in mice. FASEB J. 33, 8935–8944 (2019). http://www.fasebj.org

show abstract

Section: Discussionsupporting

confidence: 90%

Aquaporin 4 deficiency alleviates experimental colitis in mice

et al. 2019

View full text Add to dashboard Cite

show abstract

“…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.…”

Section: Chemotherapy From the Bottom-up: The Gut And Cognitionmentioning

confidence: 99%

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

Bajic

Johnston

Howarth

et al. 2018

Front. Behav. Neurosci.

View full text Add to dashboard Cite

The central nervous system and gastrointestinal tract form the primary targets of chemotherapy-induced toxicities. Symptoms associated with damage to these regions have been clinically termed chemotherapy-induced cognitive impairment and mucositis. Whilst extensive literature outlines the complex etiology of each pathology, to date neither chemotherapy-induced side-effect has considered the potential impact of one on the pathogenesis of the other disorder. This is surprising considering the close bidirectional relationship shared between each organ; the gut-brain axis. There are complex multiple pathways linking the gut to the brain and vice versa in both normal physiological function and disease. For instance, psychological and social factors influence motility and digestive function, symptom perception, and behaviors associated with illness and pathological outcomes. On the other hand, visceral pain affects central nociception pathways, mood and behavior. Recent interest highlights the influence of functional gut disorders, such as inflammatory bowel diseases and irritable bowel syndrome in the development of central comorbidities. Gut-brain axis dysfunction and microbiota dysbiosis have served as key portals in understanding the potential mechanisms associated with these functional gut disorders and their effects on cognition. In this review we will present the role gut-brain axis dysregulation plays in the chemotherapy setting, highlighting peripheral-to-central immune signaling mechanisms and their contribution to neuroimmunological changes associated with chemotherapy exposure. Here, we hypothesize that dysregulation of the gut-brain axis plays a major role in the intestinal, psychological and neurological complications following chemotherapy. We pay particular attention to evidence surrounding microbiota dysbiosis, the role of intestinal permeability, damage to nerves of the enteric and peripheral nervous systems and vagal and humoral mediated changes.

show abstract

“…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.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2018

View full text Add to dashboard Cite

Intestinal mucositis is a commonly encountered complication of chemotherapy. However, there are few effective treatments or preventive methods. Ursodeoxycholic acid (UDCA) stabilizes cell membranes, acts as an antioxidant and inhibits apoptosis, thereby exerting cytoprotective effects. The aim of the present study was to examine the ability of UDCA to protecting against chemotherapy-associated mucositis. Sprague-Dawley rats were randomly assigned to five groups: Control, vehicle + 5-fluorouracil (5-FU), 5-FU + UDCA (10 mg/kg/day), 5-FU + UDCA (100 mg/kg/day) and 5-FU + UDCA (500 mg/kg/day). Following randomization, a single dose of 5-FU was injected and varying amounts of UDCA was administered to each group. UDCA was administered orally to rats for 6 days, beginning 1 day prior to 5-FU administration. The rats were sacrificed 1 day following the last UDCA administration and intestinal tissue specimens were prepared for analysis. UDCA administration attenuated body weight loss, decreased inflammatory cytokine levels and curbed intestinal villus damage in the 10 and 100 mg/kg/day groups. When compared with the jejunal villi lengths in the vehicle+5-FU group (212.8±58.0 µm), those in the 5-FU + UDCA (10 mg/kg/day) and 5-FU + UDCA (100 mg/kg/day) groups were significantly greater [331.3±18.0 µm (P=0.001) and 310.0±112.6 µm (P=0.046), respectively]. Tumor necrosis factor-α and interleukin-6 levels were reduced in the 10 and 100 mg/kg/day UDCA groups (P<0.05). UDCA considerably attenuated the elevation in inflammatory cytokines and intestinal villus damage. The results of the study suggest that UDCA may be used as a protective agent against chemotherapy-associated intestinal mucositis.

show abstract

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

Cited by 20 publications

References 44 publications

Aquaporin 4 deficiency alleviates experimental colitis in mice

Aquaporin 4 deficiency alleviates experimental colitis in mice

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

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

Contact Info

Product

Resources

About