Emu Oil Improves Clinical Indicators of Disease in a Mouse Model of Colitis-Associated Colorectal Cancer

Chartier, Lauren C.; Howarth, Gordon S.; Lawrance, Ian C.; Trinder, Debbie; Barker, Scott J.; Mashtoub, Suzanne

doi:10.1007/s10620-017-4876-4

Cited by 23 publications

(17 citation statements)

References 23 publications

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“…Myeloperoxidase assay (MPO) was performed to detect neutrophil infiltration using protocols previously published 51 . Briefly, distal colon tissue was homogenized and centrifuged at 13,000 g for 12 min, supernatant was discarded and 0.5% hexadecyltrimethyl ammonium bromide buffer (Sigma Aldrich, NSW, AUS) was used to re-suspend the tissue homogenate.…”

Section: Methodsmentioning

confidence: 99%

Flightless I exacerbation of inflammatory responses contributes to increased colonic damage in a mouse model of dextran sulphate sodium-induced ulcerative colitis

Kopecki

Yang

Treloar

et al. 2019

Sci Rep

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Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by cytokine driven inflammation that disrupts the mucosa and impedes intestinal structure and functions. Flightless I (Flii) is an immuno-modulatory protein is a member of the gelsolin family of actin-remodelling proteins that regulates cellular and inflammatory processes critical in tissue repair. Here we investigated its involvement in UC and show that Flii is significantly elevated in colonic tissues of patients with inflammatory bowel disease. Using an acute murine model of colitis, we characterised the contribution of Flii to UC using mice with low ( Flii +/− ), normal ( Flii +/+ ) and high Flii ( Flii Tg/Tg ). High levels of Flii resulted in significantly elevated disease severity index scores, increased rectal bleeding and degree of colon shortening whereas, low Flii expression decreased disease severity, reduced tissue inflammation and improved clinical indicators of UC. Mice with high levels of Flii had significantly increased histological disease severity and elevated mucosal damage with significantly increased inflammatory cell infiltrate and significantly higher levels of TNF-α, IFN-γ, IL-5 and IL-13 pro-inflammatory cytokines. Additionally, Flii overexpression resulted in decreased β-catenin levels, inhibited Wnt/β-catenin signalling and impaired regeneration of colonic crypts. These studies suggest that high levels of Flii, as is observed in patients with UC, may adversely affect mucosal healing via mechanisms involving Th 1 and Th 2 mediated tissue inflammation and Wnt/β-catenin signalling pathway.

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Section: Methodsmentioning

confidence: 99%

Flightless I exacerbation of inflammatory responses contributes to increased colonic damage in a mouse model of dextran sulphate sodium-induced ulcerative colitis

Kopecki

Yang

Treloar

et al. 2019

Sci Rep

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“…The ARC undertakes a quarterly health screening, covering various bacterial, viral and parasitic organisms, all of which the obtained colony screened negative for. Only female mice were used to remain consistent with data obtained from previous studies [13,14]. Environment was regulated at 21-24˚C with 42-44% humidity and a light/dark cycle of 14:10 h. Mice were fed standard mouse chow (meat free mouse diet; Specialty Feeds, Glen Forrest, Western Australia) and provided with enrichment items including shredded paper, polycarbonate 'houses' and cardboard toilet paper rolls for the duration of the trial.…”

Section: Animal Studiesmentioning

confidence: 99%

Affective state determination in a mouse model of colitis-associated colorectal cancer

et al. 2020

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Behavioural indicators of affective state, including burrowing, clinical scores and the Mouse Grimace Score have not yet been validated in mouse models of chronic gastrointestinal disease. Additionally, a comparison of these methods has not been characterised. This study aimed to determine which behavioural assessment was the optimal indicator of disease, evidenced by correlation with clinically-assessed measures, in an azoxymethane (AOM)/dextran sulphate sodium (DSS) mouse model of colitis-associated colorectal cancer. C57BL/6 mice were allocated to four groups (n = 10/group); 1) saline control, 2) saline+buprenorphine, 3) AOM+DSS+water, 4) AOM+DSS+buprenorphine. Mice were gavaged thrice weekly with water or buprenorphine (0.5mg/kg; 80μL) for 9 weeks. Disease activity index (DAI) was measured daily; burrowing and grimace analyses occurred on days-1, 5, 19, 26, 40, 47 and 61. Colonoscopies were performed on days 20, 41 and 62. All animals were euthanized on day 63. Burrowing activity and retrospective grimace analyses were unaffected (P>0.05), whilst DAI was significantly increased (P<0.05) in mice with colitis-associated colorectal cancer compared to normal controls. In addition, DAI was positively correlated with colonoscopically-assessed severity and tumour number (P<0.05). We conclude that traditional measures of DAI or clinical scoring provide the most reliable assessment of wellbeing in mice with colitis-associated colorectal cancer.

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“…colitis-associated colorectal cancer. 14 The mode of Emu Oil action is yet to be fully elucidated; however, its growth stimulatory properties and therapeutic efficacy may be attributed to its fatty acid composition, their ratios and components within the non-triglyceride fraction, including skin permeation enhancing factors and antioxidants. Despite similar mucosal growth stimulatory effects of both Emu Oil and olive oil in the current study, the differing compositions of the two oils may have been responsible for the superior therapeutic efficacy of Emu Oil demonstrated in previous pre-clinical studies of different bowel disorders.…”

Section: Discussionmentioning

confidence: 99%

Intestinal homeostasis is restored in mice following a period of intestinal growth induced by orally administered Emu Oil

Mashtoub

Cheah

Lymn

et al. 2018

Exp Biol Med (Maywood)

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Previously, we reported that orally administered Emu Oil (EO) increases mucosal thickness in the small intestine and colon in rodent models of chemotherapy-induced mucositis and colitis. However, it remains unclear whether mucosal thickening (crypt and villus lengthening) represents a process of normal or aberrant growth. We sought to determine if villus height (VH) and crypt depth (CD) measurements returned to normal in EO-treated rats following withdrawal of EO therapy. Dark agouti rats ( n = 8/group) were gavaged daily for 10 days with water, olive oil (OO), or EO (0.5 mL or 1 mL). Groups of rats were euthanized on days 10 and 17. Intestinal weights, lengths, VH, and CD were quantified. P < 0.05 was considered significant. On day 10, jejuno-ileum weight was increased by OO (26%) and EO (0.5 mL: 15%; 1 mL: 29%) compared to water controls ( P < 0.01), which was normalized by day 17. On days 10 and 17, jejuno-ileum length was greater in OO- (12%) and EO-treated rats (0.5 mL: 8%; 1 mL: 12%; P < 0.05), relative to water controls. On day 10, OO and EO increased ileal VH (OO: 32%; 0.5 EO: 22%; EO: 35%; P < 0.01) and CD (OO: 17%; 0.5 EO: 13%; EO: 22%) compared to water controls. Importantly, however, after withdrawal of all oils, VH and CD measurements returned to normal control values. Moreover, the VH:CD ratio (potential indicator of dysplasia) remained unchanged in all experimental groups on days 10 and 17. The restoration of normal intestinal architecture following cessation of Emu Oil therapy supports its safety for application in intestinal disorders. Impact statement Uncontrolled inflammation and intestinal proliferation can predispose to the development of colorectal cancer. In previous pre-clinical studies, we demonstrated that oral administration of Emu Oil promotes intestinal repair via stimulation of the mucosa in response to tissue injury and inflammation. Therefore, it was important to determine if Emu Oil administration did not promote the precocious development of colorectal cancer. The current study revealed that Emu Oil returned indicators of intestinal proliferation back to normal values after a period of seven days. These data strongly support the safety of Emu Oil for further studies in the context of bowel inflammation.

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Emu Oil Improves Clinical Indicators of Disease in a Mouse Model of Colitis-Associated Colorectal Cancer

Abstract: Emu Oil improved clinical indicators and reduced severity of colitis-associated colorectal cancer, suggesting therapeutic potential in colitis management.

Cited by 23 publications

References 23 publications

Flightless I exacerbation of inflammatory responses contributes to increased colonic damage in a mouse model of dextran sulphate sodium-induced ulcerative colitis

Flightless I exacerbation of inflammatory responses contributes to increased colonic damage in a mouse model of dextran sulphate sodium-induced ulcerative colitis

Affective state determination in a mouse model of colitis-associated colorectal cancer

Intestinal homeostasis is restored in mice following a period of intestinal growth induced by orally administered Emu Oil

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