Emu oil reduces small intestinal inflammation in the absence of clinical improvement in a rat model of Indomethacin-induced enteropathy

Extent: 10 p.Nonsteroidal-anti-inflammatory-drug (NSAID) enteropathy is characterized by small intestinal damage and ulceration. Emu Oil (EO) has previously been reported to reduce intestinal inflammation. AIM: We investigated EO for its potential to attenuate NSAID enteropathy in rats. METHODS: Male Sprague Dawley rats (/group) were gavaged with Water, Olive Oil (OO), or EO (0.5 mL; days 0–12) and with 0.5mL Water or the NSAID, Indomethacin (8mg/kg; days 5–12) daily. Disease activity index (DAI), 13C sucrose breath test (SBT), organ weights, intestinal damage severity (IDS), and myeloperoxidase (MPO) activity were assessed. was considered significant. RESULTS. In Indomethacin-treated rats, DAI was elevated (days 10–12) and SBT values (56%) and thymus weight (55%)were decreased, relative tonormal controls. Indomethacin increased duodenum(68%), colon(24%), SI (48%), caecum(48%), liver (51%) and spleen (88%)weights, IDS scores, and MPO levels (jejunum: 195%, ileum: 104%) compared to normal controls. Jejunal MPO levels were decreased (64%) by both EO and OO, although only EO decreased ileal MPO (50%), compared to Indomethacin controls. CONCLUSIONS: EO reduced acute intestinal inflammation, whereas other parameters of Indomethacin induced intestinal injury were not affected significantly. Increased EO dose and/or frequency of administration could potentially improve clinical efficacy.Suzanne M. Abimosleh, Cuong D. Tran and Gordon S. Howart

Grape seed extract reduces the severity of selected disease markers in the proximal colon of dextran sulphate sodium-induced colitis in rats

BackgroundGrape seed extract (GSE) constitutes a rich source of procyanidins. GSE has been demonstrated to exert encouraging anti-inflammatory and anti-ulcer properties in experimental settings, although its effects on inflammation of the colon remain undefined.AimTo determine the effects of GSE in a rat model of dextran sulphate sodium (DSS) for ulcerative colitis.MethodsMale Sprague-Dawley rats were gavaged daily (days 0-10) with GSE (400 mg/kg). Ulcerative colitis was induced by substituting DSS (2 % w/v) for drinking water from days 5-10. A sucrose breath test was performed on day 11 to determine small bowel function and intestinal tissues were collected for histological analyses. Statistical analysis was by one-way or repeated-measures ANOVA and p ResultsCompared to DSS-treated controls, GSE significantly decreased ileal villus height (14 %; p ConclusionsGSE decreased the severity of selected markers of DSS-induced colitis in the distal ileum and proximal colon, suggesting the potential as an adjuvant therapy for the treatment of ulcerative colitis. Future studies of GSE should investigate alternative delivery methods and treatment regimens, further seeking to identify the individual bioactive factors.Ker Y. Cheah, Susan E. P. Bastian, Thomas M. V. Acott, Suzanne M. Abimosleh, Kerry A. Lymn, Gordon S. Howart

Emu oil expedites small intestinal repair following 5-fluorouracil-induced mucositis in rats

Mucositis resulting from cancer chemotherapy is characterized by intestinal inflammation and ulceration. Previously, emu oil (EO) improved intestinal architecture (Br J Nutr, 2010) in a rat model of chemotherapy-induced mucositis. We investigated EO for its further potential to promote intestinal repair in this mucositis model. Female Dark Agouti rats (n = 8/group) were gavaged with water, olive oil (OO) or EO once daily (1 mL), injected with 5-fluorouracil (5-FU) or saline on day 5 and euthanized on day 8, 9, 10 or 11. Intestinal villus height (VH) and crypt depth (CD), neutral mucin-secreting goblet cell (GC) count, myeloperoxidase (MPO) activity and selected cytokines were quantified; P < 0.05 was considered significant. In 5-FU-injected rats, only EO administration significantly increased VH in the ileum (day 8), jejunum and jejunum–ileum junction (days 8 and 9) compared to 5-FU controls (P < 0.05). GC count was significantly reduced by 5-FU (jejunum: days 8 and 9; ileum: day 8; P < 0.05) and EO increased ileal GC on days 10 and 11 compared to 5-FU controls. MPO activity was significantly increased in jejunum (days 8 and 9) and ileum (day 8) following 5-FU injection, compared to normal controls (P < 0.05). Both EO and OO significantly reduced jejunal MPO on days 8 and 9; however, only EO decreased ileal MPO on day 8. Cytokine levels were not significantly affected by either oil or 5-FU administration at the day 8 time point. Promotion of repair from injury could represent a new mechanism of action for EO, suggesting potential as an adjunct to conventional treatment approaches for cancer management.Suzanne Mashtoub, Cuong D Tran and Gordon S Howart

Safety of emu oil for intestinal applications

Basic Science LuminalS Mashtoub, KY Cheah, NLCLansdown, GS Howart

Ostrich oil failed to improve intestinal barrier function following 5-fluorouracil-induced mucositis in rats

Basic Science LuminalMucositis is characterized by intestinal barrier disruption following chemotherapy. Emu Oil promoted small intestinal repair in a rat model of mucositis (Mashtoub, 2013). However, the effects of Ostrich Oil (OO) remain unexplored. We investigated the effects of OO on mucin-secreting goblet cells (GC) during the recovery phase of mucositis. METHODS. Female Dark Agouti rats were allocated to groups (n=8/group): Saline+Water; Saline+OO; 5-Fluorouracil (5-FU)+Water; 5-FU+OO. Mucositis was induced on day 5 by 5-FU injection and rats were euthanized on day 10. Intestinal villus height (VH), crypt depth (CD) and GC were quantified. p<0.05 was considered significant. RESULTS. Compared to water controls, VH was increased 15% by OO (p<0.05), however, VH was unaffected by 5-FU. 5-FU tended to decrease GC count in the villi, relative to water controls (p=0.069). GC count was unaffected by OO in 5-FU-treated rats compared to 5-FU controls. CD was increased 24% by 5-FU (p<0.01); an effect that was not altered by OO. 5-FU reduced GC count in crypts (33%; p<0.01) compared to water controls. However, OO did not attenuate the decrease in GC count in 5-FU-treated rats. CONCLUSIONS. Ostrich Oil treatment failed to improve intestinal barrier function indicated by mucin-secreting goblet cells. As this is the first report of Ostrich Oil in bowel disease, further studies are required to explore dosage and timing regimens.Ker Cheah, Suzanne Mashtoub, and Gordon Howart

Ostrich oil failed to improve intestinal barrier function following 5-fluorouracil-induced mucositis in rats

Basic Science LuminalKY Cheah, S Mashtoub, GS Howart

Emu Oil: A novel therapeutic for disorders of the gastrointestinal tract?

Gastrointestinal diseases characterized by inflammation, including the inflammatory bowel diseases, chemotherapy-induced mucositis and non-steroidal anti-inflammatory drug-induced enteropathy, currently have variably effective treatment options, highlighting the need for novel therapeutic approaches. Recently, naturally-sourced agents including prebiotics, probiotics, plant-extracts and marine-derived oils known to possess anti-inflammatory and anti-oxidant properties have been investigated in vitro and in vivo. However, animal-derived oils are yet to be extensively tested. Emu Oil is extracted from the subcutaneous and retroperitoneal fat of the Emu, a flightless bird native to Australia, and predominantly comprises fatty acids. Despite the limited rigorous scientific studies conducted to date, with largely anecdotal claims, Emu Oil, when administered topically and orally, has been shown to possess significant anti-inflammatory properties in vivo. These include a CD-1 mouse model of croton oil-induced auricular inflammation, experimentally-induced polyarthritis and dextran sulfate sodium-induced colitis. Recently, Emu Oil has been demonstrated to endow partial protection against chemotherapy-induced mucositis, with early indications of improved intestinal repair. Emu Oil could therefore form the basis of an adjunct to conventional treatment approaches for inflammatory disorders affecting the gastrointestinal system.Suzanne M Abimosleh, Cuong D Tran and Gordon S Howart

Emu oil and grape seed extract reduce tumour burden and disease parameters in murine colitis-associated colorectal cancer

Ulcerative colitis (UC) is an incurable condition whereby patients are at an increased risk of developing colorectal cancer (CRC). We aimed to investigate the combination of Emu Oil and grape seed extract (GSE) in an azoxymethane (AOM)/dextran sulphate sodium (DSS) model of colitis-associated CRC (CA-CRC). C57BL/6 mice (n=10/group) were injected i.p. with saline or AOM (7.4mg/kg) and underwent three DSS/water cycles. Mice were orally-gavaged thrice weekly with water (80μL), EO (80μL), GSE (80μL; 400mg/kg) or combined EO/GSE (160μL). Mice were euthanized on day 63. AOM/DSS induced significant bodyweight loss (max -21%) and increased DAI (max +83%) throughout the trial (p<0.05). EO (max -53%), GSE (max -51%) and EO/GSE (max -71%) reduced DAI scores in AOM/DSS mice in all DSS cycles (p<0.05). EO/GSE-treatment in AOM/DSS mice resulted in further DAI reduction compared to EO (max -62%) and GSE (max -71%) alone (p<0.05). AOM/DSS mice presented with severe colonoscopically-assessed colitis at all time-points, which was reduced by EO, GSE and EO/GSE (p<0.05). EO, GSE and EO/GSE reduced the number of colonic tumours compared to AOM/DSS controls (p<0.05). Myeloperoxidase (acute inflammation) and FITC-dextran levels (intestinal permeability) were increased in AOM/DSS controls (p<0.05). EO (-58%) and EO/GSE (-77%) reduced FITC-dextran compared to AOM/DSS controls (p<0.05), with no effect on MPO. Histologically-assessed severity scores were increased in the distal colon of AOM/DSS mice compared to saline (p<0.05), with no effect observed following treatment. The combination of EO and GSE improved clinical indicators and reduced colonic tumours in AOM/DSS treated mice, suggesting potential in CA-CRC management.Lauren C.Chartier, Gordon S.Howarth, Debbie Trinder and Suzanne Mashtou