The new selective glp-2 receptor agonist, elsiglutide, improves irinotecan-induced diarrhoea and mucositis in the rat

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dc.contributor.authorMayo, B.
dc.contributor.authorBateman, E.
dc.contributor.authorStringer, A.
dc.contributor.authorPlews, E.
dc.contributor.authorWignall, A.
dc.contributor.authorWozniak, B.
dc.contributor.authorWhite, I.
dc.contributor.authorPietra, C.
dc.contributor.authorCantoreggi, S.
dc.contributor.authorKeefe, D.
dc.contributor.conferenceCOSA's 41st Annual Scientific Meeting. Joining Forces - Accelerating Progress (2 Dec 2014 - 4 Dec 2014 : Melbourne, Vic.)
dc.date.issued2014
dc.description.abstractIntroduction: Irinotecan is a common chemotherapeutic agent that's use is associated with severe gastrointestinal mucositis presenting as diarrhoea, nausea, vomiting, and pain and ulceration of the digestive tract. Elsiglutide, a glucagon-like peptide-2 receptor agonist, has recently been shown to decrease diarrhoea and gastrointestinal (GI) damage caused by irinotecan administration in a rat model. Interestingly, the trialled doses showed that 0.9 mg/kg/day (subcutaneous, 5 days) was more effective than 1.8 mg/kg (subcutaneous, 5 days) of elsiglutide, suggesting a bell-shape dose response. Objectives: To test whether a decreased dose of 0.45 mg/kg of elsiglutide further improves the GI toxicity associated with irinotecan in the rat model of irinotecan-induced mucositis. Method: Dark Agouti rat model of irinotecan-induced mucositis was used to characterise effects of lower dose elsiglutide on irinotecan-induced diarrhoea and GI damage. Animals received 200 mg/kg at 0 hours intraperitoneal irinotecan, and daily subcutaneous dosing of 0.45 mg/kg elsiglutide for 5 days, then were killed at 6, 72 or 120 hours post-chemotherapy (n = 6). Jejunum and ileum were taken for histology and microdissection. Results: Elsiglutide reduced duration of severe diarrhoea. Small intestinal wet weight increased significantly (grams, p < 0.05) following elsiglutide with irinotecan (3.75 +/- 0.12 g at 72 hrs, 7.64 +/- 0.33 g at 120 hrs) compared with irinotecan alone (3.21 +/- 0.07 g at 72 hrs, 6.39 +/- 0.39 g at 120 hrs). Villous blunting, crypt ablation and enterocyte disruption improved and inflammatory infiltrate decreased following elsiglutide and irinotecan compared with irinotecan alone. Villous area significantly increased (mm2, p < 0.05) at 72 hrs following elsiglutide with irinotecan (Jejunum 0.061 +/- 0.004; Ileum 0.042 +/- 0.003) when compared with irinotecan alone (Jejunum 0.042 +/- 0.005; Ileum 0.03 +/- 0.004). Conclusions: Elsiglutide 0.45 mg/kg/day following irinotecan administration may protect against and reduce damage to the small intestine. However, this data suggests the overall effect of 0.45 mg/kg/day may be lower than that in previous experiments using 0.9 mg/kg/day, but is still significant. Additional studies are required to explain the variations and to explore a range of effective doses.
dc.description.statementofresponsibilityBronwen Mayo, Emma Bateman, Andrea Stringer, Erin Plews, Anthony Wignall, Belinda Wozniak, Imogen White, Claudio Pietra, Sergio Cantoreggi, Dorothy Keefe
dc.identifier.citationAsia Pacific Journal of Clinical Oncology, 2014, vol.10, iss.Suppl. 8, pp.134-134
dc.identifier.doi10.1111/ajco.12305
dc.identifier.issn1743-7555
dc.identifier.issn1743-7563
dc.identifier.orcidBateman, E. [0000-0003-1665-102X]
dc.identifier.orcidStringer, A. [0000-0003-3245-5360]
dc.identifier.orcidWhite, I. [0000-0002-9629-9064]
dc.identifier.orcidKeefe, D. [0000-0001-9377-431X]
dc.identifier.urihttp://hdl.handle.net/2440/91357
dc.language.isoen
dc.publisherWiley
dc.rights© 2014 The Authors. Asia-Pacific Journal of Clinical Oncology © 2014 Wiley Publishing Asia Pty Ltd
dc.titleThe new selective glp-2 receptor agonist, elsiglutide, improves irinotecan-induced diarrhoea and mucositis in the rat
dc.typeConference item
pubs.publication-statusPublished

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