Background: Mucositis is a severe does limiting toxic side effect of chemotherapy. Irinotecan, used to treat solid tumours, is associated with severe mucositis and diarrhoea. Mucus secretion may be associated with incidence and severity of diarrhoea. The aim of this study was to determine the changes to mucins in the gastrointestinal tract during mucositis.
Methods: Dark Agouti (DA) rats were administered a single dose of 175 mg/kg of irinotecan intraperitoneally (ip) and 0.01mg/kg atropine subcutaneously (sc). Experimental and untreated control rats were killed at times 6, 24, 48, 72, 96 and 120 h after treatment. Jejunum and colon samples were formalin fixed. Haematoxylin and eosin (H&E) staining, Alcian Blue-PAS staining, High iIron dDiamine and immunohistochemistry with Muc2 and Muc4 antibodies were carried out. Goblet cells (intact and cavitated) and positively stained cells were counted. Statistical analyses were carried out using a Kruskal-Wallis test with Dunns post test.
Results: Cavitated goblet cells (cells which have undergone recent exocytosis of mucin stores) as a percentage of the total cells increased significantly (p>0.05) at 72h compared with controls in the colon. Muc2 positively stained goblet cells in the crypts in the jejunum significantly decreased (p>0.05) at 96h, and in the colon at 72h compared to controls. Muc4 positively stained cells in the colon decreased significantly at 72h, 96h and 120h (p>0.05) compared to controls.
Conclusions: Exocytosis of mucin stores increases following administration of irinotecan. Muc2 and Muc4 expression is also increased at similar time points. This indicates that Muc 2 and Muc 4 expression are associated with the exocytosis of mucins, which is likely to contribute to the pathophysiology of mucositis and associated diarrhoea.