Irinotecan-induced mucositis is associated with variation in the expression of regulatory compounds associated with goblet cells

Alimentary mucositis (AM) is a common side effect of antineoplastic treatment and a key reason for cessation of treatment, compromising the chance of remission. Gastrointestinal mucin secretion is associated with regulatory compounds nitric oxide and its respective synthases inducible, epithelial and neural nitric oxide synthase (iNOS, eNOS and nNOS, respectively), vasoactive intestinal polypeptide (VIP), and prostaglandin E2 (PGE2). Changes in secretion during mucositis have been demonstrated in numerous studies, however no secretory regulatory signals have been associated in mucositis induced secretory change. The aim of this study is to investigate regulator factors in the gastrointestinal tract involved in mucin secretion, VIP, NOS, and PGE2, which are suspected of being involved in mucositis, specifically through alteration of neural or goblet cells. Tumour-bearing Dark Agouti rats received a single dose of 175 mg/kg of irinotecan (i.p.) and 0.01mg/kg atropine. (s.c.). Rats were killed post treatment at 6, 24, 48, 72, 96 and 120 hours. Samples were collected, immunohistochemistry and real time PCR were performed to analyse the expression of iNOS, eNOS, nNOS, VIP, and PGE2. Following irinotecan treatment, staining intensity for iNOS positive goblet cells in the crypts of the jejunum decreased significantly at 48 h (p < 0.05). VIP, and PGE2 positive goblet cell numbers showed no change. mRNA expression in iNOS, eNOS, and nNOS showed no change. Irinotecan-induced mucositis is associated with altered secretory regulatory compounds; this may affect mucin secretion increasing the severity of irinotecan induced mucositis.