No abstract

This is the first study to demonstrate histological and immunohistochemical evidence of changes occurring concurrently in different sites of the AT following chemotherapy. The results of the study provide further evidence for the role of NF-kappaB and associated pro-inflammatory cytokines in the pathobiology of AT mucositis. The presence of these factors in tissues from different sites of the AT also suggests that there may be a common pathway along the entire AT causing mucositis following irinotecan administration.

5-Fluorouracil (5-FU) is a commonly used chemotherapy agent in clinical oncology practice. Two of its major side effects are mucositis and diarrhoea. The structure of mucins offers mucosal protection, and allows maintenance of intestinal flora by providing attachment sites and preventing bacterial overgrowth and/or penetration. The aim of this study was to investigate changes in mucin secretion and microflora following treatment with 5-FU. Female DA rats were given a single 150 mg/ kg i.p. dose of 5-FU. Rats were killed at various time points after treatment. Control rats received no treatment. Jejunum, colon and faecal samples were collected. Standard microbiological culture techniques were used to identify bacteria, and real-time PCR was used to quantify bacteria in faecal samples. Goblet cells and cavitated goblet cells (having undergone mucus exocytosis) were also counted. Statistical analysis was carried out using Kruskal-Wallis test, a non-parametric method of testing equality of group medians. Following treatment with 5-FU, we showed decreases in Clostridium spp., Lactobacillus spp. and Streptococcus spp., and an increase in Escherichia spp. in the jejunum. In the colon, 5-FU caused decreases in Enterococcus spp., Lactobacillus spp. and Streptococcus spp. Real-time PCR of faecal samples showed decreasing trends in Lactobacillus spp. and Bacteroides spp., and an increasing trend in E. coli. Significant increases (P < 0.05) were seen in Clostridium spp. and Staphylococcus spp. at 24 h. Goblet cell numbers decreased significantly in the jejunum from 24-72 h, with a significant increase in the percentage of cavitated goblet cells. In conclusion, 5-FU treatment causes significant changes in intestinal flora and mucin secretion in rats. These changes could result in systemic effects and, in particular, may contribute to the development of chemotherapy-induced mucositis.