8 Indomethacin and flurbiprofen decrease proportions of acidic goblet cells within the crypts in the distal small intestine in CD-1 mice

Long-term administration of non-steroidal anti-inflammatory drugs (NSAIDs) in patients can lead to the formation of gastroduodenal ulcers. Goblet cells contribute to gastrointestinal mucosal defence by secreting mucins. These mucins have a cytoprotective function in protecting the gastrointestinal tract against damage from agents as diverse as NSAIDs. The possibility that goblet cell behaviour could be affected by NSAID treatment was therefore examined in this study. Small intestinal goblet cell proportions from the distal small intestine were examined following administration of two NSAIDs (indomethacin 1 mg kg−1 i.p., flurbiprofen 1 mg kg−1 i.p.) over 36 h. The small intestine was divided into four segments A, B, C and D. Samples obtained from the distal small intestine (segments C and D) were processed for wax histology and stained with alcian blue and periodic acid schiff (PAS) and examined by light microscopy. The PAS and alcian blue stain was utilized to illustrate goblet cells containing neutral and acidic mucin types, respectively, and counts were made of both cell types. Total numbers of crypt cell profiles were also obtained. The percentage of goblet cells within the crypts was calculated as a proportion of the total number of cryptal cells. The results showed that both mucin types are present in control and treated groups. Neutral mucins were the predominant mucin type in the intestinal crypts in all groups. In intestinal segments C and D, both flurbiprofen and indomethacin significantly decreased the total number of cryptal cells when compared with control values. Neither flurbiprofen nor indomethacin affected the proportions of neutral goblet cells in intestinal segments C and D when compared with control values. Proportions of acidic goblet cells were significantly reduced in both flurbiprofen- and indomethacin-treated groups when compared with controls. Thus the administration of flurbiprofen and indomethacin appears to affect preferentially acidic mucin containing goblet cells, reducing their identification either through differentiation, cell loss or increased secretion; the relationship between acidic and neutral mucin producing goblet cell populations in the distal small intestine, however, remains unaffected. No ulceration was observed in treated specimens; the possibility that higher dosages may produce increasingly significant effects on the goblet cell population cannot be ruled out.