Abstract
Nonsteroidal anti‐inflammatory drugs (NSAIDs) are one of the most commonly used drugs for the alleviation of pain and inflammation. Unfortunately, daily use of NSAIDs is associated with significant adverse side effects, including erosion and ulceration of the gastrointestinal (GI) tract. Previous studies have shown that NSAIDs inhibit migration of IEC‐6 cells (a small intestinal epithelial cell line) by inhibiting calpain activity and membrane expression. The current study was undertaken to determine if NSAIDs affect calpain expression and cell migration in vivo. Rats were treated with indomethacin or NS‐398 for 72 h and injected with bromodeoxyuridine (BrdU) at 6, 12, 18, or 24 h prior to tissue harvest. Sections of duodenum were harvested for RNA and protein extraction as well as for histomorphometric analysis of crypt and villous length and anti‐BrdU immunohistochemistry to estimate cell migration. Our results show that there was stunting of villi and a reduction in cell migration in rat duodenum by NSAID treatment. In addition, protein expression for calpains 1, 2, and 8 was significantly reduced in duodenal mucosa by NSAID treatment despite enhanced expression of calpain 8 mRNA. These results suggest that reductions in calpain expression in vivo are associated with deficits in cell migration caused by NSAIDs, and that calpains may be clinically important targets of NSAID‐induced GI toxicity.Grant Funding Source: Supported by the National Institute of Diabetes and Digestive and Kidney Diseases (1R15DK091791)
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