Pulmonary, Gastrointestinal and Urogenital PharmacologyZinc protects against indomethacin-induced damage in the rat small intestine

The clinical utility of nonsteroidal anti-inflammatory drugs (NSAIDs) is often limited by the adverse effects that they produce in the small intestine. Alterations in the composition and functions of the glycocalyx and brush border membranes of the rat small intestine have been shown to occur in response to indomethacin, an NSAID often used in the study of adverse effects of these drugs. The micronutrient, zinc, has been documented to have cytoprotective effects in the gastrointestinal tract. The aim of this study was to evaluate the potential of zinc to reduce indomethacin-induced small intestinal damage. We pre-treated rats with zinc sulphate (50 mg/kg body weight) 2 h before administration of indomethacin (20 mg/kg body weight) and sacrificed the rats 1, 12 or 24 h after indomethacin. The extent of small intestinal mucosal damage and the content of lipids and sugars in the mucosa were determined. Bacterial counts in the intestinal lumen and the mucosa were ascertained. Activities of matrix metalloproteinases (MMPs) and levels of metallothionein in the mucosa were also measured. Pre-treatment with zinc sulphate was found to reduce the extent of indomethacin-induced mucosal damage. It also prevented drug-induced changes in the content of lipids and sugars in the mucosa. Drug-induced increases in activities of the MMPs and bacterial counts in the intestine were also attenuated by zinc. Metallothionein levels were significantly higher in animals pre-treated with zinc. We conclude that zinc was effective in protecting against indomethacin-induced small intestinal damage and suggest that it may do so by induction of metallothionein.