Effects of Indomethacin on the Duodenal Mucosa of Rats: Comparative Study with Cysteamine

Abstract

Effects of indomethacin and cysteamine on the duodenal mucosa of rats were studied microscopically (using scanning electron microscopy) and also functionally. Indomethacin (5 mg/kg, s.c.) induced no microscopic damage to the duodenal epithelium for up to 6 hr after administration. Indomethacin had no effects on gastric H⁺ output and the amount of H⁺ in the duodenum, but did reduce the duodenal HCO₃^- secretion (both basal and 10 mM-HCl stimulated). PGE₂ contents in the duodenal mucosa were markedly reduced by indomethacin for 6 hr. These results suggest that reductions of duodenal HCO₃^- secretion and endogenous prostaglandins per se do not impair the H⁺ disposal system of the duodenum and so do not damage the epithelial cells. In contrast, cysteamine (100 mg/kg, s.c.) produced microscopic damage to the duodenal epithelium as early as 2 hr later. Cysteamine significantly increased gastric H⁺ output and reduced duodenal HCO₃^-secretion, resulting in an increased amount of H⁺ in the duodenum 3 hr later. Cysteamine had no effect on PGE₂ contents in the duodenum. The time lag between damage formation and functional changes suggests that the earliest damage caused by cysteamine occurs by mechanisms other than erosive action of H⁺ emptied by the stomach. The increased amount of H⁺ may contribute to an enhancement of the initial damage.