Cysteamine-induced Duodenal Ulcer and Acid Secretion in the Rat

Abstract

Duodenal ulcers can be produced in rats within 24 h by a single subcutaneous administration of cysteamine. To determine the role of gastric acid secretion in the pathogenesis of these ulcers, secretory and pathoanatomic studies were performed in chronic fistula rats ater an ulcerogenic dose of cysteamine. A prolonged increase of acid secretion was seen after cysteamine, reaching fourfold the basal level after 5 h. The acid response lasted for 10 to 11 h. After vagotomy cysteamine-induced acid secretion was markedly reduced. Ulcer formation was prevented by vagotomy and by drainage of the gastric juice before it entered the duodenum. When a gastric acid output equivalent to that produced by the ulcerogenic dose of cysteamine was induced by repeated injections of pentagastrin, no mucosal changes were seen in the duodenum. These results indicate that, although some acid in the duodenum is required for ulcer formation, the hypersecretion of acid induced by cysteamine is not the only factor responsible for the development of duodenal ulcer.

The relationship of intraduodenal pH and delayed gastric emptying in duodenal ulceration induced by mepirizole or cysteamine in rats.

“…In contrast to with the low dose, the accumulation of gastric contents in response to the high dose of cysteamine gradually in creased, the maximum being reached at 6 hr. Since a delay in gastric emptying was already evident 1 hr after administration, this gradual accumulation appears to be due to the gradual stimulation of gastric acid secretion, as re ported by other authors (21). The maximal volume and amount of acid with the high dose of cysteamine were almost double those with the high dose of mepirizole.…”

The evaluation and treatment of gastrointestinal disease in children with cystinosis receiving cysteamine

“…4 The dose required, however, is 700 to 1000 mg/kg body weight or 40 to 60 times the per-kilogram body weight dose that is currently administered at any one time for the treatment of cystinosis. 1,[5][6][7] The exact mechanism by which cysteamine induces ulcerogenesis is unclear, but it likely involves gastric acid-hypersecretion 6,18 secondary to hypergastrinemia. 19 Low intraluminal pH will inhibit gastrin release through a negative feedback loop.…”

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

“…This finding is consistent with the observations by other investigators (9) who reported the development of microscopic damage in rat duodenal epithelium 4 to 8 hr after administration of cysteamine (280 mg/ kg, p.o.). From various laboratories (22)(23)(24)(25)(26)(27) it was reported that cysteamine at the ulcerogenic dose significantly increased gastric H+ secretion within 1-4 hr in acute or chronic fistula rats, thereby suggesting the close link of increased gastric secretion in the pathogenesis. We also found that cysteamine (100 mg/kg) increased gastric H+ output by about 2-fold of the control values beginning from 2 hr after administration for the following 2 hr.…”