A fall in duodenal PGE2 synthesis precedes histological changes and ulceration in the cysteamine model of duodenal ulceration.

The temporal association of histological damage and mucosal prostaglandin E2 (PGE2) synthesis was examined in the cysteamine model of duodenal ulceration in the rat. Four groups of 10 animals were used; a control group (which had a light ether anaesthetic, an i.m. injection of vehicle and were killed 18 h later) and three treatment groups (which were similarly treated but injected with cysteamine (0.3 mg/g body weight) and killed at 6, 18 or 24 h). Estimates of duodenal PGE2 synthesis and histological assessment of mucosal damage were performed. There were four early deaths in the 24-h group due to intra-thoracic haemorrhage. The 6-h group appeared normal macroscopically. There were seven established and three early ulcers in the 18-h group and two established and four early ulcers in the survivors of the 24-h group. Microscopically, the 6-h group did not differ from controls, but the 18 and 24-h groups showed evidence of mucosal damage compared to the control group (P less than 0.001). All three treatment groups synthesized less PGE2 than did the control group (P less than 0.001). Thus at 6-h post-injection, a decrease in PGE2 synthesis was evident but mucosal damage occurred later. Histological features correlated negatively with PGE2 synthesis (P less than 0.001).