CELL-CYCLE PROGRESSION DURING GASTRIC-ULCER HEALING BY EBROTIDINE ANDSUCRALFATE

1. The effect of antiulcer agents, ebrotidine and sucralfate, on the e xpression of gastric mucosal proliferating cell nuclear antigen (PCNA) and cyclin-dependent kinase (p34Cdk2) during chronic ulcer healing wa s examined. 2. Rats with experimentally induced gastric ulcers were tr eated twice daily for 14 days with either ebrotidine at 100 mg/kg, suc ralfate at 100 mg/kg or vehicle, and at different stages of treatment their stomachs were used for quantitization of gastric mucosal PCNA an d Cdk2 expression. 3. The assays revealed that the ulcer healing was a ccompanied by a marked elevation in mucosal expression of PCNA and Cdk 2. The maximum increase in PCNA (4.7-fold) occurred by the second day of healing, and the expression of Cdk2 reached a maximum increase (2.3 -fold) by the fourth day. 4. Accelerated ulcer healing with ebrotidine (7 days) and sucralfate (8 days) treatments was reflected in a signif icant enhancement of PCNA and Cdk2 expression. By the second day of tr eatment, ebrotidine evoked a 15-fold increase in PCNA expression, and sucralfate produced an 11.8-fold enhancement. The mucosal expression o f Cdk2 attained a maximum of 4.3-fold increase over that of the contro ls by the sixth day of healing with ebrotidine, and a fivefold increas e in Cdk2 expression occurred by the fourth day of ulcer treatment wit h sucralfate. 5. The findings implicate eel cycle regulatory proteins in the processes leading to mucosal repair and suggest that the two dr ugs exert a similar effect on the expression of proteins that control cell cycle progression. (C) 1997 Elsevier Science Inc.